BACKGROUND AND OBJECTIVES

Low enrollment within pediatric research increases the cost of research, decreases generalizability, and threatens to exacerbate existing health disparities. To assess barriers and facilitators to pediatric research participation and evaluate differences by enrollment status.

METHODS

Data Sources include PubMed, Embase, PsycInfo, Cumulative Index to Nursing and Allied Health Literature, and Web of Science. Study selection include peer reviewed articles that contained information related to facilitators and barriers to the parental decision whether to enroll their child in research and included the views of parents who declined. We extracted barriers and facilitators to research, enrollment status, and study characteristics, including study design, quality, and patient population.

RESULTS

Seventy articles were included for analysis. Facilitators of participation included: benefits, trust, support of research, informational and consent related, and relational issues. Common facilitators within those categories included health benefit to child (N = 39), altruism (N = 30), and the importance of research (N = 26). Barriers to participation included: study-related concerns, burdens of participation, lack of trust, general research concerns, informational and consent related, and relational issues. Common barriers within those categories included risks to child (N = 46), burdens of participation (N = 35), and the stress of the decision (N = 29). We had a limited ability to directly compare by enrollment status and no ability to analyze interactions between facilitators and barriers. We only included studies written in English.

CONCLUSIONS

This review identified key facilitators and barriers to research participation in pediatrics. The findings from this review may guide researchers aiming to create interventions to improve the parental experience of recruitment for pediatric studies and to optimize enrollment rates.

Recruitment difficulties are common within clinical research, including within pediatrics. Enrollment challenges are documented within pediatric psychiatry,1  pediatric pain medicine,2  pediatric surgery subspecialties,3  neonatology,4,5  and in rural pediatric settings.6  Recruitment within pediatrics has additional challenges. Parents often serve as proxy decision-makers for children who cannot consent7,8  and the vulnerability of sick infants and children may be perceived differently than the vulnerability of adult patients.9  Many pediatric trials have enrollment windows that are very short and occur during times of high stress for children and parents.1012 

Low enrollment rates negatively impact clinical research in a variety of ways. Low enrollment increases the cost of conducting research13  and decreases generalizability because those who enroll are different from those who do not enroll in research. Rich and colleagues found that there were differences in baseline clinical characteristics by enrollment status, with sicker babies being less likely to be enrolled in neonatal research.14  Challenges recruiting under-represented populations for research have been well documented in multiple disciplines,15  and lower enrollment rates for Black infants, compared with white infants, have been found within some neonatal clinical trials.16,17  Lower participation of under-represented groups threatens to exacerbate existing pediatric health disparities.18,19 

Information about how parents decide whether to enroll their child in clinical research is lacking. Data are often hypothetical (eg, a study that asks parents if they would have enrolled their child had they been asked to participate in a clinical trial), which may not be generalizable.20  Much relevant work has struggled to include the views of those who decline,21,22  though a few manuscripts have successfully included the views of decliners.16,2325  Learning from parents who decline participation in pediatric research is critical if we aim to have a more representative research population and subsequently a more valid and generalizable evidence base. Therefore, we identified the need for a review of published manuscripts that describe the views of parents who declined pediatric research.

Prior reviews in this area reported only subsets of pediatric trials. Tromp evaluated motivating and discouraging factors to research participation but was exclusive to drug trials.26  Fisher’s narrative synthesis reported only qualitative studies.27 

In this manuscript, we focus on facilitators and barriers to pediatric research participation. We also report differences in these facilitators and barriers by enrollment status. Our review adds to the literature in at least 3 ways. First, it only includes parents who were genuinely asked to enroll their child in research. Second, it only includes studies that obtained the views of research decliners. These choices were made to increase external validity, as studies reporting the views of parents asked hypothetical questions about research and studies reporting views only of parents who chose to participate in research may be heavily biased. Third, it includes studies regardless of methodology, which enables a broader picture of the landscape within pediatric research.

Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines were followed28  and we submitted our proposal to Prospero,29  an online database where systematic review protocols are registered.

We searched for peer reviewed articles, written in English, that assessed facilitators and barriers to participation among parents asked to participate in pediatric research. Because the views of decliners are of particular importance, we only included studies that reported the views of some parents who had declined research.

A research librarian performed the search using 5 databases: PubMed, Embase, PsycInfo, Cumulative Index to Nursing and Allied Health Literature, and Web of Science (Fig 1). Duplicate results were removed, and all titles and abstracts were reviewed for relevance. Selected articles were read and reviewed using our inclusion and exclusion criteria. Additional articles were identified through snowballing and citation tracking. The PRISMA flow diagram (Fig 2) shows the process of study selection.

FIGURE 1

Overview of databases searched, search strings, and search results of articles identified.

FIGURE 1

Overview of databases searched, search strings, and search results of articles identified.

Close modal
FIGURE 2

PRISMA flow diagram of study identification, screening, selection, and inclusion.

FIGURE 2

PRISMA flow diagram of study identification, screening, selection, and inclusion.

Close modal

Two authors (T.O., and J.N.) independently conducted the screening of abstracts and review of full texts for inclusion or exclusion. Any discrepancies were discussed and agreed upon through group consensus.

Studies met inclusion criteria if they were peer reviewed articles, contained information about the parental decision whether to enroll their child in research and included parents who declined to enroll their child in pediatric research. Studies published before our search date of July 8, 2020 were eligible for inclusion.

Studies were excluded if they were hypothetical studies (eg, asked “would you enroll your child in such a study?”), did not include decliners, did not include parental views, did not take place in a medical setting, or did not include empirical data.

We used the Critical Appraisal Skills Program tool (Table 1) to assess qualitative studies30  and the Hawker tool (Table 2) to rate quality of each quantitative study.31  Following Cavolo, we assigned each category score and then assigned a summative “overall assessment” of low, moderate, or high.32  When a manuscript used mixed methods, quality was assessed based on the predominant methodology. Articles were not excluded based on quality assessment.

TABLE 1

Qualitative Quality Assessment: Critical Appraisal Skills Programme

Appraisal QuestionScoring
Clear statement of aims 1–3a 
Appropriate methodology 1–3 
Appropriate design 1–3 
Appropriate recruitment strategy 1–3 
Appropriate data collection 1–3 
Adequate consideration of the relationship between researcher and participants 1–3 
Ethical issues considered 1–3 
Data analysis sufficiently rigorous 1–3 
Clear statement of findings 1–3 
Was the research valuable 1–3 
Overall assessment 10–30b 
Appraisal QuestionScoring
Clear statement of aims 1–3a 
Appropriate methodology 1–3 
Appropriate design 1–3 
Appropriate recruitment strategy 1–3 
Appropriate data collection 1–3 
Adequate consideration of the relationship between researcher and participants 1–3 
Ethical issues considered 1–3 
Data analysis sufficiently rigorous 1–3 
Clear statement of findings 1–3 
Was the research valuable 1–3 
Overall assessment 10–30b 
a

 Yes = 3 points, unclear= 2 points, no = 1 point.

b

 High = 25 to 30 points, moderate = 20 to 24 points, low = 15 to 19 points, very low = 10 to 14 points.

TABLE 2

Quantitative Quality Assessment- Hawker

Appraisal QuestionScoring
Abstract and title 1–4a 
Introduction and aims 1–4 
Method and data 1–4 
Sampling 1–4 
Data analysis 1–4 
Ethics and bias 1–4 
Results 1–4 
Transferability or generalizability 1–4 
Implications and usefulness 1–4 
Overall assessment 9–36b 
Appraisal QuestionScoring
Abstract and title 1–4a 
Introduction and aims 1–4 
Method and data 1–4 
Sampling 1–4 
Data analysis 1–4 
Ethics and bias 1–4 
Results 1–4 
Transferability or generalizability 1–4 
Implications and usefulness 1–4 
Overall assessment 9–36b 
a

 Good = 4 points, fair = 3 points, poor = 2 points, very poor = 1 point.

b

 High = 31 to 36 points, moderate = 25 to 30 points, low = 20 to 24 points, very low = 9 to 19 points.

Each manuscript included in our review, hereafter called enrollment study, reported the parental views related to enrollment within 1 or more pediatric research studies, hereafter called feeder study. We collected basic information about the feeder study (or studies) referenced by each of the included manuscripts: design, target disease, clinical setting, and geographic location.

Data collected from the enrollment study included study characteristics, number of those who enrolled and those who declined, nature of underlying parent study, and information collection methods. The main measures were barriers and facilitators to participation in pediatric clinical research with an emphasis on the reasons parents decline to enroll their child.

We noted varied terminology used by manuscripts, which sometimes have meaningful differences and sometimes do not. Here we will use “enrolled” and “declined.” We also recognize that families are heterogeneous and do not always consist of a “parent.” However, the term parent was used consistently in the literature, and we will use that term in this review as well to mean parent, guardian, or caregiver.

We double-coded the initial 10 manuscripts. Interrater reliability assessment identified substantial agreement for categorization of facilitators (κ coefficient 0.755) and almost perfect agreement for categorization of barriers (κ coefficient 0.876). Evaluation of the discrepancies revealed that the majority of differences were because of subcategory categorization rather than missed factors. As the agreement was high, we proceeded with data extraction performed by only a single person. We double coded 10% of the manuscripts to confirm consistency of our process, which revealed continued substantial to perfect agreement for categorization of items. We also flagged any manuscripts with data particularly challenging to be double-coded. Discrepancies or uncertain placements were adjudicated through group consensus.

For each facilitator or barrier to enrollment, we extracted whether an enrollment study identified the item and then whether it compared differences in that item by enrollment status (eg, enrolled versus declined).

We identified 17 924 articles from our initial literature search. Duplicates and comment only results were removed. Articles that were reviewed based on title and abstract include 9889 articles and 293 articles were then reviewed in full, resulting in 68 articles meeting inclusion criteria. Two additional articles were added after snowballing and tracking, resulting in 70 articles included in this systematic review (Fig 2).22,24,3399 

Table 3 shows an overview of the characteristics of the 70 included studies. Most feeder studies were clinical trials (N = 47), the majority of which were drug studies. Both outpatient (N = 44) and inpatient (N = 33) feeder studies were represented, including representation of intensive care units (N = 17). Feeder studies included research from many countries. Enrollment studies included quantitative, qualitative, and mixed methodologies. Most common approaches were surveys (N = 32), interviews (N = 28), and secondary analyses of previously collected data, such as from recruitment logs (N = 15).

TABLE 3

Overview of Included Studies

StudySummaryData Type of ESQuality Assessment of ESDesign of FSDisease or system in FSSetting of FSCountry of FS
Barakat 201433  Parents of children with cancer approached for multiple phase 3 clinical drug trials Qualitative interview 28 (High) Clinical trial: drug study Oncology Outpatient United States 
Bartlett 201834  Parents of infants with SMA and parents of infants without SMA approached to participate in an observational biomarker study Quantitative survey 31 (High) Observational Neurology Outpatient United States 
Baxter 201235  Parents of HLA positive infants approached to participate in a study tracking environmental determinants of T1DM Quantitative secondary analysis 33 (High) Observational Diabetes Outpatient United States, Finland, Germany, and Sweden 
Braga 201436  Parents of infants with hydronephrosis approached for a trial to determine if continuous antibiotic prophylaxis would prevent UTI Quantitative (not specified) 31 (High) Clinical trial: drug study Renal Outpatient Canada 
Buck 201537  Parents of children with intermittent exotropia were approached for a study comparing the effectiveness of surgery versus active monitoring Qualitative interview and secondary analysis 25 (High) Clinical trial: nondrug study Surgery and ophthalmology Outpatient United Kingdom 
Chantler 200738  Parents of preschool children were approached to participate in 1 of 2 vaccine studies (meningitis or diphtheria) Qualitative interview 25 (High) Clinical trial: vaccine study General pediatrics Outpatient United Kingdom 
Chappuy 200639  Parents of children with either cancer or HIV approached to enroll their child in 1 of several clinical trials Quantitative survey 30 (Moderate) Clinical trial: nondrug study Infectious diseases and oncology Outpatient and ED France 
Clausen 195440  Mothers of second grade students approached to participate in a vaccine study Quantitative survey and interview 29 (Moderate) Clinical trial: vaccine study General pediatrics Outpatient United States 
D'Amanda 201941  Parents of children with Fragile X Syndrome approached for 1 of several drug studies Qualitative interview 27 (High) Clinical trial: drug study Fragile X syndrome Outpatient United States 
Dahan 202022  Parents of newborns in the NICU at risk for intubation approached to participate in an anesthesia trial Quantitative interview 30 (moderate) Clinical trial: nondrug study Anesthesia NICU France 
Dlugos 200542  Parents of children with epilepsy approached to participate in a study on the genetic influences of epilepsy Quantitative interview and secondary analysis 30 (Moderate) Observational Neurology Outpatient United States 
Dreyzin 201443  Parents of children with acute hepatic failure approached for 1 study evaluating the effectiveness of hepatocyte growth factor Qualitative interview 24 (Moderate) Clinical trial: nondrug study Gastrointestinal Outpatient United States 
Eiser 200544  Parents of children with ALL approached for 4 quality of life studies Qualitative interview 15 (Low) Clinical trial: drug study Oncology Outpatient and inpatient United Kingdom 
Elemraid 201345  Parents of children with pneumonia or empyema approached for 3 studies for analysis of blood, urine, and respiratory secretions Qualitative secondary analysis 23 (Moderate) Observational Pulmonary Inpatient United Kingdom 
Gattuso 200646  Parents of children with cancer approached for ten nontherapeutic behavioral medicine studies Quantitative secondary analysis 31 (High) Clinical trial and observational Oncology Outpatient and inpatient United Kingdom 
Genetti 201947  Parents of newborns approached to participate in a whole genomics sequencing study Quantitative survey and secondary analysis 32 (High) Genome sequencing Well newborn and genetics Inpatient pediatric floor and NICU United States 
Gill 201448  Parents of children in cardiology, orthopedics, surgical day unit, or ED approached for 15 different nondrug trials Quantitative survey 33 (High) Clinical trial and observational General pediatrics, cardiology, anesthesia, surgery, and orthopedics Outpatient, ED, inpatient, and OR11  Canada 
Gonzalez 201649  Parents of children approached to participate in several studies comparing 2 different treatments or procedures Quantitative survey 29 (Moderate) Clinical trial: nondrug study General pediatrics, gastrointestinal, and surgery OR United States 
Greenberg 201750  Parents of children with 13 different medical conditions approached for a wide variety of interventional and non-interventional studies Qualitative interview 26 (High) Observational and clinical trial: drug study Not specified Outpatient and NICU United States 
Harth 199051  Parents of children with asthma approached for a new drug study Quantitative survey 31 (High) Clinical trial: drug study Asthma Outpatient and inpatient Australia 
Harth 199252  Parents of children with asthma approached for a study about behavior and personality Quantitative personality tests 34 (High) Clinical trial: drug study Asthma Outpatient and inpatient Australia 
Hayman 200153  Parents of healthy newborns who had been offered enrollment in 1 of 2 SIDS trials Quantitative survey 31 (High) Observational Well newborn Maternity unit New Zealand 
Helgesson 200954  Parents of healthy children approached for a longitudinal study on the environmental and genetic risk factors of T1DM Quantitative survey 32 (High) Observational Diabetes Outpatient Sweden 
Hoberman 201355  Parents of children with vesicoureteral reflex approached to enroll in a drug trial Quantitative survey 33 (High) Clinical trial: drug study Vesicoureteral reflex Outpatient and inpatient United States 
Hoehn 200556  Parents of neonates with congenital heart disease approached for 1 of 5 various clinical trials Qualitative interview 24 (Moderate) Observational and clinical trial: nondrug study Cardiovascular OR United States 
Hoehn 200957  Parents of children with congenital heart disease approached for 1 of 3 observational studies Qualitative interview 22 (moderate) Observational Cardiovascular Outpatient, inpatient, and OR United States 
Howard Sharp 202058  Parents of children approached to enroll their child in a genome study examining the feasibility of clinical genomic analysis Quantitative secondary analysis 34 (High) Genome sequencing Oncology Outpatient and inpatient United States 
Hulst 200559  Parents of neonates and children approached for a nutritional study following intensive care admission Quantitative secondary analysis 33 (High) Clinical trial: nondrug study Nutritional NICU, PICU Netherlands 
Ingersgaard 201860  Parents of children with ALL approached for1 of 2 drug trials Qualitative interview 27 (High) Clinical trial: drug study Oncology Outpatient Denmark 
Jay 200761  Parents of healthy preschool children approached to participate in long-term vaccine protection trial Quantitative survey 30 (Moderate) Observational General pediatrics Outpatient United Kingdom 
Jenkins 200962  Mothers of children with and without birth defects approached to participate in the National Birth Defect Study on genetic and environmental risks Qualitative interview 27 (High) Observational General pediatrics Outpatient United States 
Jollye 200963  Parents of newborns approached to participate in 1 of 3 nonurgent clinical NICU trials Qualitative interview 24 (Moderate) Clinical trial: nondrug study Neonatology NICU United Kingdom 
Kick 201864  Parents of children with T1DM autoantibodies, but with normal glucose tolerance test, approached to participate in the FR1DA insulin intervention study Quantitative interview 33 (High) Clinical trial: drug study Diabetes Outpatient Germany 
Korotchikova 201065  Parents of healthy newborns approached to participate in an EEG study Quantitative secondary analysis 33 (High) Observational Well newborn Maternity unit Ireland 
Kumari 201966  Parents of children with autism or intellectual disability approached to enroll in a genetic testing study Quantitative survey 33 (High) Observational Autism Outpatient India 
Labib 201867  Parents of children with cancer approached to contribute samples to a biobank Quantitative survey 33 (High) Observational Oncology Inpatient Egypt 
Langley 199868  Parents of healthy infants approached to enroll in 1 of 2 pertussis vaccine trials Quantitative survey 34 (High) Clinical trial: vaccine study General pediatrics Outpatient Canada 
Mason 200069  Parents of infants approached to participate in 1 of several NICU trials Quantitative interview 32 (High) Clinical trial: drug and nondrug studies Neonatology NICU nine European countries 
Mazzocco 199970  Parents of children with Fragile X syndrome approached for 1 of 2 genetic studies Quantitative survey 29 (Moderate) Observational Fragile X syndrome Outpatient United States 
Menon 201271  Parents of children in the PICU approached for 45 different studies Quantitative observation 36 (High) Observational and clinical trial Not specified PICU Canada 
Menon 201472  Parents of children with invasive lines approached for 1 study looking at clinical outcomes following ACTH stimulation Quantitative secondary analysis 34 (High) Clinical trial: drug study Renal PICU Canada 
Mihrshahi 200273  Mothers with a history of asthma approached to enroll their newborn in an asthma prevention study Quantitative secondary analysis 35 (High) Clinical trial: nondrug study General pediatrics Outpatient Australia 
Morley 200574  Parents of premature infants approached to enroll in multiple clinical trials Quantitative survey 32 (High) Observational and clinical trial Premature infants NICU Australia 
Mwangi 201775  Mothers of healthy children approached for a malaria prevention drug trial Qualitative interview 30 (High) Clinical trial: drug study Well newborn and infectious disease Outpatient Tanzania 
Nieminen 201576  Parents of children approached to enroll in a pneumococcal vaccine trial Quantitative survey 35 (High) Clinical trial: vaccine study General pediatrics Outpatient Finland 
Norris 201077  Parents of children with AN or EDNOS with BMI < 17.5kg/m2 approached for an antipsychotic drug trial Quantitative survey 29 (Moderate) Clinical trial: drug study Psychiatric Outpatient Canada 
Pagano-Therrien 201778  Parents of children with chronic health conditions approached for multiple trials Qualitative interview 29 (High) Clinical trial and observational Cystic fibrosis, T1DM, and HIV Outpatient United States 
Papaz 201279  Parents of children with heart disease approached to donate samples to the heart center biobank registry Quantitative secondary analysis 33 (High) Biorepository Cardiovascular Outpatient and inpatient Canada 
Paquette 201980  Parents of children in the PICU approached for 1 of 8 different studies Quantitative survey 32 (High) Multiple feeder studies Not specified PICU United States 
Read 200981  Parents of children with cancer approached to participate in multiple cancer drug trials Quantitative survey 33 (High) Clinical trial: drug study Oncology Outpatient Canada 
Sammons 200782  Parents of children with pneumonia approached to participate in a study comparing 2 different antibiotics Quantitative survey 29 (Moderate) Clinical trial: drug study Infectious disease Inpatient United Kingdom 
Scollon 201483  Parents of children with solid tumors approached to participate in a whole genome sequencing study Quantitative secondary analysis 35 (High) Genome sequencing Oncology Outpatient United States 
Shah 201823  Parents of premature infants approached to participate in a drug trial of EPO Quantitative survey and interview 36 (High) Clinical trial: drug study Neonatology NICU United States 
Shilling 200984  Parents of children with various illnesses approached for a variety of drug studies Quantitative interview 34 (High) Clinical trial: drug study Asthma, neurology, and rheumatic diseases Outpatient and NICU United Kingdom 
Skinner 201185  Parents of healthy newborns approached to enroll for genetic screening of Fragile X syndrome Quantitative survey 36 (High) Genetic screening Fragile X syndrome Maternity unit United States 
Snowdon 200686  Parents of preterm infants approached to participate in 1 of 4 clinical drug trials Qualitative interview 27 (High) Clinical trial: drug study Neonatology NICU Canada 
Sureshkumar 201287  Parents of children with symptomatic UTI were approached for a UTI preventing drug study Quantitative survey 34 (High) Clinical trial: drug study Urogynecology Outpatient and ED Australia 
Surun 201888  Parents of children with cancer who entered palliative care were approached for a phase 1 or phase 2 drug trial Quantitative secondary analysis 33 (High) Clinical trial: drug study Oncology Outpatient and inpatient France 
Tait 199891  Parents of children undergoing surgery were approached to participate in several anesthesia trials Quantitative survey 30 (Moderate) Observational and clinical trial Anesthesia OR United States 
Tait 200389  Parents of children undergoing surgery were approached to participate in 1 of 18 anesthesia or surgical clinical trials Quantitative survey and interview 35 (High) Observational and clinical trial: drug study Anesthesia and surgery OR United States 
Tait 200490  Parents of children scheduled for surgery approached for various anesthesia or surgical clinical trials Quantitative survey 33 (High) Observational and clinical trial Anesthesia and surgery OR United States 
Taylor 201592  Parents of children approached for 40 various studies in the emergency department Quantitative secondary analysis 35 (High) Observational and clinical trial Not specified ED United States 
Thomas 201393  Parents of children in the PICU approached to participate in 1 of multiple critical care studies Qualitative interview 29 (High) Observational and clinical trial Critical care PICU Canada 
Vecchi 201394  Mothers of newborns approached for 1 study assessing neurodevelopment and mercury exposure Quantitative survey 36 (High) Observational Well newborn Outpatient Italy 
Volkening 201795  Mothers of healthy newborns approached for a cohort study on mercury exposure and child neurodevelopment Quantitative survey 33 (High) Newborn cohort study Well newborn Outpatient Italy 
Ward 200996  Parents of neonates approached for multiple clinical trials with more than minimal risk Qualitative interview 30 (High) Clinical trial: nondrug study Neonatology PICU United States 
Woodgate 201097  Parents of children with cancer approached for 1 of many clinical trials Qualitative interview 28 (High) Clinical trial Oncology Outpatient Canada 
Woolfall 201398  Parents of children with various illness approached to enroll in 1 of 4 clinical trials Qualitative interview 30 (High) Clinical trial: drug study Asthma, neurology, rhematic disease, and neonatology Outpatient and NICU United Kingdom 
Wynn 201099  Parents of children with sickle cell disease approached to participate in a hydroxyurea drug trial Quantitative survey 28 (moderate) Clinical trial: drug study Hematology Outpatient United States 
Zupancic 199724  Parents of newborns in the NICU approached to participate in 1 of 3 clinical drug trials Quantitative survey 33 (High) Clinical trial: drug study Neonatology PICU Canada 
StudySummaryData Type of ESQuality Assessment of ESDesign of FSDisease or system in FSSetting of FSCountry of FS
Barakat 201433  Parents of children with cancer approached for multiple phase 3 clinical drug trials Qualitative interview 28 (High) Clinical trial: drug study Oncology Outpatient United States 
Bartlett 201834  Parents of infants with SMA and parents of infants without SMA approached to participate in an observational biomarker study Quantitative survey 31 (High) Observational Neurology Outpatient United States 
Baxter 201235  Parents of HLA positive infants approached to participate in a study tracking environmental determinants of T1DM Quantitative secondary analysis 33 (High) Observational Diabetes Outpatient United States, Finland, Germany, and Sweden 
Braga 201436  Parents of infants with hydronephrosis approached for a trial to determine if continuous antibiotic prophylaxis would prevent UTI Quantitative (not specified) 31 (High) Clinical trial: drug study Renal Outpatient Canada 
Buck 201537  Parents of children with intermittent exotropia were approached for a study comparing the effectiveness of surgery versus active monitoring Qualitative interview and secondary analysis 25 (High) Clinical trial: nondrug study Surgery and ophthalmology Outpatient United Kingdom 
Chantler 200738  Parents of preschool children were approached to participate in 1 of 2 vaccine studies (meningitis or diphtheria) Qualitative interview 25 (High) Clinical trial: vaccine study General pediatrics Outpatient United Kingdom 
Chappuy 200639  Parents of children with either cancer or HIV approached to enroll their child in 1 of several clinical trials Quantitative survey 30 (Moderate) Clinical trial: nondrug study Infectious diseases and oncology Outpatient and ED France 
Clausen 195440  Mothers of second grade students approached to participate in a vaccine study Quantitative survey and interview 29 (Moderate) Clinical trial: vaccine study General pediatrics Outpatient United States 
D'Amanda 201941  Parents of children with Fragile X Syndrome approached for 1 of several drug studies Qualitative interview 27 (High) Clinical trial: drug study Fragile X syndrome Outpatient United States 
Dahan 202022  Parents of newborns in the NICU at risk for intubation approached to participate in an anesthesia trial Quantitative interview 30 (moderate) Clinical trial: nondrug study Anesthesia NICU France 
Dlugos 200542  Parents of children with epilepsy approached to participate in a study on the genetic influences of epilepsy Quantitative interview and secondary analysis 30 (Moderate) Observational Neurology Outpatient United States 
Dreyzin 201443  Parents of children with acute hepatic failure approached for 1 study evaluating the effectiveness of hepatocyte growth factor Qualitative interview 24 (Moderate) Clinical trial: nondrug study Gastrointestinal Outpatient United States 
Eiser 200544  Parents of children with ALL approached for 4 quality of life studies Qualitative interview 15 (Low) Clinical trial: drug study Oncology Outpatient and inpatient United Kingdom 
Elemraid 201345  Parents of children with pneumonia or empyema approached for 3 studies for analysis of blood, urine, and respiratory secretions Qualitative secondary analysis 23 (Moderate) Observational Pulmonary Inpatient United Kingdom 
Gattuso 200646  Parents of children with cancer approached for ten nontherapeutic behavioral medicine studies Quantitative secondary analysis 31 (High) Clinical trial and observational Oncology Outpatient and inpatient United Kingdom 
Genetti 201947  Parents of newborns approached to participate in a whole genomics sequencing study Quantitative survey and secondary analysis 32 (High) Genome sequencing Well newborn and genetics Inpatient pediatric floor and NICU United States 
Gill 201448  Parents of children in cardiology, orthopedics, surgical day unit, or ED approached for 15 different nondrug trials Quantitative survey 33 (High) Clinical trial and observational General pediatrics, cardiology, anesthesia, surgery, and orthopedics Outpatient, ED, inpatient, and OR11  Canada 
Gonzalez 201649  Parents of children approached to participate in several studies comparing 2 different treatments or procedures Quantitative survey 29 (Moderate) Clinical trial: nondrug study General pediatrics, gastrointestinal, and surgery OR United States 
Greenberg 201750  Parents of children with 13 different medical conditions approached for a wide variety of interventional and non-interventional studies Qualitative interview 26 (High) Observational and clinical trial: drug study Not specified Outpatient and NICU United States 
Harth 199051  Parents of children with asthma approached for a new drug study Quantitative survey 31 (High) Clinical trial: drug study Asthma Outpatient and inpatient Australia 
Harth 199252  Parents of children with asthma approached for a study about behavior and personality Quantitative personality tests 34 (High) Clinical trial: drug study Asthma Outpatient and inpatient Australia 
Hayman 200153  Parents of healthy newborns who had been offered enrollment in 1 of 2 SIDS trials Quantitative survey 31 (High) Observational Well newborn Maternity unit New Zealand 
Helgesson 200954  Parents of healthy children approached for a longitudinal study on the environmental and genetic risk factors of T1DM Quantitative survey 32 (High) Observational Diabetes Outpatient Sweden 
Hoberman 201355  Parents of children with vesicoureteral reflex approached to enroll in a drug trial Quantitative survey 33 (High) Clinical trial: drug study Vesicoureteral reflex Outpatient and inpatient United States 
Hoehn 200556  Parents of neonates with congenital heart disease approached for 1 of 5 various clinical trials Qualitative interview 24 (Moderate) Observational and clinical trial: nondrug study Cardiovascular OR United States 
Hoehn 200957  Parents of children with congenital heart disease approached for 1 of 3 observational studies Qualitative interview 22 (moderate) Observational Cardiovascular Outpatient, inpatient, and OR United States 
Howard Sharp 202058  Parents of children approached to enroll their child in a genome study examining the feasibility of clinical genomic analysis Quantitative secondary analysis 34 (High) Genome sequencing Oncology Outpatient and inpatient United States 
Hulst 200559  Parents of neonates and children approached for a nutritional study following intensive care admission Quantitative secondary analysis 33 (High) Clinical trial: nondrug study Nutritional NICU, PICU Netherlands 
Ingersgaard 201860  Parents of children with ALL approached for1 of 2 drug trials Qualitative interview 27 (High) Clinical trial: drug study Oncology Outpatient Denmark 
Jay 200761  Parents of healthy preschool children approached to participate in long-term vaccine protection trial Quantitative survey 30 (Moderate) Observational General pediatrics Outpatient United Kingdom 
Jenkins 200962  Mothers of children with and without birth defects approached to participate in the National Birth Defect Study on genetic and environmental risks Qualitative interview 27 (High) Observational General pediatrics Outpatient United States 
Jollye 200963  Parents of newborns approached to participate in 1 of 3 nonurgent clinical NICU trials Qualitative interview 24 (Moderate) Clinical trial: nondrug study Neonatology NICU United Kingdom 
Kick 201864  Parents of children with T1DM autoantibodies, but with normal glucose tolerance test, approached to participate in the FR1DA insulin intervention study Quantitative interview 33 (High) Clinical trial: drug study Diabetes Outpatient Germany 
Korotchikova 201065  Parents of healthy newborns approached to participate in an EEG study Quantitative secondary analysis 33 (High) Observational Well newborn Maternity unit Ireland 
Kumari 201966  Parents of children with autism or intellectual disability approached to enroll in a genetic testing study Quantitative survey 33 (High) Observational Autism Outpatient India 
Labib 201867  Parents of children with cancer approached to contribute samples to a biobank Quantitative survey 33 (High) Observational Oncology Inpatient Egypt 
Langley 199868  Parents of healthy infants approached to enroll in 1 of 2 pertussis vaccine trials Quantitative survey 34 (High) Clinical trial: vaccine study General pediatrics Outpatient Canada 
Mason 200069  Parents of infants approached to participate in 1 of several NICU trials Quantitative interview 32 (High) Clinical trial: drug and nondrug studies Neonatology NICU nine European countries 
Mazzocco 199970  Parents of children with Fragile X syndrome approached for 1 of 2 genetic studies Quantitative survey 29 (Moderate) Observational Fragile X syndrome Outpatient United States 
Menon 201271  Parents of children in the PICU approached for 45 different studies Quantitative observation 36 (High) Observational and clinical trial Not specified PICU Canada 
Menon 201472  Parents of children with invasive lines approached for 1 study looking at clinical outcomes following ACTH stimulation Quantitative secondary analysis 34 (High) Clinical trial: drug study Renal PICU Canada 
Mihrshahi 200273  Mothers with a history of asthma approached to enroll their newborn in an asthma prevention study Quantitative secondary analysis 35 (High) Clinical trial: nondrug study General pediatrics Outpatient Australia 
Morley 200574  Parents of premature infants approached to enroll in multiple clinical trials Quantitative survey 32 (High) Observational and clinical trial Premature infants NICU Australia 
Mwangi 201775  Mothers of healthy children approached for a malaria prevention drug trial Qualitative interview 30 (High) Clinical trial: drug study Well newborn and infectious disease Outpatient Tanzania 
Nieminen 201576  Parents of children approached to enroll in a pneumococcal vaccine trial Quantitative survey 35 (High) Clinical trial: vaccine study General pediatrics Outpatient Finland 
Norris 201077  Parents of children with AN or EDNOS with BMI < 17.5kg/m2 approached for an antipsychotic drug trial Quantitative survey 29 (Moderate) Clinical trial: drug study Psychiatric Outpatient Canada 
Pagano-Therrien 201778  Parents of children with chronic health conditions approached for multiple trials Qualitative interview 29 (High) Clinical trial and observational Cystic fibrosis, T1DM, and HIV Outpatient United States 
Papaz 201279  Parents of children with heart disease approached to donate samples to the heart center biobank registry Quantitative secondary analysis 33 (High) Biorepository Cardiovascular Outpatient and inpatient Canada 
Paquette 201980  Parents of children in the PICU approached for 1 of 8 different studies Quantitative survey 32 (High) Multiple feeder studies Not specified PICU United States 
Read 200981  Parents of children with cancer approached to participate in multiple cancer drug trials Quantitative survey 33 (High) Clinical trial: drug study Oncology Outpatient Canada 
Sammons 200782  Parents of children with pneumonia approached to participate in a study comparing 2 different antibiotics Quantitative survey 29 (Moderate) Clinical trial: drug study Infectious disease Inpatient United Kingdom 
Scollon 201483  Parents of children with solid tumors approached to participate in a whole genome sequencing study Quantitative secondary analysis 35 (High) Genome sequencing Oncology Outpatient United States 
Shah 201823  Parents of premature infants approached to participate in a drug trial of EPO Quantitative survey and interview 36 (High) Clinical trial: drug study Neonatology NICU United States 
Shilling 200984  Parents of children with various illnesses approached for a variety of drug studies Quantitative interview 34 (High) Clinical trial: drug study Asthma, neurology, and rheumatic diseases Outpatient and NICU United Kingdom 
Skinner 201185  Parents of healthy newborns approached to enroll for genetic screening of Fragile X syndrome Quantitative survey 36 (High) Genetic screening Fragile X syndrome Maternity unit United States 
Snowdon 200686  Parents of preterm infants approached to participate in 1 of 4 clinical drug trials Qualitative interview 27 (High) Clinical trial: drug study Neonatology NICU Canada 
Sureshkumar 201287  Parents of children with symptomatic UTI were approached for a UTI preventing drug study Quantitative survey 34 (High) Clinical trial: drug study Urogynecology Outpatient and ED Australia 
Surun 201888  Parents of children with cancer who entered palliative care were approached for a phase 1 or phase 2 drug trial Quantitative secondary analysis 33 (High) Clinical trial: drug study Oncology Outpatient and inpatient France 
Tait 199891  Parents of children undergoing surgery were approached to participate in several anesthesia trials Quantitative survey 30 (Moderate) Observational and clinical trial Anesthesia OR United States 
Tait 200389  Parents of children undergoing surgery were approached to participate in 1 of 18 anesthesia or surgical clinical trials Quantitative survey and interview 35 (High) Observational and clinical trial: drug study Anesthesia and surgery OR United States 
Tait 200490  Parents of children scheduled for surgery approached for various anesthesia or surgical clinical trials Quantitative survey 33 (High) Observational and clinical trial Anesthesia and surgery OR United States 
Taylor 201592  Parents of children approached for 40 various studies in the emergency department Quantitative secondary analysis 35 (High) Observational and clinical trial Not specified ED United States 
Thomas 201393  Parents of children in the PICU approached to participate in 1 of multiple critical care studies Qualitative interview 29 (High) Observational and clinical trial Critical care PICU Canada 
Vecchi 201394  Mothers of newborns approached for 1 study assessing neurodevelopment and mercury exposure Quantitative survey 36 (High) Observational Well newborn Outpatient Italy 
Volkening 201795  Mothers of healthy newborns approached for a cohort study on mercury exposure and child neurodevelopment Quantitative survey 33 (High) Newborn cohort study Well newborn Outpatient Italy 
Ward 200996  Parents of neonates approached for multiple clinical trials with more than minimal risk Qualitative interview 30 (High) Clinical trial: nondrug study Neonatology PICU United States 
Woodgate 201097  Parents of children with cancer approached for 1 of many clinical trials Qualitative interview 28 (High) Clinical trial Oncology Outpatient Canada 
Woolfall 201398  Parents of children with various illness approached to enroll in 1 of 4 clinical trials Qualitative interview 30 (High) Clinical trial: drug study Asthma, neurology, rhematic disease, and neonatology Outpatient and NICU United Kingdom 
Wynn 201099  Parents of children with sickle cell disease approached to participate in a hydroxyurea drug trial Quantitative survey 28 (moderate) Clinical trial: drug study Hematology Outpatient United States 
Zupancic 199724  Parents of newborns in the NICU approached to participate in 1 of 3 clinical drug trials Quantitative survey 33 (High) Clinical trial: drug study Neonatology PICU Canada 

ACTH, adrenocorticotropin hormone; ALL, acute lymphoblastic leukemia; AN, anorexia nervosa; ED, emergency department; EDNOS, eating disorder not otherwise specified; EPO, erythropoietin ES, enrollment study; FS, feeder study; OR, operating room; SIDS, sudden infant death syndrome; SMA, spinal muscular atrophy; T1DM, Type-1 diabetes mellitus; UTI, urinary tract infection.

Overall study quality of qualitative studies, using the Critical Appraisal Skills Programme tool,30  ranged from 15 (low) to 30 (high) with most studies scoring in the high category (25–30). Overall study quality of quantitative studies, using the Hawker tool,31  ranged from 28 (moderate) to 36 (high) with most studies scoring in the high category (31–36). Quality assessment was used to better understand the overall quality of the included studies; it was not used to exclude low scoring articles. Quality assessment scores are included in Table 3.

Because of heterogeneity in methodologies and terminologies, our team needed to create a schema of categories to generate meaningful comparisons between studies. This was done through literature review, prior work, and multiple rounds of reading manuscripts to reach consensus among the 3 authors. First, we distinguished between facilitators and barriers. Although some items were easy to categorize (eg, “perceived health benefit to child” as a facilitator), others were not straightforward. For example, it seemed clear that “additional travel to medical center” should be a barrier, which we included in “burdens of participation.” However, some manuscripts reported the “lack of additional burden for family” as a reason that parents cited as supporting research participation. We chose to always keep the framing of each item as presented in the manuscript, rather than reporting the inverse. See Tables 4 and 5 for our categories, the items within each category, definitions, and exemplary quotes.

TABLE 4

Definitions of Facilitators to Pediatric Research Participation

CategoryFacilitatorsDefinitionExample
Benefits Health benefit to child Direct health benefit to the child To have “the most advanced treatment available” (Chappuy 2006)39  
Non-health benefit to child A benefit to the child outside of health The child would be more “at ease with the home visits” provided by enrolling (Chantler 2007)38  
More contact with medical team More contact or time with medical team “Study staff contactable at any time to answer query” (Jay 2007)61  
Direct benefit to parent A direct benefit to the parent For the parent “to meet people” (Harth 1990)51  
Minimal burden to child or parent Minimal burden (eg, time or pain) to child or parent “No additional tests or hospital visits” for the child (Eiser 2005)44  
Financial reimbursement Financial reimbursement Reimbursement of travel costs (Harth 1990)51  
Trust Trust in clinician Trust in the clinician(s) Trust in the medical team (Chappuy 2006)39  
Trust in medical researchers Trust in medical researchers Trust that the researchers would not “purposely do something they think can harm babies” (Snowdon 2006)86  
Trust in particular institution Trust in a particular institution (eg, hospital or university) “Study proposed by an institution that I trust” (Vecchi 2013)94  
Trust in medicine in general Trust in medicine in general “Trust in the medical system” (Tait 2004)90  
Trust in research Trust in research or the safety of research “Trust in research” (Hoberman 2013)55  
Trust (other) Trust that did not fit into another category “Trust in vaccines” (Chantler 2007)38  
Support of research Altruism To benefit or help others “Other children might benefit” (Tait 1998)91  
Importance of medical research The importance of research or the importance of contribution to research To contribute to “medical research” (Harth 1990)51  
Informational and consent process related Felt as only option Felt as only option remaining to help the child Parents felt that there “were no available therapeutic alternatives” (Chappuy 2006)39  
Understanding of research materials Understanding of research materials (eg, consent documents) Understanding of the consent (Tait 2003)89  
Experience or lack of experience with research Past experience of lack of experience with medical research, including being enrolled in a different trial at the time “Prior experience with research” (Chappuy 2006)39  
Relational Positive relationship to researcher Positive relationship or experience with the team conducting the research The researchers were viewed as “friendly and relaxed” (Tait 2003)89  
Influence of family and friends Influence of family and friends “Felt pressure from my family or friends” (Read 2009)81  
Participation encouraged by clinical team Participation was encouraged by the child's clinical team “Doctor asked them to participate” (Sammons 2007)82  
Child's desire to participate Child's desire to participate in research “Child wanted to participate” (Paquette 2019)80  
CategoryFacilitatorsDefinitionExample
Benefits Health benefit to child Direct health benefit to the child To have “the most advanced treatment available” (Chappuy 2006)39  
Non-health benefit to child A benefit to the child outside of health The child would be more “at ease with the home visits” provided by enrolling (Chantler 2007)38  
More contact with medical team More contact or time with medical team “Study staff contactable at any time to answer query” (Jay 2007)61  
Direct benefit to parent A direct benefit to the parent For the parent “to meet people” (Harth 1990)51  
Minimal burden to child or parent Minimal burden (eg, time or pain) to child or parent “No additional tests or hospital visits” for the child (Eiser 2005)44  
Financial reimbursement Financial reimbursement Reimbursement of travel costs (Harth 1990)51  
Trust Trust in clinician Trust in the clinician(s) Trust in the medical team (Chappuy 2006)39  
Trust in medical researchers Trust in medical researchers Trust that the researchers would not “purposely do something they think can harm babies” (Snowdon 2006)86  
Trust in particular institution Trust in a particular institution (eg, hospital or university) “Study proposed by an institution that I trust” (Vecchi 2013)94  
Trust in medicine in general Trust in medicine in general “Trust in the medical system” (Tait 2004)90  
Trust in research Trust in research or the safety of research “Trust in research” (Hoberman 2013)55  
Trust (other) Trust that did not fit into another category “Trust in vaccines” (Chantler 2007)38  
Support of research Altruism To benefit or help others “Other children might benefit” (Tait 1998)91  
Importance of medical research The importance of research or the importance of contribution to research To contribute to “medical research” (Harth 1990)51  
Informational and consent process related Felt as only option Felt as only option remaining to help the child Parents felt that there “were no available therapeutic alternatives” (Chappuy 2006)39  
Understanding of research materials Understanding of research materials (eg, consent documents) Understanding of the consent (Tait 2003)89  
Experience or lack of experience with research Past experience of lack of experience with medical research, including being enrolled in a different trial at the time “Prior experience with research” (Chappuy 2006)39  
Relational Positive relationship to researcher Positive relationship or experience with the team conducting the research The researchers were viewed as “friendly and relaxed” (Tait 2003)89  
Influence of family and friends Influence of family and friends “Felt pressure from my family or friends” (Read 2009)81  
Participation encouraged by clinical team Participation was encouraged by the child's clinical team “Doctor asked them to participate” (Sammons 2007)82  
Child's desire to participate Child's desire to participate in research “Child wanted to participate” (Paquette 2019)80  
TABLE 5

Definitions of Barriers to Pediatric Research Participation

CategoryBarriersDefinitionExample
Concerns about study participation Risk to child Risk to child, including side-effects and safety concerns “Concerns about side-effects” (Buck 2015)37  
Negative impact on medical care Negative impact on medical care, including preference for the standard of care “Study would interfere with the standard care” (Hoberman 2013)55  
Lack of direct benefit to child Lack of a direct benefit to child “Drug was less likely to benefit their child” (D'Amanda 2019)41  
Child's own medical concerns Child's own medical concerns or knowledge “Child does not know true diagnosis” (Chappuy 2006)39  
Phlebotomy concerns Concerns with blood draws “Blood-draw requirements” mentioned as a barrier (D'Amanda 2019)41  
Burdens Logistics or burden of participation Logistics or burdens of participation (eg, travel, time, or money) “Excessive travel” (Bartlett 2018)34  
Lack of trust Lack of trust in clinicians Lack of trust in the clinicians “Poor confidence in physician” (Chappuy 2006)39  
Lack of trust in medical researchers Lack of trust in medical researchers “Distrust of researchers” (Mason 2000)69  
Lack of trust in particular institution Lack of trust in a particular institution (eg, hospital or university) “Distrust in the hospital” (Harth 1990)51  
Lack of trust in medicine in general Lack of trust in medicine in general “Distrust in modern medicine” (Harth 1990)51  
Lack of trust in research Lack of trust in research or the safety of research “Being uncomfortable with research” (Mazzocco 1999)70  
General research concerns Lack of interest in research Lack of interest in research “Not interested in research” (Genetti 2019)47  
Guinea pig concerns Concerns with being the first to experience a new intervention Not wanting “anything tested out” on their child (Chantler 2007)38  
Privacy concerns Concerns regarding privacy of the parent or child “Loss of confidentiality” (Menon 2012)71  
Lack of belief in research General lack of belief in the benefit of research; statements against the general idea of research “Being against research” (Hulst 2005)59  
Discomfort with randomization Discomfort related to randomization and blinding “Parental unwillingness to be blinded to study” (Braga 2014)36  
Genetic testing concerns Concerns regarding genetic testing “Uncomfortable with genetic screening” (Genetti 2019)47  
Informational and consent process related Not enough information provided about study; inadequate understanding of study Not enough information provided about study or inadequate understanding of study by the parent “Lack of information” and “unclear information” (Chappuy 2006)39  
Not enough time to make decision about enrollment Not enough time to make decision about enrollment “Lack of time to make decision” (Eiser 2005)44  
Not enough knowledge about medical condition or lack of comfort with clinical decision Not enough knowledge about medical condition or lack of comfort with clinical decision “Parents did not believe their child had Fragile-X” (Mazzocco 1990)70  
Decision too stressful Decision was too stressful “Overwhelmed with research studies” (Papaz 2012)79  
Parental perception of illness Parental perception of the illness of the child “Patient too ill to participate” (Bartlett 2018)34  
Language Barrier Language barrier “Language barriers” cited as a reason for nonparticipation (Helgesson 2009)54  
Prior experience or lack of experience with research Past experience of lack of experience with medical research, including being enrolled in a different trial at the time “Past experiences with research had both positive and negative effects” (Thomas 2013)93  
Relational Discomfort with proxy nature of consent Discomfort with the parent deciding about participation in a clinical trial for their child Being “uncomfortable making decision on behalf of the child” (Chantler 2007)38  
One parent wanted to enroll, other did not One parent wanted to enroll, the other did not “Discordance in their decision making between parents” (Genetti 2019)47  
Family problems Family problems (eg, divorce) “Family or marital problems” (Mihrshahi 2002)73  
Feeling pressured Feeling pressured to enroll in the trial “Feeling pressured into taking part in the study” (Hayman 2001)53  
Child’s wishes related to enrollment Child’s wishes related to enrollment “Child’s unwillingness to participate” (Greenberg 2017)50  
Decision-making style Decision-making concerns not-otherwise-specified Decision making style: family or self versus shared with doctor (Hoberman 2013)55  
CategoryBarriersDefinitionExample
Concerns about study participation Risk to child Risk to child, including side-effects and safety concerns “Concerns about side-effects” (Buck 2015)37  
Negative impact on medical care Negative impact on medical care, including preference for the standard of care “Study would interfere with the standard care” (Hoberman 2013)55  
Lack of direct benefit to child Lack of a direct benefit to child “Drug was less likely to benefit their child” (D'Amanda 2019)41  
Child's own medical concerns Child's own medical concerns or knowledge “Child does not know true diagnosis” (Chappuy 2006)39  
Phlebotomy concerns Concerns with blood draws “Blood-draw requirements” mentioned as a barrier (D'Amanda 2019)41  
Burdens Logistics or burden of participation Logistics or burdens of participation (eg, travel, time, or money) “Excessive travel” (Bartlett 2018)34  
Lack of trust Lack of trust in clinicians Lack of trust in the clinicians “Poor confidence in physician” (Chappuy 2006)39  
Lack of trust in medical researchers Lack of trust in medical researchers “Distrust of researchers” (Mason 2000)69  
Lack of trust in particular institution Lack of trust in a particular institution (eg, hospital or university) “Distrust in the hospital” (Harth 1990)51  
Lack of trust in medicine in general Lack of trust in medicine in general “Distrust in modern medicine” (Harth 1990)51  
Lack of trust in research Lack of trust in research or the safety of research “Being uncomfortable with research” (Mazzocco 1999)70  
General research concerns Lack of interest in research Lack of interest in research “Not interested in research” (Genetti 2019)47  
Guinea pig concerns Concerns with being the first to experience a new intervention Not wanting “anything tested out” on their child (Chantler 2007)38  
Privacy concerns Concerns regarding privacy of the parent or child “Loss of confidentiality” (Menon 2012)71  
Lack of belief in research General lack of belief in the benefit of research; statements against the general idea of research “Being against research” (Hulst 2005)59  
Discomfort with randomization Discomfort related to randomization and blinding “Parental unwillingness to be blinded to study” (Braga 2014)36  
Genetic testing concerns Concerns regarding genetic testing “Uncomfortable with genetic screening” (Genetti 2019)47  
Informational and consent process related Not enough information provided about study; inadequate understanding of study Not enough information provided about study or inadequate understanding of study by the parent “Lack of information” and “unclear information” (Chappuy 2006)39  
Not enough time to make decision about enrollment Not enough time to make decision about enrollment “Lack of time to make decision” (Eiser 2005)44  
Not enough knowledge about medical condition or lack of comfort with clinical decision Not enough knowledge about medical condition or lack of comfort with clinical decision “Parents did not believe their child had Fragile-X” (Mazzocco 1990)70  
Decision too stressful Decision was too stressful “Overwhelmed with research studies” (Papaz 2012)79  
Parental perception of illness Parental perception of the illness of the child “Patient too ill to participate” (Bartlett 2018)34  
Language Barrier Language barrier “Language barriers” cited as a reason for nonparticipation (Helgesson 2009)54  
Prior experience or lack of experience with research Past experience of lack of experience with medical research, including being enrolled in a different trial at the time “Past experiences with research had both positive and negative effects” (Thomas 2013)93  
Relational Discomfort with proxy nature of consent Discomfort with the parent deciding about participation in a clinical trial for their child Being “uncomfortable making decision on behalf of the child” (Chantler 2007)38  
One parent wanted to enroll, other did not One parent wanted to enroll, the other did not “Discordance in their decision making between parents” (Genetti 2019)47  
Family problems Family problems (eg, divorce) “Family or marital problems” (Mihrshahi 2002)73  
Feeling pressured Feeling pressured to enroll in the trial “Feeling pressured into taking part in the study” (Hayman 2001)53  
Child’s wishes related to enrollment Child’s wishes related to enrollment “Child’s unwillingness to participate” (Greenberg 2017)50  
Decision-making style Decision-making concerns not-otherwise-specified Decision making style: family or self versus shared with doctor (Hoberman 2013)55  

Tables 6 and 7 show the facilitators to pediatric research. In Table 6, we share the number and name of each study that included the facilitator. In Table 7, we present only studies that directly compared the facilitator between enrolled and declined parents. For quantitative comparisons, we present the relevant statistic of the differences by enrollment status.

TABLE 6

Facilitators for Participation in Pediatric Research

CategoryFacilitatorsNumber of StudiesIndividual Studies
Benefits Health benefit to child 39 Barakat 2014,33  Buck 2015,37  Chantler 2007,38  Chappuy 2006,39  Clausen 1954a,40  D'Amanda 2019,a,41  Dahan 2020,22  Dreyzin 2014a,43  Eiser 2005,44  Greenberg 2017,50  Harth 1990,51  Harth 1992,52  Hayman 2001,53  Helgesson 2009,54  Hoberman 2013a,55  Hoehn 2005,56  Ingersgaard 2018,60  Jollye 2009,63  Kumari 2019,66  Langley 1998,68  Mason 2000,69  Morley 2005,74  Mwangi 2017a,75  Nieminen 2015,76  Paquette 2019,80  Read 2009,81  Sammons 2007,82  Shah 2018a,23  Shilling 2009,84  Snowdon 2006,86  Tait 1998,91  Tait 2003a,89  Tait 2004a,90  Thomas 2013,93  Ward 2009,96  Woodgate 2010,97  Woolfall 2013,98  Wynn 2010,99  Zupancic 1997a,24  
Nonhealth benefit to child Chantler 2007,38  D'Amanda 2019,41  Helgesson 2009,54  Shilling 2009,84  Skinner 2011,85  Tait 1998,91  Thomas 2013,93  Wynn 2010.99  
More contact with medical team Chantler 2007,38  Dreyzin 2014,43  Harth 1990,52  Mwangi 2017a.75  
Direct benefit to parent Chantler 2007,38  Harth 1990,51  Helgesson 2009,54  Langley 1998,68  Skinner 2011,85  Ward 2009.96  
Minimal burden to child or parent 16 Buck 2015,37  Dreyzin 2014,43  Eiser 2005,44  Greenberg 2017,50  Helgesson 2009,54  Hoberman 2013a,55  Mason 2000,69  Pagano-Therrien 2017,78  Paquette 2019,80  Read 2009,81  Sammons 2007,82  Shilling 2009,84  Skinner 2011,85  Taylor 2015a,92  Tait 1998,91  Woodgate 2010.97  
Financial reimbursement Bartlett 2018,34  Harth 1990,51  Skinner 2011,85  Taylor 2015a,92  
Trust Trust in clinician 13 Chantler 2007,38  Chappuy 2006,39  Dahan 2020,22  Dreyzin 2014,43  Eiser 2005,44  Greenberg 2017,50  Ingersgaard 2018,60  Jollye 2009,63  Mwangi 2017,75  Nieminen 2015a,76  Pagano-Therrien 2017,78  Snowdon 2006,86  Woodgate 2010.97  
Trust in medical researchers Helgesson 2009,54  Jenkins 2009,62  Shah 2018a,23  Snowdon 2006.86  
Trust in particular institution Harth 1990,51  Jenkins 2009,62  Vecchi 2013.94  
Trust in medicine in general Clausen 1954,40  Tait 2004.90  
Trust in research Chantler 2007,38  Clausen 1954,40  Hoberman 2013a,55  Paquette 2019.80  
Trust (other) Chantler 2007a,38  Jenkins 2009,62  Tait 2003a.89  
Support of research Altruism 30 Barakat 2014,33  Chantler 2007,38  D'Amanda 2019,41  Dahan 2020,22  Eiser 2005,44  Harth 1990,51  Harth 1992,52  Hoberman 2013a,55  Hoehn 2005,56  Ingersgaard 2018,60  Jenkins 2009,62  Jollye 2009,63  Langley 1998,68  Mason 2000,69  Morley 2005,74  Nieminen 2015a,76  Pagano-Therrien 2017,78  Paquette 2019,80  Read 2009,81  Sammons 2007,82  Shah 2018a,23  Shilling 2009,84  Tait 1998,91  Tait 2003a,89  Thomas 2013,93  Vecchi 2013,94  Ward 2009,96  Woodgate 2010,97  Woolfall 2013,98  Zupancic 1997a.24  
Importance of medical research 26 Bartlett 2018,34  Buck 2015,37  Chantler 2007,38  Clausen 1954,40  Dahan 2020,22  Dreyzin 2014,43  Harth 1990,51  Harth 1992,52  Hayman 2001,53  Helgesson 2009,54  Hoberman 2013a,55  Jenkins 2009,62  Jollye 2009,63  Kumari 2019,66  Langley 1998,68  Pagano-Therrien 2017,78  Sammons 2007,82  Shah 2018a,23  Shilling 2009,84  Skinner 2011,85  Snowdon 2006,86  Tait 1998,91  Tait 2003a,89  Thomas 2013,89  Vecchi 2013,94  Wynn 2010.99  
Informational and consent process related Felt as only option Chappuy 2006,39  Dahan 2020,22  Hayman 2001,53  Snowdon 2006,86  Ward 2009,96  Woodgate 2010,97  Zupancic 1997.24  
Understanding of research materials Tait 1998,91  Tait 2003a.89  
Experience or lack of experience with research Baxter 2012a,35  Chantler 2007,38  Chappuy 2006a,39  Jay 2007a,61  Pagano-Therrien 2017,78  Read 2009a,81  Tait 2003a,89  Zupancic 1997a.24  
Relational Positive relationship to researcher 15 Bartlett 2018,34  Dahan 2020,22  Harth 1990,51  Hoberman 2013a,55  Jay 2007a,61  Pagano-Therrien 2017,78  Snowdon 2006,86  Sureshkumar 2012a,87  Tait 1998,91  Tait 2003a,89  Tait 2004,90  Thomas 2013,93  Ward 2009,96  Woodgate 2010,97  Woolfall 2013.98  
Influence of family and friends 11 Bartlett 2018,34  Baxter 2012,35  Clausen 1954a,40  Harth 1990,51  Helgesson 2009,54  Hoberman 2013a,55  Jollye 2009,63  Read 2009,81  Skinner 2011,85  Tait 2003a,89  Woodgate 2010.97  
Participation encouraged by clinical team 11 Clausen 1954a,40  Harth 1990,51  Langley 1998,68  Mazzocco 1999a,70  Paquette 2019,80  Read 2009,81  Sammons 2007,82  Snowdon 2006,86  Woodgate 2010,97  Woolfall 2013,98  Zupancic 1997a.24  
Child’s desire to participate Pagano-Therrien 2017,78  Paquette 2019.80  
CategoryFacilitatorsNumber of StudiesIndividual Studies
Benefits Health benefit to child 39 Barakat 2014,33  Buck 2015,37  Chantler 2007,38  Chappuy 2006,39  Clausen 1954a,40  D'Amanda 2019,a,41  Dahan 2020,22  Dreyzin 2014a,43  Eiser 2005,44  Greenberg 2017,50  Harth 1990,51  Harth 1992,52  Hayman 2001,53  Helgesson 2009,54  Hoberman 2013a,55  Hoehn 2005,56  Ingersgaard 2018,60  Jollye 2009,63  Kumari 2019,66  Langley 1998,68  Mason 2000,69  Morley 2005,74  Mwangi 2017a,75  Nieminen 2015,76  Paquette 2019,80  Read 2009,81  Sammons 2007,82  Shah 2018a,23  Shilling 2009,84  Snowdon 2006,86  Tait 1998,91  Tait 2003a,89  Tait 2004a,90  Thomas 2013,93  Ward 2009,96  Woodgate 2010,97  Woolfall 2013,98  Wynn 2010,99  Zupancic 1997a,24  
Nonhealth benefit to child Chantler 2007,38  D'Amanda 2019,41  Helgesson 2009,54  Shilling 2009,84  Skinner 2011,85  Tait 1998,91  Thomas 2013,93  Wynn 2010.99  
More contact with medical team Chantler 2007,38  Dreyzin 2014,43  Harth 1990,52  Mwangi 2017a.75  
Direct benefit to parent Chantler 2007,38  Harth 1990,51  Helgesson 2009,54  Langley 1998,68  Skinner 2011,85  Ward 2009.96  
Minimal burden to child or parent 16 Buck 2015,37  Dreyzin 2014,43  Eiser 2005,44  Greenberg 2017,50  Helgesson 2009,54  Hoberman 2013a,55  Mason 2000,69  Pagano-Therrien 2017,78  Paquette 2019,80  Read 2009,81  Sammons 2007,82  Shilling 2009,84  Skinner 2011,85  Taylor 2015a,92  Tait 1998,91  Woodgate 2010.97  
Financial reimbursement Bartlett 2018,34  Harth 1990,51  Skinner 2011,85  Taylor 2015a,92  
Trust Trust in clinician 13 Chantler 2007,38  Chappuy 2006,39  Dahan 2020,22  Dreyzin 2014,43  Eiser 2005,44  Greenberg 2017,50  Ingersgaard 2018,60  Jollye 2009,63  Mwangi 2017,75  Nieminen 2015a,76  Pagano-Therrien 2017,78  Snowdon 2006,86  Woodgate 2010.97  
Trust in medical researchers Helgesson 2009,54  Jenkins 2009,62  Shah 2018a,23  Snowdon 2006.86  
Trust in particular institution Harth 1990,51  Jenkins 2009,62  Vecchi 2013.94  
Trust in medicine in general Clausen 1954,40  Tait 2004.90  
Trust in research Chantler 2007,38  Clausen 1954,40  Hoberman 2013a,55  Paquette 2019.80  
Trust (other) Chantler 2007a,38  Jenkins 2009,62  Tait 2003a.89  
Support of research Altruism 30 Barakat 2014,33  Chantler 2007,38  D'Amanda 2019,41  Dahan 2020,22  Eiser 2005,44  Harth 1990,51  Harth 1992,52  Hoberman 2013a,55  Hoehn 2005,56  Ingersgaard 2018,60  Jenkins 2009,62  Jollye 2009,63  Langley 1998,68  Mason 2000,69  Morley 2005,74  Nieminen 2015a,76  Pagano-Therrien 2017,78  Paquette 2019,80  Read 2009,81  Sammons 2007,82  Shah 2018a,23  Shilling 2009,84  Tait 1998,91  Tait 2003a,89  Thomas 2013,93  Vecchi 2013,94  Ward 2009,96  Woodgate 2010,97  Woolfall 2013,98  Zupancic 1997a.24  
Importance of medical research 26 Bartlett 2018,34  Buck 2015,37  Chantler 2007,38  Clausen 1954,40  Dahan 2020,22  Dreyzin 2014,43  Harth 1990,51  Harth 1992,52  Hayman 2001,53  Helgesson 2009,54  Hoberman 2013a,55  Jenkins 2009,62  Jollye 2009,63  Kumari 2019,66  Langley 1998,68  Pagano-Therrien 2017,78  Sammons 2007,82  Shah 2018a,23  Shilling 2009,84  Skinner 2011,85  Snowdon 2006,86  Tait 1998,91  Tait 2003a,89  Thomas 2013,89  Vecchi 2013,94  Wynn 2010.99  
Informational and consent process related Felt as only option Chappuy 2006,39  Dahan 2020,22  Hayman 2001,53  Snowdon 2006,86  Ward 2009,96  Woodgate 2010,97  Zupancic 1997.24  
Understanding of research materials Tait 1998,91  Tait 2003a.89  
Experience or lack of experience with research Baxter 2012a,35  Chantler 2007,38  Chappuy 2006a,39  Jay 2007a,61  Pagano-Therrien 2017,78  Read 2009a,81  Tait 2003a,89  Zupancic 1997a.24  
Relational Positive relationship to researcher 15 Bartlett 2018,34  Dahan 2020,22  Harth 1990,51  Hoberman 2013a,55  Jay 2007a,61  Pagano-Therrien 2017,78  Snowdon 2006,86  Sureshkumar 2012a,87  Tait 1998,91  Tait 2003a,89  Tait 2004,90  Thomas 2013,93  Ward 2009,96  Woodgate 2010,97  Woolfall 2013.98  
Influence of family and friends 11 Bartlett 2018,34  Baxter 2012,35  Clausen 1954a,40  Harth 1990,51  Helgesson 2009,54  Hoberman 2013a,55  Jollye 2009,63  Read 2009,81  Skinner 2011,85  Tait 2003a,89  Woodgate 2010.97  
Participation encouraged by clinical team 11 Clausen 1954a,40  Harth 1990,51  Langley 1998,68  Mazzocco 1999a,70  Paquette 2019,80  Read 2009,81  Sammons 2007,82  Snowdon 2006,86  Woodgate 2010,97  Woolfall 2013,98  Zupancic 1997a.24  
Child’s desire to participate Pagano-Therrien 2017,78  Paquette 2019.80  
a

Study directly compared by enrollment status. See Table 7 for more detail.

TABLE 7

Comparison of Facilitators for Participation in Pediatric Research between Participants and Nonparticipants

CategoryFacilitators Directly ComparedStudyDiscussionStatistics
Benefits Health benefit to child Clausen 1954b,40  More consenting mothers (66%) than decliners (7%) reported believing that the vaccine had the potential to prevent polio NA 
D’Amanda 2019b,41  More joiners (8/16) than decliners (2/15) believed medication usage would have a positive effect on health NA 
Dreyzin 2014b,43  More consenters (5/5) than decliners (0/1) reported being motivated by “an acute deterioration in their child’s health” NA 
Hoberman 2013a,55  Consenters had higher “benefit to my child” scores than nonconsenters P < .001 
a Consenters were more likely than nonconsenters to endorse that the “study may enhance standard of care” P < .001 
Mwangi 2017b,75  More participants (13/20) than decliners (1/15) discussed “potential therapeutic benefit to child of participating” NA 
bMore participants (18/20) than decliners (3/15) “demonstrated belief that participants got malaria treatment” NA 
Shah 2018a,23  Enrollers (101/105) were more likely than decliners (41/58) to rate “the potential benefit to my child” as “very important or important” to their decision making P < .001 
Tait 2003a,89  Consenters had higher scores on “perceived study as benefit to child” compared with nonconsenters P < .001 
Tait 2004a,90  Consenters were more likely than decliners to view the risk-benefit ratio as lower P < .001 
More contact with medical team Zupancic 1997a,24  Consenters assessed study as of greater benefit and lower risk compared with nonconsenters P < .0001 
Mwangi 2017c,75  Participants (12/20) and decliners (11/15) “discussed a general perception of benefit in access to ancillary clinical services for participants” NA 
cParticipants (6/20) and decliners (7/15) “demonstrated belief that there was a significant benefit in access to ancillary clinical services for participants” NA 
Minimal burden to child Hoberman 2013a,55  Consenters were more likely than nonconsenters to perceive the study as low risk P < .001 
Taylor 2015e,92  Patients in non-brief studies were more likely to participate than those in brief studies OR 1.7, P < .001 
a Patients in noninvasive studies were more likely to participant than those in invasive studies OR 2.9, P < .001 
Financial reimbursement Taylor 2015e,92  Patients in studies with no compensation were more likely to participate than those with compensation OR 1.9, P < .001 
Trust Trust in clinician Nieminen 2015a,76  Consenters (771/956) were more likely than nonconsenters (n = 242/356) to agree or strongly agree with the statement: “I trust my own well-baby-clinic nurse in matters related to my child's health” P < .001 
Trust in medical researchers Shah 2018a,23  Enrollers (87%) were more likely than decliners (63%) to report trusting the person who discussed the PENUT trial with them P < .001 
Trust in research Hoberman 2013a,55  Consenters had higher “trust in research” scores than nonconsenters P < .001 
Chantler 2007b,38  More parents who enrolled than parents who declined enrollment reported a general trust in vaccines NA 
Trust (other) Tait 2003a,89  Consenters had higher “trust” scores (12.1 on scale of 3–15) than nonconsenters (11.1) P < .001 
Support of research Altruism Hoberman 2013a,55  Consenters had higher altruism scores than nonconsenters P < .001 
Nieminen 2015b,76  More consenters (742/965) than nonconsenters (241/356) reported that “promoting the common good” had an impact on their enrollment decision NA 
Shah 2018a,23  Enrollers (96/105) were more likely than decliners (37/58) to rate “the potential benefit to future premature babies” as “very important or important” P < .001 
Tait 2003a,89  Consenters had higher perception of the “benefit to others” (7.8 on a scale of 1–10) than nonconsenters (5.9) P < .001 
c Consenters had no difference in altruism construct score (12.9 on scale of 1–15) than nonconsenters (12.7) P = NS 
Zupancic 1997b,24  More consenters (98%) than decliners (84%) considered “altruistic motives” as important in their decision NA 
Importance of medical research Hoberman 2013a,55  Consenters had higher “importance of research study” scores than nonconsenters P < .001 
Shah 2018a,23  Enrollers (86/105) were more likely than decliners (23/58) to rate “the contribution to science and medicine” as “very important or important” P < .001 
Tait 2003a89  Consenters viewed the study as more important (8.0 on scale of 1–10) than nonconsenters (5.9) P < .001 
Informational and consent process related Understanding of research materials Tait 2003a89  Consenters were more likely to have listened completely (89.3%) than nonconsenters (67.8%) P < .0001 
a Consenters were more likely to have read the consent completely (62.0%) than nonconsenters (43.0%) P < .0001 
a Consenters were more likely to have completely understood the consent (77.5%) than nonconsenters (58.4%) P < .0001 
Experience or lack of experience with research Baxter 2012c,89  Parents were not more likely to enroll their child if they had another child participating in the same study P = NS 
Chappuy 2006c,39  Those who enrolled and those who declined did not differ in prior experience with research P = NS 
Jay 2007a,61  Consenters to a follow up study were more likely than non-consenters to report a positive recollection of their child's care at past study visits P = .001 
Read 2009a,81  Parents who had participated in research themselves were more likely to authorize their child to participate in a research trial P < .001 
Tait 2003c,89  Consenters did not differ in prior research experience of the child (20.0%) compared with nonconsenters (18.3%) P = NS 
c Consenters did not differ in prior research experience of the parent (24.4%) compared with nonconsenters (21.5%) P = NS 
Zupancic 1997c,24  Consenters (17%) and nonconsenters (22%) reported similar rates of previous research involvement NA 
Relational Positive relationship to researcher Hoberman 2013a,55  Consenters had higher scores for “perceived friendliness and professionalism of researcher” than nonconsenters P < .003 
Jay 2007a,61  “Study staff contactable at any time to answer query” influenced parents to consent P = .01 
Sureshkumar 2012a,87  Referral to the study by a pediatrician or nephrologist increased likelihood of consent compared with referral from emergency department P < .0001 
 Recruiting physician being part of the research team increased likelihood of consent RR 1.9, P < .001, 
Tait 2003a,89  Consenters were more likely (97%) than nonconsenters (87%) to view researcher as “friendly and relaxed” P < .0001 
Influence of family and friends Clausen 1954b,40  More consenters (61%) than decliners (39%) discussed with family and friends NA 
Hoberman 2013c,55  Consenters did not differ from nonconsenters in responses to question set on “external influences” P = NS 
Tait 2003c,89  Consenters (52.0%) and nonconsenters (55.9%) did not differ in “discussed the study information with others before decision” P = NS 
c Consenters (40.3%) and nonconsenters (46.3%) did not differ in “discussed with spouse” P = NS 
Participation encouraged by clinical team Clausen 1954b,40  More consenters (41%) than decliners (27%) discussed study with doctor or nurse before making decision about vaccine NA 
Mazzocco 1999a,70  Enrollment was higher when the research was introduced by a physician (73.3%) than by research staff (58.7%) P < .01 
Zupancic 1997c,24  Some consenters (34/103) and nonconsenters (11/37) both endorsed that they “prefer to have the doctor advise me whether the baby should be in the study, rather than asking me to decide” NA 
CategoryFacilitators Directly ComparedStudyDiscussionStatistics
Benefits Health benefit to child Clausen 1954b,40  More consenting mothers (66%) than decliners (7%) reported believing that the vaccine had the potential to prevent polio NA 
D’Amanda 2019b,41  More joiners (8/16) than decliners (2/15) believed medication usage would have a positive effect on health NA 
Dreyzin 2014b,43  More consenters (5/5) than decliners (0/1) reported being motivated by “an acute deterioration in their child’s health” NA 
Hoberman 2013a,55  Consenters had higher “benefit to my child” scores than nonconsenters P < .001 
a Consenters were more likely than nonconsenters to endorse that the “study may enhance standard of care” P < .001 
Mwangi 2017b,75  More participants (13/20) than decliners (1/15) discussed “potential therapeutic benefit to child of participating” NA 
bMore participants (18/20) than decliners (3/15) “demonstrated belief that participants got malaria treatment” NA 
Shah 2018a,23  Enrollers (101/105) were more likely than decliners (41/58) to rate “the potential benefit to my child” as “very important or important” to their decision making P < .001 
Tait 2003a,89  Consenters had higher scores on “perceived study as benefit to child” compared with nonconsenters P < .001 
Tait 2004a,90  Consenters were more likely than decliners to view the risk-benefit ratio as lower P < .001 
More contact with medical team Zupancic 1997a,24  Consenters assessed study as of greater benefit and lower risk compared with nonconsenters P < .0001 
Mwangi 2017c,75  Participants (12/20) and decliners (11/15) “discussed a general perception of benefit in access to ancillary clinical services for participants” NA 
cParticipants (6/20) and decliners (7/15) “demonstrated belief that there was a significant benefit in access to ancillary clinical services for participants” NA 
Minimal burden to child Hoberman 2013a,55  Consenters were more likely than nonconsenters to perceive the study as low risk P < .001 
Taylor 2015e,92  Patients in non-brief studies were more likely to participate than those in brief studies OR 1.7, P < .001 
a Patients in noninvasive studies were more likely to participant than those in invasive studies OR 2.9, P < .001 
Financial reimbursement Taylor 2015e,92  Patients in studies with no compensation were more likely to participate than those with compensation OR 1.9, P < .001 
Trust Trust in clinician Nieminen 2015a,76  Consenters (771/956) were more likely than nonconsenters (n = 242/356) to agree or strongly agree with the statement: “I trust my own well-baby-clinic nurse in matters related to my child's health” P < .001 
Trust in medical researchers Shah 2018a,23  Enrollers (87%) were more likely than decliners (63%) to report trusting the person who discussed the PENUT trial with them P < .001 
Trust in research Hoberman 2013a,55  Consenters had higher “trust in research” scores than nonconsenters P < .001 
Chantler 2007b,38  More parents who enrolled than parents who declined enrollment reported a general trust in vaccines NA 
Trust (other) Tait 2003a,89  Consenters had higher “trust” scores (12.1 on scale of 3–15) than nonconsenters (11.1) P < .001 
Support of research Altruism Hoberman 2013a,55  Consenters had higher altruism scores than nonconsenters P < .001 
Nieminen 2015b,76  More consenters (742/965) than nonconsenters (241/356) reported that “promoting the common good” had an impact on their enrollment decision NA 
Shah 2018a,23  Enrollers (96/105) were more likely than decliners (37/58) to rate “the potential benefit to future premature babies” as “very important or important” P < .001 
Tait 2003a,89  Consenters had higher perception of the “benefit to others” (7.8 on a scale of 1–10) than nonconsenters (5.9) P < .001 
c Consenters had no difference in altruism construct score (12.9 on scale of 1–15) than nonconsenters (12.7) P = NS 
Zupancic 1997b,24  More consenters (98%) than decliners (84%) considered “altruistic motives” as important in their decision NA 
Importance of medical research Hoberman 2013a,55  Consenters had higher “importance of research study” scores than nonconsenters P < .001 
Shah 2018a,23  Enrollers (86/105) were more likely than decliners (23/58) to rate “the contribution to science and medicine” as “very important or important” P < .001 
Tait 2003a89  Consenters viewed the study as more important (8.0 on scale of 1–10) than nonconsenters (5.9) P < .001 
Informational and consent process related Understanding of research materials Tait 2003a89  Consenters were more likely to have listened completely (89.3%) than nonconsenters (67.8%) P < .0001 
a Consenters were more likely to have read the consent completely (62.0%) than nonconsenters (43.0%) P < .0001 
a Consenters were more likely to have completely understood the consent (77.5%) than nonconsenters (58.4%) P < .0001 
Experience or lack of experience with research Baxter 2012c,89  Parents were not more likely to enroll their child if they had another child participating in the same study P = NS 
Chappuy 2006c,39  Those who enrolled and those who declined did not differ in prior experience with research P = NS 
Jay 2007a,61  Consenters to a follow up study were more likely than non-consenters to report a positive recollection of their child's care at past study visits P = .001 
Read 2009a,81  Parents who had participated in research themselves were more likely to authorize their child to participate in a research trial P < .001 
Tait 2003c,89  Consenters did not differ in prior research experience of the child (20.0%) compared with nonconsenters (18.3%) P = NS 
c Consenters did not differ in prior research experience of the parent (24.4%) compared with nonconsenters (21.5%) P = NS 
Zupancic 1997c,24  Consenters (17%) and nonconsenters (22%) reported similar rates of previous research involvement NA 
Relational Positive relationship to researcher Hoberman 2013a,55  Consenters had higher scores for “perceived friendliness and professionalism of researcher” than nonconsenters P < .003 
Jay 2007a,61  “Study staff contactable at any time to answer query” influenced parents to consent P = .01 
Sureshkumar 2012a,87  Referral to the study by a pediatrician or nephrologist increased likelihood of consent compared with referral from emergency department P < .0001 
 Recruiting physician being part of the research team increased likelihood of consent RR 1.9, P < .001, 
Tait 2003a,89  Consenters were more likely (97%) than nonconsenters (87%) to view researcher as “friendly and relaxed” P < .0001 
Influence of family and friends Clausen 1954b,40  More consenters (61%) than decliners (39%) discussed with family and friends NA 
Hoberman 2013c,55  Consenters did not differ from nonconsenters in responses to question set on “external influences” P = NS 
Tait 2003c,89  Consenters (52.0%) and nonconsenters (55.9%) did not differ in “discussed the study information with others before decision” P = NS 
c Consenters (40.3%) and nonconsenters (46.3%) did not differ in “discussed with spouse” P = NS 
Participation encouraged by clinical team Clausen 1954b,40  More consenters (41%) than decliners (27%) discussed study with doctor or nurse before making decision about vaccine NA 
Mazzocco 1999a,70  Enrollment was higher when the research was introduced by a physician (73.3%) than by research staff (58.7%) P < .01 
Zupancic 1997c,24  Some consenters (34/103) and nonconsenters (11/37) both endorsed that they “prefer to have the doctor advise me whether the baby should be in the study, rather than asking me to decide” NA 

NS, not significant; OR, odds ratio; RR, risk ratio.

a

Significantly associated with enrolling (quantitative only: P < .05).

b

Tends toward enrolling (quantitative: [P ≥ .05 and P ≤ .1] or qualitative).

c

No difference (quantitative or qualitative).

d

Tends toward declining (quantitative: [P ≥ .05 and P ≤ .1] or qualitative).

e

Significantly associated with declining (quantitative only: P < .05).

Benefits

The perceived benefits of pediatric research participation were strong facilitators for research participation. The most frequently reported facilitator was health benefit to child (N = 39) with nearly all studies that compared by enrollment status reporting that the perception of health benefit to child was associated with enrollment. A belief that participation was a minimal burden to child or parent (N = 16) was also associated with enrollment. Four studies identified financial reimbursement as a facilitator to research participation. The single manuscript that compared by enrollment status looked at research participation in a pediatric emergency department and found that studies without compensation had higher enrollment for moderate to very invasive studies.92  Because invasive studies were more likely to have compensation, the authors were unable to compare similar studies with and without compensation to fully understand the effects of compensation.

Trust

Trust emerged as an important theme in pediatric research participation. Studies frequently reported trust as a facilitator to pediatric research participation including trust in clinicians (N = 13), medical researchers (N = 4), medical institutions (N = 3), medicine (N = 2), medical research (N = 4), as well as undefined trust (N = 1), trust in vaccines (N = 1) and trust in government (N = 1). For each trust category, all studies that compared by enrollment status (N = 5) found greater trust to be associated with enrollment.

Support of Research

Another major theme was parental support of research. Within this category, we included altruism, importance of medical research, and prior experience with research. Studies found altruism (N = 30) to be the second most frequently reported facilitator surpassed only by health benefit to child (N = 39). Studies also reported the importance of research (N = 26) as a facilitator to research participation. For each of these 3 categories, all studies that compared parents by enrollment status found an association between the facilitator and enrollment.

Informational and Consent Process Related

Facilitators emerged related to the consent process and information sharing. These included research participation being “felt as the only option,” understanding of research materials, and prior experience with research. All studies that compared by enrollment status found greater understanding among those who enrolled. Prior research experience was variably associated with enrollment status.

Relational

Several facilitators to participation emerged related to parental relationships. These included positive relationship to researcher, influence of families and friends, clinical team encouragement of participation, and a child’s desire to participate. The most frequently reported facilitators in this category were a positive relationship with researcher (N = 15), influence of family and friends (N = 11), and clinical team encouragement of participation (N = 11). For clinical team encouragement, all studies that compared by enrollment status found an association between this facilitator and enrollment.

Changes Over Time

Facilitators to research were examined across decades to assess for changes over time. Nearly all included studies (N = 67 of 70) were published in the 1990s (N = 6), 2000s (N = 22), or 2010s (N = 39). The most cited facilitators to enrollment in each of these 3 epochs (1990s, 2000s, 2010s) were health benefit to child (N = 5, N = 15, N = 17), altruism (N = 5, N = 11, N = 13), and importance of research (N = 4, N = 8, N = 12). No trends suggesting changes over time were evident.

Tables 8 and 9 show the barriers to pediatric research. In Table 8, we share the number and name of each study that included the barrier. In Table 9, we present only studies that directly compared the barrier between enrolled and declined parents. For quantitative comparisons, we present the relevant statistic of the differences by enrollment status.

TABLE 8

Barriers for Participation in Pediatric Research

CategoryBarriersNumber of StudiesIndividual Studies
Concerns about study participation Risk to child 46 Bartlett 2018,34  Braga 2014,36  Buck 2015,37  Chantler 2007,38  Chappuy 2006,39  Clausen 1954a,40  D'Amanda 2019a,41  Dreyzin 2014,43  Eiser 2005,44  Elemraid 2013,45  Gill 2014,48  Greenberg 2017,50  Harth 1990,51  Hayman 2001a,53  Helgesson 2009,54  Hoberman 2013a,55  Hoehn 2005,56  Howard Sharp 2020,58  Hulst 2005,59  Ingersgaard 2018,60  Jollye 2009,63  Korotchikova 2010,65  Kumari 2019,66  Langley 1998,68  Mason 2000,69  Menon 2012,71  Menon 2014,72  Mwangi 2017a,75  Nieminen 2015,76  Norris 2010,77  Papaz 2012,79  Paquette 2019,80  Read 2009,81  Shah 2018a,23  Shilling 2009,84  Snowdon 2006,86  Surun 2018,88  Tait 1998,91  Tait 2003a,89  Tait 2004a,90  Thomas 2013,93  Volkening 2017,95  Ward 2009,96  Woodgate 2010,97  Woolfall 2013,98  Zupancic 1997a.24  
Negative impact on medical care 21 Barakat 2014,33  Baxter 2012,35  Braga 2014,36  Buck 2015,37  Clausen 1954,40  D'Amanda 2019,41  Elemraid 2013,45  Gattuso 2006,46  Genetti 2019,47  Gonzalez 2016,49  Helgesson 2009,54  Hoberman 2013a,55  Ingersgaard 2018,60  Menon 2014,72  Mihrshahi 2002,73  Morley 2005,74  Sureshkumar 2012,87  Tait 1998,91  Tait 2003a,89  Taylor 2015,92  Woolfall 2013.98  
Lack of direct benefit to child 16 Barakat 2014,33  Bartlett 2018,34  Clausen 1954,40  D'Amanda 2019a,41  Gattuso 2006,46  Genetti 2011,47  Gill 2014,48  Greenberg 2017,50  Helgesson 2009,54  Howard Sharp 2020,58  Kick 2018,64  Menon 2014,72  Mihrshahi 2002,73  Read 2009,81  Skinner 2011,85  Sureshkumar 2012.87  
Child's own medical concerns Chappuy 2006,39  Hulst 2005,59  Menon 2014,72  Mihrshahi 2002,73  Morley 2005,74  Sureshkumar 2012,87  Taylor 2015,92  Thomas 2013,93  Woodgate 2010.97  
Phlebotomy concerns 14 Chantler 2007,38  D'Amanda 2019a,41  Dlugos 2005,42  Helgesson 2009,54  Jay 2007a,61  Jenkins 2009,62  Kick 2018,64  Labib 2018,67  Mazzocco 1999,70  Menon 2012,71  Menon 2014,72  Scollon 2014,83  Vecchi 2013,94  Wynn 2010.99  
Burdens Logistics or burden of participation 35 Bartlett 2018,34  Baxter 2012,35  Chappuy 2006,39  D'Amanda 2019a,41  Gattuso 2006,46  Genetti 2019,47  Gill 2014,48  Gonzalez 2016,49  Greenberg 2017,50  Harth 1990,51  Hayman 2001,53  Helgesson 2009,54  Hoehn 2009,56  Hulst 2005,59  Jenkins 2009,62  Kick 2018,64  Korotchikova 2010,65  Langley 1998,68  Mason 2000,69  Mazzocco 1999,70  Mihrshahi 2002,73  Papaz 2012,79  Paquette 2019,80  Read 2009,81  Shilling 2009,84  Skinner 2011,85  Sureshkumar 2012,87  Tait 1998,91  Tait 2003a,89  Taylor 2015,92  Vecchi 2013,94  Volkening 2017,95  Woolfall 2013,98  Wynn 2010,99  Zupancic 1997a.24  
Lack of trust Lack of trust in clinicians Chappuy 2006.39  
Lack of trust in medical researchers Greenberg 2017,50  Helgesson 2009,54  Mason 2000,69  Read 2009,81  Shah 2018a,23  Wynn 2010.99  
Lack of trust in particular institution Harth 1990,51  Morley 2005.74  
Lack of trust in medicine in general Buck 2015,37  Harth 1990.51  
Lack of trust in research Chantler 2007,38  Dreyzin 2014,43  Mazzocco 1999,70  Snowdon 2006.86  
General research concerns Lack of interest in research 18 Braga 2014,36  Elemraid 2013,45  Gattuso 2006,46  Genetti 2019,47  Gonzalez 2016,49  Harth 1990,51  Hulst 2005,59  Langley 1998,68  Mazzocco 1999,70  Menon 2012,71  Menon 2014,72  Mihrshahi 2002,73  Morley 2005,74  Papaz 2012,79  Sammons 2007,82  Skinner 2011,85  Taylor 2015,92  Volkening 2017.95  
Guinea pig concerns Buck 2015,37  Chantler 2007,38  Clausen 1954,40  Greenberg 2017,50  Hoehn 2005,56  Korotchikova 2010,65  Shah 2018a,23  Tait 1998.91  
Privacy concerns 12 Gattuso 2006,46  Genetti 2019,47  Gill 2014,48  Harth 1990,51  Howard Sharp 2020,58  Kick 2018,64  Kumari 2019,66  Menon 2012,71  Papaz 2012,79  Sammons 2007,82  Scollon 2014,83  Tait 2004.90  
Lack of belief in research Helgesson 2009,44  Hulst 2005,59  Labib 2018,67  Nieminen 2015,76  Taylor 2015,92  Tait 1998a.91  
Discomfort with randomization 18 Braga 2014,54  Buck 2015,37  Eiser 2005,76  Gonzalez 2016,49  Greenberg 2017,50  Hoberman 2013a,55  Ingersgaard 2018,60  Jollye 2009,63  Kick 2018,64  Nieminen 2015,76  Norris 2010,77  Sammons 2007,82  Snowdon 2006,86  Surun 2018,88  Tait 1998,91  Woodgate 2010,97  Woolfall 2013,98  Wynn 2010.99  
Genetic testing concerns Genetti 2019,47  Howard Sharp 2020,58  Papaz 2012,79  Scollon 2014,83  Skinner 2011.85  
Informational and consent process related Not enough information provided about study; inadequate understanding of study 16 Barakat 2014,33  Chappuy 2006,39  Dahan 2020,22  Dreyzin 2014,43  Eiser 2005,44  Gill 2014,48  Helgesson 2009,54  Hoberman 2013a,55  Korotchikova 2010,65  Menon 2012,71  Menon 2014,72  Mwangi 2017a,75  Paquette 2019,80  Read 2009,81  Tait 2003a,89  Tait 2004.90  
Not enough time to make decision about enrollment 13 Barakat 2014,33  Chappuy 2006,39  Eiser 2005,44  Hoehn 2009a,56  Jollye 2009,63  Menon 2012,71  Papaz 2012,79  Paquette 2019,80  Snowdon 2006,86  Tait 1998,91  Tait 2004,90  Thomas 2013,93  Ward 2009.96  
Not enough knowledge about medical condition or lack of comfort with clinical decision Mazzocco 1999,70  Read 2009a.81  
Decision too stressful 29 Dahan 2020,22  Dlugos 2005,42  Genetti 2019,47  Greenberg 2017,50  Hoberman 2013a,55  Howard Sharp 2020,58  Hulst 2005,59  Ingersgaard 2018,60  Jollye 2009,63  Labib 2018,67  Mason 2000,69  Menon 2012,71  Menon 2014,72  Norris 2010,77  Papaz 2012,79  Paquette 2019,80  Read 2009,81  Sammons 2007,82  Scollon 2014,83  Shah 2018a,23  Snowdon 2006,86  Tait 1998a,91  Tait 2003a,90  Tait 2004,89  Thomas 2013,93  Ward 2009,96  Woodgate 2010,97  Woolfall 2013,98  Zupancic 1997a.24  
Parental perception of illness 10 Barakat 2014,33  Bartlett 2018,34  Buck 2015,37  Chantler 2007a,38  Clausen 1954,40  D'Amanda 2019a,41  Dreyzin 2014a,43  Jollye 2009,63  Wynn 2010,99  Zupancic 1997a.24  
Language barrier Helgesson 2009,54  Papaz 2012.79  
Prior experience or lack of experience with research 13 Chantler 2007a,38  Dahan 2020,22  Gonzalez 2016,49  Hulst 2005,59  Menon 2012,71  Menon 2014,72  Nieminen 2015a,76  Paquette 2019a,80  Shah 2018a,23  Tait 1998a,91  Tait 2003a,90  Tait 2004,89  Thomas 2013a.93  
Relational Discomfort with proxy nature of consent Chantler 2007,38  Papaz 2012,79  Woodgate 2010.97  
One parent wanted to enroll, other did not Dahan 2020,22  Genetti 2019,47  Hoehn 2009,56  Jenkins 2009,62  Korotchikova 2010a,65  Langley 1998,68  Menon 2014,72  Skinner 2011.85  
Family problems Baxter 2012,35  Chantler 2007,38  Jay 2007a,61  Menon 2012,71  Mihrshahi 2002.73  
Feeling pressured Hayman 2001a,53  Mason 2000.69  
Child's wishes related to enrollment 15 Chantler 2007,38  Chappuy 2006,39  Clausen 1954,40  Gill 2014,48  Greenberg 2017,50  Howard Sharp 2020,58  Hulst 2005,59  Ingersgaard 2018,60  Jay 2007a,61  Menon 2014,72  Shilling 2009,84  Sureshkumar 2012,87  Tait 2003a,90  Woodgate 2010,97  Woolfall 2013.98  
Decision-making style Hoberman 2013a55  
CategoryBarriersNumber of StudiesIndividual Studies
Concerns about study participation Risk to child 46 Bartlett 2018,34  Braga 2014,36  Buck 2015,37  Chantler 2007,38  Chappuy 2006,39  Clausen 1954a,40  D'Amanda 2019a,41  Dreyzin 2014,43  Eiser 2005,44  Elemraid 2013,45  Gill 2014,48  Greenberg 2017,50  Harth 1990,51  Hayman 2001a,53  Helgesson 2009,54  Hoberman 2013a,55  Hoehn 2005,56  Howard Sharp 2020,58  Hulst 2005,59  Ingersgaard 2018,60  Jollye 2009,63  Korotchikova 2010,65  Kumari 2019,66  Langley 1998,68  Mason 2000,69  Menon 2012,71  Menon 2014,72  Mwangi 2017a,75  Nieminen 2015,76  Norris 2010,77  Papaz 2012,79  Paquette 2019,80  Read 2009,81  Shah 2018a,23  Shilling 2009,84  Snowdon 2006,86  Surun 2018,88  Tait 1998,91  Tait 2003a,89  Tait 2004a,90  Thomas 2013,93  Volkening 2017,95  Ward 2009,96  Woodgate 2010,97  Woolfall 2013,98  Zupancic 1997a.24  
Negative impact on medical care 21 Barakat 2014,33  Baxter 2012,35  Braga 2014,36  Buck 2015,37  Clausen 1954,40  D'Amanda 2019,41  Elemraid 2013,45  Gattuso 2006,46  Genetti 2019,47  Gonzalez 2016,49  Helgesson 2009,54  Hoberman 2013a,55  Ingersgaard 2018,60  Menon 2014,72  Mihrshahi 2002,73  Morley 2005,74  Sureshkumar 2012,87  Tait 1998,91  Tait 2003a,89  Taylor 2015,92  Woolfall 2013.98  
Lack of direct benefit to child 16 Barakat 2014,33  Bartlett 2018,34  Clausen 1954,40  D'Amanda 2019a,41  Gattuso 2006,46  Genetti 2011,47  Gill 2014,48  Greenberg 2017,50  Helgesson 2009,54  Howard Sharp 2020,58  Kick 2018,64  Menon 2014,72  Mihrshahi 2002,73  Read 2009,81  Skinner 2011,85  Sureshkumar 2012.87  
Child's own medical concerns Chappuy 2006,39  Hulst 2005,59  Menon 2014,72  Mihrshahi 2002,73  Morley 2005,74  Sureshkumar 2012,87  Taylor 2015,92  Thomas 2013,93  Woodgate 2010.97  
Phlebotomy concerns 14 Chantler 2007,38  D'Amanda 2019a,41  Dlugos 2005,42  Helgesson 2009,54  Jay 2007a,61  Jenkins 2009,62  Kick 2018,64  Labib 2018,67  Mazzocco 1999,70  Menon 2012,71  Menon 2014,72  Scollon 2014,83  Vecchi 2013,94  Wynn 2010.99  
Burdens Logistics or burden of participation 35 Bartlett 2018,34  Baxter 2012,35  Chappuy 2006,39  D'Amanda 2019a,41  Gattuso 2006,46  Genetti 2019,47  Gill 2014,48  Gonzalez 2016,49  Greenberg 2017,50  Harth 1990,51  Hayman 2001,53  Helgesson 2009,54  Hoehn 2009,56  Hulst 2005,59  Jenkins 2009,62  Kick 2018,64  Korotchikova 2010,65  Langley 1998,68  Mason 2000,69  Mazzocco 1999,70  Mihrshahi 2002,73  Papaz 2012,79  Paquette 2019,80  Read 2009,81  Shilling 2009,84  Skinner 2011,85  Sureshkumar 2012,87  Tait 1998,91  Tait 2003a,89  Taylor 2015,92  Vecchi 2013,94  Volkening 2017,95  Woolfall 2013,98  Wynn 2010,99  Zupancic 1997a.24  
Lack of trust Lack of trust in clinicians Chappuy 2006.39  
Lack of trust in medical researchers Greenberg 2017,50  Helgesson 2009,54  Mason 2000,69  Read 2009,81  Shah 2018a,23  Wynn 2010.99  
Lack of trust in particular institution Harth 1990,51  Morley 2005.74  
Lack of trust in medicine in general Buck 2015,37  Harth 1990.51  
Lack of trust in research Chantler 2007,38  Dreyzin 2014,43  Mazzocco 1999,70  Snowdon 2006.86  
General research concerns Lack of interest in research 18 Braga 2014,36  Elemraid 2013,45  Gattuso 2006,46  Genetti 2019,47  Gonzalez 2016,49  Harth 1990,51  Hulst 2005,59  Langley 1998,68  Mazzocco 1999,70  Menon 2012,71  Menon 2014,72  Mihrshahi 2002,73  Morley 2005,74  Papaz 2012,79  Sammons 2007,82  Skinner 2011,85  Taylor 2015,92  Volkening 2017.95  
Guinea pig concerns Buck 2015,37  Chantler 2007,38  Clausen 1954,40  Greenberg 2017,50  Hoehn 2005,56  Korotchikova 2010,65  Shah 2018a,23  Tait 1998.91  
Privacy concerns 12 Gattuso 2006,46  Genetti 2019,47  Gill 2014,48  Harth 1990,51  Howard Sharp 2020,58  Kick 2018,64  Kumari 2019,66  Menon 2012,71  Papaz 2012,79  Sammons 2007,82  Scollon 2014,83  Tait 2004.90  
Lack of belief in research Helgesson 2009,44  Hulst 2005,59  Labib 2018,67  Nieminen 2015,76  Taylor 2015,92  Tait 1998a.91  
Discomfort with randomization 18 Braga 2014,54  Buck 2015,37  Eiser 2005,76  Gonzalez 2016,49  Greenberg 2017,50  Hoberman 2013a,55  Ingersgaard 2018,60  Jollye 2009,63  Kick 2018,64  Nieminen 2015,76  Norris 2010,77  Sammons 2007,82  Snowdon 2006,86  Surun 2018,88  Tait 1998,91  Woodgate 2010,97  Woolfall 2013,98  Wynn 2010.99  
Genetic testing concerns Genetti 2019,47  Howard Sharp 2020,58  Papaz 2012,79  Scollon 2014,83  Skinner 2011.85  
Informational and consent process related Not enough information provided about study; inadequate understanding of study 16 Barakat 2014,33  Chappuy 2006,39  Dahan 2020,22  Dreyzin 2014,43  Eiser 2005,44  Gill 2014,48  Helgesson 2009,54  Hoberman 2013a,55  Korotchikova 2010,65  Menon 2012,71  Menon 2014,72  Mwangi 2017a,75  Paquette 2019,80  Read 2009,81  Tait 2003a,89  Tait 2004.90  
Not enough time to make decision about enrollment 13 Barakat 2014,33  Chappuy 2006,39  Eiser 2005,44  Hoehn 2009a,56  Jollye 2009,63  Menon 2012,71  Papaz 2012,79  Paquette 2019,80  Snowdon 2006,86  Tait 1998,91  Tait 2004,90  Thomas 2013,93  Ward 2009.96  
Not enough knowledge about medical condition or lack of comfort with clinical decision Mazzocco 1999,70  Read 2009a.81  
Decision too stressful 29 Dahan 2020,22  Dlugos 2005,42  Genetti 2019,47  Greenberg 2017,50  Hoberman 2013a,55  Howard Sharp 2020,58  Hulst 2005,59  Ingersgaard 2018,60  Jollye 2009,63  Labib 2018,67  Mason 2000,69  Menon 2012,71  Menon 2014,72  Norris 2010,77  Papaz 2012,79  Paquette 2019,80  Read 2009,81  Sammons 2007,82  Scollon 2014,83  Shah 2018a,23  Snowdon 2006,86  Tait 1998a,91  Tait 2003a,90  Tait 2004,89  Thomas 2013,93  Ward 2009,96  Woodgate 2010,97  Woolfall 2013,98  Zupancic 1997a.24  
Parental perception of illness 10 Barakat 2014,33  Bartlett 2018,34  Buck 2015,37  Chantler 2007a,38  Clausen 1954,40  D'Amanda 2019a,41  Dreyzin 2014a,43  Jollye 2009,63  Wynn 2010,99  Zupancic 1997a.24  
Language barrier Helgesson 2009,54  Papaz 2012.79  
Prior experience or lack of experience with research 13 Chantler 2007a,38  Dahan 2020,22  Gonzalez 2016,49  Hulst 2005,59  Menon 2012,71  Menon 2014,72  Nieminen 2015a,76  Paquette 2019a,80  Shah 2018a,23  Tait 1998a,91  Tait 2003a,90  Tait 2004,89  Thomas 2013a.93  
Relational Discomfort with proxy nature of consent Chantler 2007,38  Papaz 2012,79  Woodgate 2010.97  
One parent wanted to enroll, other did not Dahan 2020,22  Genetti 2019,47  Hoehn 2009,56  Jenkins 2009,62  Korotchikova 2010a,65  Langley 1998,68  Menon 2014,72  Skinner 2011.85  
Family problems Baxter 2012,35  Chantler 2007,38  Jay 2007a,61  Menon 2012,71  Mihrshahi 2002.73  
Feeling pressured Hayman 2001a,53  Mason 2000.69  
Child's wishes related to enrollment 15 Chantler 2007,38  Chappuy 2006,39  Clausen 1954,40  Gill 2014,48  Greenberg 2017,50  Howard Sharp 2020,58  Hulst 2005,59  Ingersgaard 2018,60  Jay 2007a,61  Menon 2014,72  Shilling 2009,84  Sureshkumar 2012,87  Tait 2003a,90  Woodgate 2010,97  Woolfall 2013.98  
Decision-making style Hoberman 2013a55  
a

Study directly compared by enrollment status. See Table 9 for more details.

TABLE 9

Comparison of Barriers for Participation in Pediatric Research Between Participants and Nonparticipants

CategoryBarrierStudyDiscussionStatistics
Concerns about study participation Risk to child Clausen 1954d,40  More mothers who gave consent (82%) than mothers who withheld consent (18%) reported being “completely convinced that the shots will be perfectly safe” NA 
D’Amanda 2019d,41  More parents who declined enrollment than those who enrolled reported perceiving study as high risk NA 
dMore decliners (4/15) than joiners (1/16) expressed concerns that the experimental drug would be ineffective or have side effects NA 
Hayman 2001d,53  More declining parents (29%) than consenters (13%) were concerned about safety of test NA 
Hoberman 2013e,55  Nonconsenters were more likely than consenters to cite the “risk of being in the study” as a barrier to participation P < .001 
Mwangi 2017d,75  More decliners (8/15) than participants (1/20) “discussed potential risks to child of participating” NA 
Shah 2018d,23  Decliners (43/58) were less likely than enrollers (90/105) to rate “the possible risks associated with Epo” as “very important or important” to their decision making P = .09 
Tait 2003e,89  Nonconsenters had higher perception of study risk (4.3 on scale of 1–10) than consenters (1.5) P < .001 
Tait 2004e,90  Nonconsenters were more likely than consenters to view the risk-benefit ratio as higher P < .001 
Zupancic 1997e,24  Nonconsenters assessed study as of higher risk and lower benefit compared with consenters P < .0001 
Negative impact on medical care Hoberman 2013e,55  Nonconsenters were more likely than consenters to cite concern that the “study would interfere with the standard care” P < .001 
Tait 2003e89  Nonconsenters (47.2%) were more concerned than consenters (8%) that participation would affect child's care P < .0001 
Lack of direct benefit to child D’Amanda 2019d,41  More decliners (11/15) than joiners (2/16) had no expectation of individual benefit NA 
Phlebotomy concerns D’Amanda 2019b,41  More joiners (9/16) than decliners (4/15) cited blood draw requirements as a barrier NA 
Jay 2007e,61  Nonconsenters were more likely than consenters to worry about their child having a blood test P = .002 
Burdens Logistics or burden of participation D’Amanda 2019d,41  More decliners (15/15) than joiners (5/16) cited logistical inconvenience as a concern NA 
Tait 2003e,89  Nonconsenters (44.6%) were more likely than consenters (8.6%) to view the study as “just another thing to worry about” P < .0001 
Zupancic 1997d,24  More nonconsenters (22%) than consenters (10%) agreed or strongly agreed that “the process was too complex” NA 
Lack of trust Lack of trust in medical researchers Shah 2018e,23  Decliners (6/56) were more likely than enrollers (0/103) to report “not trusting” the person who approached them P = .001 
General research concerns Guinea pig concerns Shah 2018c,23  Decliners (38/58) did not differ from enrollers (61/105) in rating “the thought of my child being experimented on” as “very important or important” P = .21 
Lack of belief in research Tait 1998e,91  Nonconsenters were more likely than consenters to have “no opinion” about medical research P < .01 
Discomfort with randomization Hoberman 2013e,55  Nonconsenters were more likely than consenters to cite randomization as a barrier to participation P < .004 
eNonconsenters were more likely than consenters to cite parent blinding as a barrier to participation P < .001 
Informational and consent process related Not enough information provided about study; inadequate understanding of study Hoberman 2013c,55  Consent document characteristics were not different between consenters and nonconsenters P = .30 
 cConsent environment was not different between consenters and nonconsenters P = .19 
Mwangi 2017b,75  More decliners (11/15) than participants (2/20) “demonstrated an understanding of the trial as experimental” NA 
Tait 2003e,89  Non-consenters (59%) were less likely than consenters (89%) to believe they had been given “just the right amount of information” P < .0001 
  eeeeee Nonconsenters (34.9%) were more likely than consenters (8.8%) to believe they had been given “too little” information P < .0001 
Nonconsenters (44.2%) were less likely than consenters (63%) to think the information was “very clear” P < .0001 
Nonconsenters had lower scores on understanding of the study (19.4 on scale 5–25) compared with consenters (21.4) P < .001 
Nonconsenters (59%) were less likely than consenters (89%) to believe that they had been given “just the right amount of information” P < .0001 
Nonconsenters (34.9%) were less likely than consenters (8.8%) to believe they had been given “too little” information P < .0001 
Nonconsenters (44.2%) were less likely than consenters (63%) to think that the information was “very clear” P < .0001 
Not enough time to make decision about enrollment Hoehn 2009d,57  Fewer nonconsenters than consenter perceived adequacy of time to make decision NA 
Not enough knowledge about medical condition or lack of comfort with clinical decision Read 2009c,81  Enrollment rate did not differ based on “comfort with the medical language.” P = NS 
Decision too stressful Hoberman 2013e,55  Nonconsenters reported more anxiety about decision and difficulty making the decision than consenters P < .001 
 eNonconsenters had higher “uncertainty” scores than consenters P < .001 
Shah 2018e,23  Decliners (21.9 on scale 0–100) had higher decisional conflict scores than enrollers (17.2) P = .03 
Tait 2003e,89  Nonconsenters (31.2%) were more likely than consenters (8.8%) to report being anxious as a result of being asked to have their child participate P < .0001 
e Nonconsenters had greater decisional uncertainty (7.2 on scale 3–15) than consenters (6.2) P < .001 
c Nonconsenters had similar anxiety score (7.3 on scale 1–10) compared with consenters (6.5) P = NS 
Tait 1998e,91  Nonconsenter (21.1%) were less likely than consenters (6%) to report that the researcher seeking consent had made them feel more anxious P < .01 
Zupancic 1997d,24  More nonconsenters (6%) than consenters (3%) reported feeling pressure to consent NA 
Parental perception of illness Chantler 2007d,38  More parents who enrolled than who declined enrollment reported perceiving their child as healthy and able to handle the study procedures NA 
D’Amanda 2019d,41  More decliners (53%) than joiners (19%) cited autism as a comorbidity factor as a barrier NA 
Dreyzin 2014b,43  More decliners (1/1) than consenters (0/5) “perceived their child's health as relatively stable” NA 
Zupancic 1997c,24  Parental perceptions of illness severity were similar between consenters and non-consenters NA 
Prior experience with research or the medical system Chantler 2007c,38  Variable familiarity with science and medicine was seen in both parents who enrolled and those who declined enrollment NA 
Nieminen 2015a,76  Nonconsenters (282/356) were more likely than consenters (642/965) to report no previous experience with medical trials P < .001 
Paquette 2019b,80  There was increased enrollment among those with prior research participation P = .08 
Shah 2018c,23  Decliners did not differ from enrollers in prior research participation P = NS 
Tait 2003c,89  Nonconsenters (18.3%) did not differ from consenters (20.0%) in prior research experience of the child P = NS 
c Nonconsenters (21.5%) did not differ from consenters (24.4%) in prior research experience of the parent P = NS 
Thomas 2013c,93  Past experience with research was seen in both parents who enrolled and those who declined enrollment NA 
Tait 1998a,91  Nonconsenters were less likely to have had their child participate in a previous study P < .05 
Relational One parent wanted to enroll, other did not Korotchikova 2010e,65  Parents were more likely to consent if both parents were present (96%) compared with when only mother was present (53%) P < .0001 
Family problems Jay 2007e,61  Nonconsenters were more likely than consenters to report a “presence of other personal reasons” P = .0001 
Feeling pressured Hayman 2001b,53  Fewer decliners (2%) than consenters (5%) reported feeling pressured into taking part in study NA 
Child's wishes related to enrollment Jay 2007d,61  More nonconsenters than consenters to “reported that discussing the follow-up [requirements] with their child influenced their decision to participate” NA 
eTait 2003c,89  Nonconsenters (67%) were no more likely than consenters (48%) to state that their child influenced their decision P = NS 
Decision -making style Hoberman 2013c,55  Decision making style (family or self versus shared with doctor) did not differ between consenters and non-consenters P = NS 
CategoryBarrierStudyDiscussionStatistics
Concerns about study participation Risk to child Clausen 1954d,40  More mothers who gave consent (82%) than mothers who withheld consent (18%) reported being “completely convinced that the shots will be perfectly safe” NA 
D’Amanda 2019d,41  More parents who declined enrollment than those who enrolled reported perceiving study as high risk NA 
dMore decliners (4/15) than joiners (1/16) expressed concerns that the experimental drug would be ineffective or have side effects NA 
Hayman 2001d,53  More declining parents (29%) than consenters (13%) were concerned about safety of test NA 
Hoberman 2013e,55  Nonconsenters were more likely than consenters to cite the “risk of being in the study” as a barrier to participation P < .001 
Mwangi 2017d,75  More decliners (8/15) than participants (1/20) “discussed potential risks to child of participating” NA 
Shah 2018d,23  Decliners (43/58) were less likely than enrollers (90/105) to rate “the possible risks associated with Epo” as “very important or important” to their decision making P = .09 
Tait 2003e,89  Nonconsenters had higher perception of study risk (4.3 on scale of 1–10) than consenters (1.5) P < .001 
Tait 2004e,90  Nonconsenters were more likely than consenters to view the risk-benefit ratio as higher P < .001 
Zupancic 1997e,24  Nonconsenters assessed study as of higher risk and lower benefit compared with consenters P < .0001 
Negative impact on medical care Hoberman 2013e,55  Nonconsenters were more likely than consenters to cite concern that the “study would interfere with the standard care” P < .001 
Tait 2003e89  Nonconsenters (47.2%) were more concerned than consenters (8%) that participation would affect child's care P < .0001 
Lack of direct benefit to child D’Amanda 2019d,41  More decliners (11/15) than joiners (2/16) had no expectation of individual benefit NA 
Phlebotomy concerns D’Amanda 2019b,41  More joiners (9/16) than decliners (4/15) cited blood draw requirements as a barrier NA 
Jay 2007e,61  Nonconsenters were more likely than consenters to worry about their child having a blood test P = .002 
Burdens Logistics or burden of participation D’Amanda 2019d,41  More decliners (15/15) than joiners (5/16) cited logistical inconvenience as a concern NA 
Tait 2003e,89  Nonconsenters (44.6%) were more likely than consenters (8.6%) to view the study as “just another thing to worry about” P < .0001 
Zupancic 1997d,24  More nonconsenters (22%) than consenters (10%) agreed or strongly agreed that “the process was too complex” NA 
Lack of trust Lack of trust in medical researchers Shah 2018e,23  Decliners (6/56) were more likely than enrollers (0/103) to report “not trusting” the person who approached them P = .001 
General research concerns Guinea pig concerns Shah 2018c,23  Decliners (38/58) did not differ from enrollers (61/105) in rating “the thought of my child being experimented on” as “very important or important” P = .21 
Lack of belief in research Tait 1998e,91  Nonconsenters were more likely than consenters to have “no opinion” about medical research P < .01 
Discomfort with randomization Hoberman 2013e,55  Nonconsenters were more likely than consenters to cite randomization as a barrier to participation P < .004 
eNonconsenters were more likely than consenters to cite parent blinding as a barrier to participation P < .001 
Informational and consent process related Not enough information provided about study; inadequate understanding of study Hoberman 2013c,55  Consent document characteristics were not different between consenters and nonconsenters P = .30 
 cConsent environment was not different between consenters and nonconsenters P = .19 
Mwangi 2017b,75  More decliners (11/15) than participants (2/20) “demonstrated an understanding of the trial as experimental” NA 
Tait 2003e,89  Non-consenters (59%) were less likely than consenters (89%) to believe they had been given “just the right amount of information” P < .0001 
  eeeeee Nonconsenters (34.9%) were more likely than consenters (8.8%) to believe they had been given “too little” information P < .0001 
Nonconsenters (44.2%) were less likely than consenters (63%) to think the information was “very clear” P < .0001 
Nonconsenters had lower scores on understanding of the study (19.4 on scale 5–25) compared with consenters (21.4) P < .001 
Nonconsenters (59%) were less likely than consenters (89%) to believe that they had been given “just the right amount of information” P < .0001 
Nonconsenters (34.9%) were less likely than consenters (8.8%) to believe they had been given “too little” information P < .0001 
Nonconsenters (44.2%) were less likely than consenters (63%) to think that the information was “very clear” P < .0001 
Not enough time to make decision about enrollment Hoehn 2009d,57  Fewer nonconsenters than consenter perceived adequacy of time to make decision NA 
Not enough knowledge about medical condition or lack of comfort with clinical decision Read 2009c,81  Enrollment rate did not differ based on “comfort with the medical language.” P = NS 
Decision too stressful Hoberman 2013e,55  Nonconsenters reported more anxiety about decision and difficulty making the decision than consenters P < .001 
 eNonconsenters had higher “uncertainty” scores than consenters P < .001 
Shah 2018e,23  Decliners (21.9 on scale 0–100) had higher decisional conflict scores than enrollers (17.2) P = .03 
Tait 2003e,89  Nonconsenters (31.2%) were more likely than consenters (8.8%) to report being anxious as a result of being asked to have their child participate P < .0001 
e Nonconsenters had greater decisional uncertainty (7.2 on scale 3–15) than consenters (6.2) P < .001 
c Nonconsenters had similar anxiety score (7.3 on scale 1–10) compared with consenters (6.5) P = NS 
Tait 1998e,91  Nonconsenter (21.1%) were less likely than consenters (6%) to report that the researcher seeking consent had made them feel more anxious P < .01 
Zupancic 1997d,24  More nonconsenters (6%) than consenters (3%) reported feeling pressure to consent NA 
Parental perception of illness Chantler 2007d,38  More parents who enrolled than who declined enrollment reported perceiving their child as healthy and able to handle the study procedures NA 
D’Amanda 2019d,41  More decliners (53%) than joiners (19%) cited autism as a comorbidity factor as a barrier NA 
Dreyzin 2014b,43  More decliners (1/1) than consenters (0/5) “perceived their child's health as relatively stable” NA 
Zupancic 1997c,24  Parental perceptions of illness severity were similar between consenters and non-consenters NA 
Prior experience with research or the medical system Chantler 2007c,38  Variable familiarity with science and medicine was seen in both parents who enrolled and those who declined enrollment NA 
Nieminen 2015a,76  Nonconsenters (282/356) were more likely than consenters (642/965) to report no previous experience with medical trials P < .001 
Paquette 2019b,80  There was increased enrollment among those with prior research participation P = .08 
Shah 2018c,23  Decliners did not differ from enrollers in prior research participation P = NS 
Tait 2003c,89  Nonconsenters (18.3%) did not differ from consenters (20.0%) in prior research experience of the child P = NS 
c Nonconsenters (21.5%) did not differ from consenters (24.4%) in prior research experience of the parent P = NS 
Thomas 2013c,93  Past experience with research was seen in both parents who enrolled and those who declined enrollment NA 
Tait 1998a,91  Nonconsenters were less likely to have had their child participate in a previous study P < .05 
Relational One parent wanted to enroll, other did not Korotchikova 2010e,65  Parents were more likely to consent if both parents were present (96%) compared with when only mother was present (53%) P < .0001 
Family problems Jay 2007e,61  Nonconsenters were more likely than consenters to report a “presence of other personal reasons” P = .0001 
Feeling pressured Hayman 2001b,53  Fewer decliners (2%) than consenters (5%) reported feeling pressured into taking part in study NA 
Child's wishes related to enrollment Jay 2007d,61  More nonconsenters than consenters to “reported that discussing the follow-up [requirements] with their child influenced their decision to participate” NA 
eTait 2003c,89  Nonconsenters (67%) were no more likely than consenters (48%) to state that their child influenced their decision P = NS 
Decision -making style Hoberman 2013c,55  Decision making style (family or self versus shared with doctor) did not differ between consenters and non-consenters P = NS 

NA, not applicable; NS, not significant.

a

Significantly associated with enrolling (quantitative only: P < .05)

b

Tends toward enrolling (quantitative: [P ≥ .05 and P ≤ .1] or qualitative)

c

No difference (quantitative or qualitative)

d

Tends toward declining (quantitative: (P ≥ .05 and P ≤ .1) or qualitative)

e

Significantly associated with declining (quantitative only: P < .05)

Concerns About Study Participation

Concerns about study participation emerged as an important category of barriers to enrollment. Here we included only direct negative impacts of research participation. These included risk to child, negative impact on patient care, lack of direct benefit to child, the child’s own medical concerns, and phlebotomy concerns. The most frequently mentioned barriers to study participation in this category were risk to child (N = 46), negative impact on medical care (N = 21) and lack of direct benefit to child (N = 16). In each of these, all studies comparing by enrollment status identified a negative association between the barrier and enrollment. Nine studies reported the child’s own medical concerns (eg, the child does not know their true diagnosis or prognosis) as a barrier to enrollment, though none compared by enrollment status. Fourteen studies reported phlebotomy concerns as a barrier to enrollment; this was variably associated with enrollment.

Burdens

Burdens of participation were identified as barriers to pediatric research participation. Within this category, we included the logistical burden of participation. Studies frequently reported the logistical burden of participation (N = 35) as a barrier to enrollment; this was the second most reported barrier in any category surpassed only by risk to child. All 3 studies that reported the logistical burden of participation as a barrier found a negative association with this barrier and enrollment.

Lack of Trust

Lack of trust, distrust, and mistrust were important barriers to enrollment. Because of the heterogeneity of how these terms were defined and used, we did not distinguish between them. We did differentiate between the object of low trust: lack of trust in medical researchers (N = 6), lack of trust in medical research (N = 4), lack of trust in a particular institution (N = 2), lack of trust in medicine in general (N = 2), and lack of trust in clinicians (N = 1). The single study that compared by enrollment status found that lower trust in medical research was associated with lower enrollment.

General Research Concerns

Another important theme of barriers to enrollment was general concern with research. Within this category, we included: lack of interest in research, concern over their child being a “guinea pig,” privacy concerns, lack of belief in research, discomfort with randomization, and genetic testing concerns. Whereas there is some overlap between lack of interest in research and lack of belief in research, there was enough distinction to create separate barriers. Lack of interest captured a current lack of interest in research, whereas lack of belief reflected a moral objection or belief that research does not work in general. Definitions and examples are provided in Table 5. Studies frequently reported lack of interest in research (N = 18), discomfort with randomization (N = 18) and lack of belief in research (N = 6) as barriers; all studies that compared by enrollment status found a negative association with the barrier. Twelve studies reported privacy concerns, but none compared by enrollment status.

Informational and Consent Process Related

Concerns related to the consent process or information sharing emerged as important barriers to enrollment. This large category included 7 items (Table 5). Studies frequently reported these barriers to enrollment: inadequate understanding of study (N = 16), not enough time to make decision (N = 13), and decision being too stressful (N = 29). For each of these, most studies that compared by enrollment status found a negative association between the barrier and enrollment. Ten studies found that parent perception of illness was a barrier to enrollment. In the 4 studies that compared by enrollment status, the barrier was variably associated with enrollment: 2 studies found that lower parental perception of illness was associated with lower enrollment, 1 study found that lower parent perception of illness was associated with higher enrollment, and 1 study found no association.

Relational

Concerns related to parental relationships emerged as barriers to enrollment. These included 6 items (Table 5). Most commonly reported were child’s wishes to not participate (N = 15) and differing preferences between parents (N = 8). Few studies compared these items directly by enrollment status.

Changes Over Time

Barriers to research were examined across decades to see if any changes emerged. The most cited barriers to enrollment in each of these 3 epochs (1990s, 2000s, 2010s) were logistical burdens (N = 5, N = 11, N = 19), risk to child (N = 4, N = 14, N = 26), and the decision being too stressful (N = 2, N = 10, N = 15). These 3 categories were similarly cited over time, however 2 less cited categories had more citations in the most recent cohort: discomfort with randomization (N = 1, N = 4, N = 13) and concerns related to negative impact on medical care (N = 1, N = 5, N = 14).

Parental inclusion rates within the enrollment studies included in this review is challenging to interpret because of variable reporting. Several studies (N = 7) did not report the number of included parents. The studies that did report included parents often did not report number of parents eligible but not included in the enrollment study.

However, 2 notable trends emerged from the available data (Table 10). First, inclusion rates varied drastically by type of enrollment study: surveys and interviews included less than half of eligible parents, whereas recruitment log studies included more than 90%. Second, inclusion rates varied by enrollment status, with greater inclusion among parents who enrolled in the feeder study compared with those who declined participation in the feeder study.

TABLE 10

Overall Enrollment Rate and Population Size of Enrollment Studies

Enrollment Study TypeManuscriptsEnrolled in Feeder StudyDeclined Enrollment in Feeder Study
N Included in Enrollment StudyN Included or Eligible (%) for Enrollment StudyN Included in Enrollment StudyN Included or Eligible (%) for Enrollment Study
Survey and interview studies 46a 5800 3044/6174 (49%)b 2239 1394/3846 (36%)b 
Recruitment log studies 24 10 218 10 218/10 551 (97%)c 15 495 15 403/17 175 (90%)c 
All studies 70 16 018 13 262/16 725 (79%)d 17 734 16 797/21 021 (80%)d 
Enrollment Study TypeManuscriptsEnrolled in Feeder StudyDeclined Enrollment in Feeder Study
N Included in Enrollment StudyN Included or Eligible (%) for Enrollment StudyN Included in Enrollment StudyN Included or Eligible (%) for Enrollment Study
Survey and interview studies 46a 5800 3044/6174 (49%)b 2239 1394/3846 (36%)b 
Recruitment log studies 24 10 218 10 218/10 551 (97%)c 15 495 15 403/17 175 (90%)c 
All studies 70 16 018 13 262/16 725 (79%)d 17 734 16 797/21 021 (80%)d 
a

Includes 7 studies that did not describe enrollment numbers.

b

Includes the 16 out of 46 manuscripts that reported N eligible for the enrollment study.

c

Includes the 23 out of 24 manuscripts that reported N eligible for the enrollment study.

d

Includes the 39 out of 70 manuscripts that reported N eligible for the enrollment study.

In this review of barriers and facilitators to research participation in pediatrics, our findings suggest several conclusions we will discuss. First, health benefit to child and altruism emerged as the most consistent motivators for study participation. Second, leading barriers to enrollment were a potential risk to child and the burdens of participation. Third, parental perception of illness was associated with enrollment in complex ways. Fourth, even with a review methodology that prioritized identifying the views of research decliners, the information available from this elusive population was limited. Lastly, we will consider how societal events in recent years may contribute to changes in the importance of facilitators and barriers to pediatric research participation.

Health benefit to child and altruism were the most identified facilitators to research participation. This is consistent with an earlier review, which also identified personal health benefit for child and altruism as the most cited motivating factors for enrollment.26  The relationship between perceived health benefit to child and research participation is an ethically fraught and complicated one. If parental perception of health benefit to child results in increased enrollment, then researchers should promote the health benefits of research participation. However, this may be problematic if the perception of benefit is incorrect. Sometimes, participation in research may result in health benefits to the child, such as access to an intervention otherwise unavailable.100  More often, however, there may not be a direct benefit to the child, or the potential for direct benefit may be uncertain.14  Our methods are not able to determine how much such a belief in potential benefit to your child may overlap with the therapeutic misconception in which research participants believe that the goal of research is to benefit participants, rather than to generate generalizable knowledge.101  This may be particularly problematic in high-stakes scenarios.102  Future work must access ways to harness this facilitator of research participation without misleading parents considering research for their child.

Altruism emerged as another strong facilitator to research participation. There is a growing body of literature suggesting that multiple kinds of altruism may exist. Research altruism may be a specific kind of altruism different from other types.103  Others have proposed a phenomenon of “conditional altruism,” which may prime interest in research participation but is not sufficient to result in participation without other factors.104  The included manuscripts do not shed light on whether research participation related altruism may be a modifiable factor. Future work should identify how altruism may be harnessed to optimize participation within pediatric research.

The potential risk to child emerged as the most mentioned barrier to participation. Tromp similarly found that fear of risks is the most frequent discouraging factor to participation in clinical trials.26  Medical risks of study participation was the most cited reason for those declining an adult statin clinical trial105  and a pediatric sickle cell clinical trial.106  This suggests the need for improvements in how researchers inform parents of potential risks to child and in strategies to effectively address parental concerns.

Burden of participation was the second most frequently cited barrier, followed closely by concerns that the decision was too stressful. This is consistent with a review of qualitative studies asking adult research participants (excluding decliners) about their experiences that found that the psychological burdens of participation were substantial and were present through all parts of the research process.107  A review of qualitative studies of adult research participants and decliners identified wariness of additional burden of research participation as a major theme.108  Researchers may find it beneficial to consider methods to mitigate burdens of participation, both psychological and logistical, to improve recruitment in clinical trials. These may include assistance or reimbursement for travel, childcare, use of virtual research visits or home visits, coordination of study visits and laboratory draws with other clinic appointments, and increased availability of translation services. Such efforts have the potential to ease the burden of a clinical trial with the potential to increase participation. Importantly, these burdens are most impactful for under-represented populations or for those with limited access to resources. Addressing burdens must be approached with the goal of decreasing inequities in research participation.

Parental perception of illness emerged as a barrier that was associated with enrollment status in complex ways. Illness perception is a complex phenomenon, impacted not only by clinical situation but by interpretation of that situation by a parent, which is likely impacted by many things, including health status, familiarity with the disease, and personal factors, such as coping mechanisms. In a study assessing participation in research related to pediatric diabetic ketoacidosis, severity was not associated with enrollment status, but parents of children with previous episodes of ketoacidosis were more likely to enroll in the study than those without past events.109  We found that perception that a child is very ill might serve as either a facilitator or a barrier to enrollment. Fragile or worsening health might be a barrier when a parent perceives the child is not in adequate health to assume the risks of the study. Alternatively, parental perception that a child is in poor or deteriorating health might facilitate trial participation when a parent believes the study may provide a cure or successful treatment of their sick child.110  Further studies regarding factors that determine parental perception of illness and how risk and benefit are viewed, in light of this perception, could increase trial participation.

Although our methods aimed to prioritize research decliners, the data we identified from this population represented well under half of the included population, which limited our ability to directly compare parents who declined pediatric research with those who enrolled their child. This was true for several reasons. First, many studies included far greater numbers of parents who enrolled their child compared with parents who declined participation. Second, many studies that did include higher numbers of decliners reported less useful data from them (eg, screening log reports only) that did not allow for robust analysis of potential facilitators and barriers. Lastly, the methods of many of the included studies did not allow for direct comparison between enrolled and declined parents. For example, some studies only asked those who enrolled about facilitators and only asked those who declined about barriers. Future studies that ask precisely the same questions to parents regardless of enrollment status will enable better understanding of the reasons parents choose to enroll or decline participation in pediatric research.

Lastly, we would like to acknowledge that recent significant societal events may be influencing facilitators and barriers to pediatric research participation. These include but are not limited to: the murder of George Floyd and the Black Lives Matter movement,111  the coronavirus disease 2019 pandemic,112  increasing political polarization,113  global wars,114  and the increasing impact of climate change.115,116  The results from this review revealed no clear trends in the most cited barriers and facilitators in the 1990s, 2000s, and 2010s. However, there is a delay between change in attitudes and the report of such changes in the scientific literature, which precludes the current manuscript from evaluating the potential impact of recent societal events. It is possible, for example, that coronavirus disease 2019 vaccine and mask mandates may result in decreased trust of researchers and clinicians. Many of these events may erode public trust in the police, legal, and political systems, which may diminish trust in medical institutions. Altruistic motivation may be altered by local and global political turmoil. Future work should evaluate how these facilitators and barriers to pediatric research participation continue to change over time.

One limitation of our systematic review was that we only included studies in English. Additionally, because of the methods used by the included studies, we were unable to analyze the interactions between factors (eg, how altruism and benefits may together lead toward enrollment decisions) or to rank the relative importance of barriers of facilitators to research participation.

This systematic review offers a comprehensive overview of the barriers and facilitators to participation in pediatric research as reported in peer-reviewed articles. Health benefit to child and altruism emerged as the most cited facilitators. In addition, this review highlighted differences between parents who enroll their child in clinical research and parents who decline to do so.

The findings from this review may guide researchers aiming to create interventions to improve the parental experience of recruitment for pediatric studies and to optimize enrollment rates.

Future work should focus on parents who decline participation in pediatric research and should use methodologies that enable direct comparison between enrolled and declined parents. Additionally, further research is needed to analyze the interactions between barriers and facilitators to research participation, to determine the relative importance of each, and to evaluate how they may interact with other critical variables, such as parent demographics.

Study data were collected and managed using Research Electronic Data Capture (REDCap) electronic data capture tools hosted at the University of Washington.117,118  REDCap is a secure, web-based software platform designed to support data capture for research studies, providing (1) an intuitive interface for validated data capture; (2) audit trails for tracking data manipulation and export procedures; (3) automated export procedures for seamless data downloads to common statistical packages; and (4) procedures for data integration and interoperability with external sources. REDCap at the University of Washington is supported by Institute of Translational Health Science grant support (UL1 TR002319, KL2 TR002317, and TL1 TR002318 from NCATS/NIH).

We thank research librarian Peggy Cruse, MA, Seattle Children’s Hospital, for assistance performing our systematic review; Amanda Mercer, BA, Treuman Katz Center for Pediatric Bioethics, for literature review assistance; Sheila Ganti, PhD, Seattle Children’s Hospital, for assistance with REDCap creation; Megan Gray, MD, University of Washington, for assistance with data presentation; and Stephanie Kraft, JD, University of Washington, for critically reviewing a draft of the manuscript.

Dr Weiss conceptualized the study and designed the study; Dr Nathe designed the data collection instruments, collected data, conducted the analysis, and drafted the initial manuscript; Ms Oskoui designed the data collection instruments, collected data, and conducted the analysis; and all authors reviewed and revised the manuscript, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work.

FUNDING: This study was supported in part by the National Institutes of Health through the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K23HD103872). The funders had no control over design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The National Institutes of Health had no role in the design and conduct of this study.

CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no conflicts of interest relevant to this article to disclose.

PRISMA

Preferred Reporting Items for Systematic Review and Meta-analysis

1
Niemeyer
L
,
Mechler
K
,
Buitelaar
J
, et al
.
“Include me if you can”-reasons for low enrollment of pediatric patients in a psychopharmacological trial
.
Trials
.
2021
;
22
(
1
):
178
2
Revell
J
,
Backman
C
,
Vasily
S
,
Harrison
D
.
Challenges with recruitment in pediatric procedural pain research
.
Pediatric Pain Letter
.
2020
;
22
(
3
):
38
41
3
Afshar
K
,
Lodha
A
,
Costei
A
,
Vaneyke
N
.
Recruitment in pediatric clinical trials: an ethical perspective
.
J Urol
.
2005
;
174
(
3
):
835
840
4
Nicklin
S
,
Spencer
SA
.
Recruitment failure in early neonatal research
.
Arch Dis Child Fetal Neonatal Ed
.
2004
;
89
(
3
):
F281
5
Fischer
HS
,
Bührer
C
,
Czernik
C
.
Hazards to avoid in future neonatal studies of nasal high-frequency oscillatory ventilation: lessons from an early terminated trial
.
BMC Res Notes
.
2019
;
12
(
1
):
237
6
Lim
CS
,
Follansbee-Junger
KW
, %
Crawford
MS
,
Janicke
DM
.
Treatment outcome research in rural pediatric populations: the challenge of recruitment
.
J Pediatr Psychol
.
2011
;
36
(
6
):
696
707
7
Laventhal
N
,
Tarini
BA
,
Lantos
J
.
Ethical issues in neonatal and pediatric clinical trials
.
Pediatr Clin North Am
.
2012
;
59
(
5
):
1205
1220
8
Katz
AL
,
Webb
SA
.
Informed consent in decision-making in pediatric practice
.
Pediatrics
.
2016
;
138
(
2
):
e20161484
9
Nordheim
T
,
Anderzén-Carlsson
A
, %
Nakstad
B
.
A qualitative study of the experiences of Norwegian parents of very low birthweight infants enrolled in a randomized nutritional trial
.
J Pediatr Nurs
.
2018
;
43
:
e66
e74
10
Guttmann
KF
,
Wu
YW
,
Juul
SE
,
Weiss
EM
.
Consent related challenges for neonatal clinical trials
.
Am J Bioeth
.
2020
;
20
(
5
):
38
40
11
Al Maghaireh
DF
,
Abdullah
KL
, %
Chan
CM
,
Piaw
CY
,
Al Kawafha
MM
.
Systematic review of qualitative studies exploring parental experiences in the neonatal intensive care unit
.
J Clin Nurs
.
2016
;
25
(
19–20
):
2745
2756
12
Neyro
V
,
Elie
V
,
Thiele
N
,
Jacqz-Aigrain
E
.
Clinical trials in neonates: how to optimise informed consent and decision making? A European Delphi survey of parent representatives and clinicians
.
PLoS One
.
2018
;
13
(
6
):
e0198097
13
Rich
WD
,
Auten
KJ
,
Gantz
MG
, et al;
National Institute of Child Health and Human Development Neonatal Research Network
.
Antenatal consent in the SUPPORT trial: challenges, costs, and representative enrollment
.
Pediatrics
.
2010
;
126
(
1
):
e215
e221
14
Rich
W
,
Finer
NN
,
Gantz
MG
, et al;
SUPPORT and Generic Database Subcommittees of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
.
Enrollment of extremely low birth weight infants in a clinical research study may not be representative
.
Pediatrics
.
2012
;
129
(
3
):
480
484
15
Paskett
ED
,
Reeves
KW
,
McLaughlin
JM
, et al
.
Recruitment of minority and underserved populations in the United States: the Centers for Population Health and Health Disparities experience
.
Contemp Clin Trials
.
2008
;
29
(
6
):
847
861
16
Weiss
EM
,
Olszewski
AE
,
Guttmann
KF
, et al
.
Parental factors associated with the decision to participate in a neonatal clinical trial
.
JAMA Netw Open
.
2021
;
4
(
1
):
e2032106
17
Foglia
EE
,
Nolen
TL
,
DeMauro
SB
, et al;
Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
.
Short-term outcomes of infants enrolled in randomized clinical trials vs those eligible but not enrolled
.
JAMA
.
2015
;
313
(
23
):
2377
2379
18
Karvonen
KL
,
Baer
RJ
,
Rogers
EE
, et al
.
Racial and ethnic disparities in outcomes through 1 year of life in infants born prematurely: a population based study in California
.
J Perinatol
.
2021
;
41
(
2
):
220
231
19
Burris
HH
,
Duncan
AF
.
Rethinking how to persuade more parents from diverse or disadvantaged backgrounds to enroll infants in neonatal clinical trials
.
JAMA Netw Open
.
2021
;
4
(
1
):
e2032137
20
Svensson
K
,
Ramírez
OF
,
Peres
F
,
Barnett
M
,
Claudio
L
.
Socioeconomic determinants associated with willingness to participate in medical research among a diverse population
.
Contemp Clin Trials
.
2012
;
33
(
6
):
1197
1205
21
Gillies
K
,
Elwyn
G
,
Cook
J
.
Making a decision about trial participation: the feasibility of measuring deliberation during the informed consent process for clinical trials
.
Trials
.
2014
;
15
:
307
22
Dahan
S
,
Jung
C
,
Dassieu
G
, %
Durrmeyer
X
,
Caeymaex
L
.
Trust and consent: a prospective study on parents’ perspective during a neonatal trial
.
J Med Ethics
.
2020
;
47
(
10
):
678
683
23
Shah
AR
,
Wilfond
BS
,
Silvia
A
, et al;
PENUT Neonatal Informed Consent Working Group
.
Informed consent for a neonatal clinical trial: parental experiences and perspectives
.
J Perinatol
.
2018
;
38
(
7
):
865
872
24
Zupancic
JA
,
Gillie
P
,
Streiner
DL
,
Watts
JL
,
Schmidt
B
.
Determinants of parental authorization for involvement of newborn infants in clinical trials
.
Pediatrics
.
1997
;
99
(
1
):
E6
25
Weiss
EM
,
Guttmann
KF
,
Olszewski
AE
, et al
.
Parental enrollment decision-making for a neonatal clinical trial
.
J Pediatr
.
2021
;
239
:
143
149.e3
26
Tromp
K
,
Zwaan
CM
,
van de Vathorst
S
.
Motivations of children and their parents to participate in drug research: a systematic review
.
Eur J Pediatr
.
2016
;
175
(
5
):
599
612
27
Fisher
HR
,
McKevitt
C
,
Boaz
A
.
Why do parents enroll their children in research: a narrative synthesis
.
J Med Ethics
.
2011
;
37
(
9
):
544
551
28
Moher
D
,
Liberati
A
,
Tetzlaff
J
,
Altman
DG
,
Group
P
;
PRISMA Group
.
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement
.
PLoS Med
.
2009
;
6
(
7
):
e1000097
29
Nathe
J
,
Oskoui
T
,
Weiss
EM
.
What influences whether parents decide to enroll their children in pediatric research: a systematic review
.
30
Critical Appraisal Skills Programme
.
CASP checklists
.
Available at: https://casp-uk.net/casp-tools-checklists. Accessed January 10, 2022
31
Hawker
S
,
Payne
S
,
Kerr
C
,
Hardey
M
,
Powell
J
.
Appraising the evidence: reviewing disparate data systematically
.
Qual Health Res
.
2002
;
12
(
9
):
1284
1299
32
Cavolo
A
,
Dierckx de Casterlé
B
, %
Naulaers
G
,
Gastmans
C
.
Physicians' attitudes on resuscitation of extremely premature infants: a systematic review
.
Pediatrics
.
2019
;
143
(
6
):
e20183972
33
Barakat
LP
,
Schwartz
LA
,
Reilly
A
, %
Deatrick
JA
,
Balis
F
.
A qualitative study of phase III cancer clinical trial enrollment decision-making: perspectives from adolescents, young adults, caregivers, and providers
.
J Adolesc Young Adult Oncol
.
2014
;
3
(
1
):
3
11
34
Bartlett
A
,
Kolb
SJ
,
Kingsley
A
, et al;
NeuroNEXT Clinical Trial Network and on behalf of the NN101 SMA Biomarker Investigators
.
Recruitment & retention program for the NeuroNEXT SMA Biomarker Study: super babies for SMA!
Contemp Clin Trials Commun
.
2018
;
11
:
113
119
35
Baxter
J
,
Vehik
K
,
Johnson
SB
, %
Lernmark
B
,
Roth
R
,
Simell
T
;
TEDDY Study Group
.
Differences in recruitment and early retention among ethnic minority participants in a large pediatric cohort: the TEDDY Study
.
Contemp Clin Trials
.
2012
;
33
(
4
):
633
640
36
Braga
LH
,
Pemberton
J
,
Heaman
J
, %
DeMaria
J
,
Lorenzo
AJ
.
Pilot randomized, placebo controlled trial to investigate the effect of antibiotic prophylaxis on the rate of urinary tract infection in infants with prenatal hydronephrosis
.
J Urol
.
2014
;
191
(
5 Suppl
):
1501
1507
37
Buck
D
,
Hogan
V
,
Powell
CJ
, et al;
SamExo (Surgery versus Active Monitoring in Intermittent Exotropia) trial
.
Surrendering control, or nothing to lose: parents’ preferences about participation in a randomised trial of childhood strabismus surgery
.
Clin Trials
.
2015
;
12
(
4
):
384
393
38
Chantler
TE
,
Lees
A
,
Moxon
ER
,
Mant
D
,
Pollard
AJ
,
Fiztpatrick
R
.
The role familiarity with science and medicine plays in parents’ decision making about enrolling a child in vaccine research
.
Qual Health Res
.
2007
;
17
(
3
):
311
322
39
Chappuy
H
,
Doz
F
,
Blanche
S
,
Gentet
JC
,
Pons
G
,
Tréluyer
JM
.
Parental consent in paediatric clinical research
.
Arch Dis Child
.
2006
;
91
(
2
):
112
116
40
Clausen
JA
,
Seidenfeld
MA
,
Deasy
LC
.
Parent attitudes toward participation of their children in polio vaccine trials
.
Am J Public Health Nations Health
.
1954
;
44
(
12
):
1526
1536
41
D'Amanda
CS
,
Peay
HL
,
Wheeler
AC
,
Turbitt
E
,
Biesecker
BB
.
Fragile X syndrome clinical trials: exploring parental decision-making
.
J Intellect Disabil Res
.
2019
;
63
(
8
):
926
935
42
Dlugos
DJ
,
Scattergood
TM
,
Ferraro
TN
,
Berrettinni
WH
,
Buono
RJ
.
Recruitment rates and fear of phlebotomy in pediatric patients in a genetic study of epilepsy
.
Epilepsy Behav
.
2005
;
6
(
3
):
444
446
43
Dreyzin
A
,
Barnato
AE
,
Soltys
KA
, et al
.
Parent perspectives on decisions to participate in a phase I hepatocyte transplant trial
.
Pediatr Transplant
.
2014
;
18
(
1
):
112
119
44
Eiser
C
,
Davies
H
,
Jenney
M
,
Glaser
A
.
Mothers’ attitudes to the randomized controlled trial (RCT): the case of acute lymphoblastic leukaemia (ALL) in children
.
Child Care Health Dev
.
2005
;
31
(
5
):
517
523
45
Elemraid
M
,
Pollard
K
,
Thomas
M
, et al
.
Parental decisions on children participating in research
.
Nurs Child Young People
.
2013
;
25
(
8
):
16
21
46
Gattuso
J
,
Hinds
P
,
Tong
X
,
Srivastava
K
.
Monitoring child and parent refusals to enrol in clinical research protocols
.
J Adv Nurs
.
2006
;
53
(
3
):
319
326
47
Genetti
CA
,
Schwartz
TS
,
Robinson
JO
, et al
.
Parental interest in genomic sequencing of newborns: enrollment experience from the BabySeq project
.
Genet Med
.
2019
;
21
(
3
):
622
630
48
Gill
C
,
Ansermino
MJ
,
Sanatani
S
, %
Mulpuri
K
,
Doan
Q
.
Paediatric patient family engagement with clinical research at a tertiary care paediatric hospital
.
Paediatr Child Health
.
2014
;
19
(
10
):
537
542
49
Gonzalez
KW
,
Adibe
OO
,
Dalton
BG
,
Desai
AA
,
Sharp
SW
,
St Peter
SD
.
Understanding parental refusal of permission for child participation in surgical prospective trials
.
Pediatr Surg Int
.
2016
;
32
(
5
):
505
508
50
Greenberg
RG
,
Gamel
B
,
Bloom
D
, et al
.
Parents’ perceived obstacles to pediatric clinical trial participation: findings from the clinical trials transformation initiative
.
Contemp Clin Trials Commun
.
2017
;
9
:
33
39
51
Harth
SC
,
Thong
YH
.
Sociodemographic and motivational characteristics of parents who volunteer their children for clinical research: a controlled study
.
BMJ
.
1990
;
300
(
6736
):
1372
1375
52
Harth
SC
,
Johnstone
RR
,
Thong
YH
.
The psychological profile of parents who volunteer their children for clinical research: a controlled study
.
J Med Ethics
.
1992
;
18
(
2
):
86
93
53
Hayman
RM
,
Taylor
BJ
,
Peart
NS
, %
Galland
BC
,
Sayers
RM
.
Participation in research: informed consent, motivation and influence
.
J Paediatr Child Health
.
2001
;
37
(
1
):
51
54
54
Helgesson
G
,
Hansson
MG
,
Ludvigsson
J
,
Swartling
U
.
Practical matters, rather than lack of trust, motivate non- participation in a long-term cohort trial
.
Pediatr Diabetes
.
2009
;
10
(
6
):
408
412
55
Hoberman
A
,
Shaikh
N
,
Bhatnagar
S
, et al
.
Factors that influence parental decisions to participate in clinical research: consenters vs nonconsenters
.
JAMA Pediatr
.
2013
;
167
(
6
):
561
566
56
Hoehn
KS
,
Wernovsky
G
,
Rychik
J
, et al
.
What factors are important to parents making decisions about neonatal research?
Arch Dis Child Fetal Neonatal Ed
.
2005
;
90
(
3
):
F267
F269
57
Hoehn
KS
,
Nathan
A
,
White
LE
, et al
.
Parental perception of time and decision-making in neonatal research
.
J Perinatol
.
2009
;
29
(
7
):
508
511
58
Howard Sharp
KM
,
Jurbergs
N
,
Ouma
A
, et al
.
Factors associated with declining to participate in a pediatric oncology next generation sequencing study
.
JCO Precis Oncol
.
2020
;
4
:
202
211
59
Hulst
JM
,
Peters
JW
,
van den Bos
A
, et al
.
Illness severity and parental permission for clinical research in a pediatric ICU population
.
Intensive Care Med
.
2005
;
31
(
6
):
880
884
60
Ingersgaard
MV
,
Tulstrup
M
,
Schmiegelow
K
,
Larsen
HB
.
A qualitative study of decision-making on Phase III randomized clinical trial participation in paediatric oncology: adolescents’ and parents’ perspectives and preferences
.
J Adv Nurs
.
2018
;
74
(
1
):
110
118
61
Jay
F
,
Chantler
T
,
Lees
A
,
Pollard
AJ
.
Children’s participation in vaccine research: parents’ views
.
Paediatr Nurs
.
2007
;
19
(
8
):
14
18
62
Jenkins
MM
,
Reed-Gross
E
,
Rasmussen
SA
, et al
.
Maternal attitudes toward DNA collection for gene-environment studies: a qualitative research study
.
Am J Med Genet A
.
2009
;
149A
(
11
):
2378
2386
63
Jollye
S
.
An exploratory study to determine how parents decide whether to enrol their infants into neonatal clinical trials
.
J Neonatal Nurs
.
2009
;
15
(
1
):
18
24
64
Kick
K
,
Assfalg
R
,
Aydin
S
, et al
.
Recruiting young pre-symptomatic children for a clinical trial in type 1 diabetes: insights from the Fr1da insulin intervention study
.
Contemp Clin Trials Commun
.
2018
;
11
:
170
173
65
Korotchikova
I
,
Boylan
GB
,
Dempsey
EM
,
Ryan
CA
.
Presence of both parents during consent process in non-therapeutic neonatal research increases positive response
.
Acta Paediatr
.
2010
;
99
(
10
):
1484
1488
66
Kumari
S
,
Bhatia
T
,
Mishra
NN
, et al
.
Why parents consent to their children's participation in genetic research: a study of parental decision making
.
Indian J Med Ethics
.
2019
;
4
(
NS
)(
4
):
10.20529/IJME.2019.063
67
Labib
RM
,
Hassanain
O
,
Alaa
M
,
Ahmed
S
,
Abou El-Naga
S
.
Planning today for tomorrow’s research: analysis of factors influencing participation in a pediatric cancer research biorepository
.
Front Oncol
.
2018
;
7
:
324
68
Langley
JM
,
Halperin
SA
,
Mills
EL
, %
Eastwood
B
.
Parental willingness to enter a child in a controlled vaccine trial
.
Clin Invest Med
.
1998
;
21
(
1
):
12
16
69
Mason
SA
,
Allmark
PJ
.
Obtaining informed consent to neonatal randomised controlled trials: interviews with parents and clinicians in the Euricon study
.
Lancet
.
2000
;
356
(
9247
):
2045
2051
70
Mazzocco
MMM
,
Myers
GF
,
Harum
KH
,
Reiss
AL
.
Children’s participation in genetic prevalence research: influences on enrollment and reports of parent satisfaction
.
J Appl Soc Psychol
.
1999
;
29
(
11
):
2308
2327
71
Menon
K
,
Ward
RE
,
Gaboury
I
, et al
.
Factors affecting consent in pediatric critical care research
.
Intensive Care Med
.
2012
;
38
(
1
):
153
159
72
Menon
K
,
Ward
R
,
Group
CCCT
;
Canadian Critical Care Trials Group
.
A study of consent for participation in a non-therapeutic study in the pediatric intensive care population
.
J Med Ethics
.
2014
;
40
(
2
):
123
126
73
Mihrshahi
S
,
Vukasin
N
,
Forbes
S
, et al
.
Are you busy for the next 5 years? Recruitment in the Childhood Asthma Prevention Study (CAPS)
.
Respirology
.
2002
;
7
(
2
):
147
151
74
Morley
CJ
,
Lau
R
,
Davis
PG
,
Morse
C
.
What do parents think about enrolling their premature babies in several research studies?
Arch Dis Child Fetal Neonatal Ed
.
2005
;
90
(
3
):
F225
F228
75
Mwangi
R
,
Ndebele
P
,
Mongoven
A
.
Understanding, therapeutic misconceptions and perceptions, and enrollment decision-making: a pediatric preventive malaria trial in rural Tanzania
.
IRB
.
2017
;
39
(
5
):
8
18
76
Nieminen
H
,
Syrjänen
RK
,
Puumalainen
T
,
Sirén
P
,
Palmu
AA
.
Health benefit for the child and promotion of the common good were the two most important reasons for participation in the FinIP vaccine trial
.
Vaccine
.
2015
;
33
(
31
):
3695
3702
77
Norris
ML
,
Spettigue
W
,
Buchholz
A
,
Henderson
KA
,
Obeid
N
.
Factors influencing research drug trials in adolescents with anorexia nervosa
.
Eat Disord
.
2010
;
18
(
3
):
210
217
78
Pagano-Therrien
J
,
Sullivan-Bolyai
S
.
Research participation decision- making among youth and parents of youth with chronic health conditions
.
J Pediatr Health Care
.
2017
;
31
(
2
):
167
177
79
Papaz
T
,
Safi
M
,
Manickaraj
AK
, et al
.
Factors influencing participation in a population-based biorepository for childhood heart disease
.
Pediatrics
.
2012
;
130
(
5
):
e1198
e1205
80
Paquette
E
,
Shukla
A
,
Davidson
J
,
Rychlik
K
,
Davis
M
.
Burden or opportunity? Parent experiences when approached for research in a pediatric intensive care unit
.
Ethics Hum Res
.
2019
;
41
(
3
):
2
12
81
Read
K
,
Fernandez
CV
,
Gao
J
, et al
.
Decision-making by adolescents and parents of children with cancer regarding health research participation
.
Pediatrics
.
2009
;
124
(
3
):
959
965
82
Sammons
HM
,
Atkinson
M
,
Choonara
I
,
Stephenson
T
.
What motivates British parents to consent for research? A questionnaire study
.
BMC Pediatr
.
2007
;
7
:
12
83
Scollon
S
,
Bergstrom
K
,
Kerstein
RA
, et al
.
Obtaining informed consent for clinical tumor and germline exome sequencing of newly diagnosed childhood cancer patients
.
Genome Med
.
2014
;
6
(
9
):
69
84
Shilling
V
,
Young
B
.
How do parents experience being asked to enter a child in a randomised controlled trial?
BMC Med Ethics
.
2009
;
10
:
1
85
Skinner
D
,
Choudhury
S
,
Sideris
J
, et al
.
Parents’ decisions to screen newborns for FMR1 gene expansions in a pilot research project
.
Pediatrics
.
2011
;
127
(
6
):
e1455
e1463
86
Snowdon
C
,
Elbourne
D
,
Garcia
J
.
“It was a snap decision”: parental and professional perspectives on the speed of decisions about participation in perinatal randomised controlled trials
.
Soc Sci Med
.
2006
;
62
(
9
):
2279
2290
87
Sureshkumar
P
,
Caldwell
P
,
Lowe
A
,
Simpson
JM
,
Williams
G
,
Craig
JC
.
Parental consent to participation in a randomised trial in children: associated child, family, and physician factors
.
Clin Trials
.
2012
;
9
(
5
):
645
651
88
Surun
A
,
Dujaric
M
,
Aerts
I
, et al
.
Enrollment in early-phase clinical trials in pediatric oncology: the experience at Institut Curie
.
Pediatr Blood Cancer
.
2018
;
65
(
5
):
e26916
89
Tait
AR
,
Voepel-Lewis
T
,
Malviya
S
.
Participation of children in clinical research: factors that influence a parent’s decision to consent
.
Anesthesiology
.
2003
;
99
(
4
):
819
825
90
Tait
AR
,
Voepel-Lewis
T
,
Malviya
S
.
Factors that influence parents’ assessments of the risks and benefits of research involving their children
.
Pediatrics
.
2004
;
113
(
4
):
727
732
91
Tait
AR
,
Voepel-Lewis
T
,
Siewert
M
, %
Malviya
S
.
Factors that influence parents’ decisions to consent to their child’s participation in clinical anesthesia research
.
Anesth Analg
.
1998
;
86
(
1
):
50
53
92
Taylor
RG
,
Hounchell
M
,
Ho
M
,
Grupp-Phelan
J
.
Factors associated with participation in research conducted in a pediatric emergency department
.
Pediatr Emerg Care
.
2015
;
31
(
5
):
348
352
93
Thomas
M
,
Menon
K
.
Consenting to pediatric critical care research: understanding the perspective of parents
.
Dynamics
.
2013
;
24
(
3
):
18
24
94
Vecchi Brumatti
L
,
Montico
M
,
Russian
S
, et al
.
Analysis of motivations that lead women to participate (or not) in a newborn cohort study
.
BMC Pediatr
.
2013
;
13
:
53
95
Volkening
LK
,
Gaffney
KC
,
Katz
ML
,
Laffel
LM
.
Recruitment into a pediatric continuous glucose monitoring RCT
.
J Diabetes Sci Technol
.
2017
;
11
(
1
):
100
107
96
Ward
FR
.
Chaos, vulnerability and control: parental beliefs about neonatal clinical trials
.
J Perinatol
.
2009
;
29
(
2
):
156
162
97
Woodgate
RL
,
Yanofsky
RA
.
Parents' experiences in decision making with childhood cancer clinical trials
.
Cancer Nurs
.
2010
;
33
(
1
):
11
18
98
Woolfall
K
,
Shilling
V
,
Hickey
H
, et al
.
Parents’ agendas in paediatric clinical trial recruitment are different from researchers’ and often remain unvoiced: a qualitative study
.
PLoS One
.
2013
;
8
(
7
):
e67352
99
Wynn
L
,
Miller
S
,
Faughnan
L
, et al
.
Recruitment of infants with sickle cell anemia to a Phase III trial: data from the BABY HUG study
.
Contemp Clin Trials
.
2010
;
31
(
6
):
558
563
100
Bhatnagar
M
,
Sheehan
S
,
Sharma
I
, et al
.
Prospect of direct benefit in pediatric trials: practical challenges and potential solutions
.
Pediatrics
.
2021
;
147
(
5
):
e2020049602
101
Appelbaum
PS
,
Roth
LH
,
Lidz
CW
, %
Benson
P
,
Winslade
W
.
False hopes and best data: consent to research and the therapeutic misconception
.
Hastings Cent Rep
.
1987
;
17
(
2
):
20
24
102
Nathe
JM
,
Krakow
EF
.
The challenges of informed consent in high-stakes, randomized oncology trials: a systematic review
.
MDM Policy Pract
.
2019
;
4
(
1
):
2381468319840322
103
Carrera
JS
,
Brown
P
,
Brody
JG
, %
Morello-Frosch
R
.
Research altruism as motivation for participation in community-centered environmental health research
.
Soc Sci Med
.
2018
;
196
:
175
181
104
McCann
SK
,
Campbell
MK
,
Entwistle
VA
.
Reasons for participating in randomised controlled trials: conditional altruism and considerations for self
.
Trials
.
2010
;
11
:
31
105
Bradley
CK
,
Wang
TY
,
Li
S
, et al
.
Patient-reported reasons for declining or discontinuing statin therapy: insights from the PALM registry
.
J Am Heart Assoc
.
2019
;
8
(
7
):
e011765
106
Patterson
CA
,
Chavez
V
,
Mondestin
V
,
Deatrick
J
,
Li
Y
,
Barakat
LP
.
Clinical trial decision making in pediatric sickle cell disease: a qualitative study of perceived benefits and barriers to participation
.
J Pediatr Hematol Oncol
.
2015
;
37
(
6
):
415
422
107
Naidoo
N
,
Nguyen
VT
,
Ravaud
P
, et al
.
The research burden of randomized controlled trial participation: a systematic thematic synthesis of qualitative evidence
.
BMC Med
.
2020
;
18
(
1
):
6
108
Natale
P
,
Saglimbene
V
,
Ruospo
M
, et al
.
Transparency, trust and minimizing burden to increase recruitment and retention in trials: a systematic review
.
J Clin Epidemiol
.
2021
;
134
:
35
51
109
Schunk
JE
,
Jacobsen
KK
,
Stephens
D
, et al;
DKA FLUID group of the Pediatric Emergency Care Applied Research Network
.
Enroller experience and parental familiarity of disease influence participation in a pediatric trial
.
West J Emerg Med
.
2021
;
22
(
5
):
1176
1182
110
Brooks
SP
,
Bubela
T
.
Application of protection motivation theory to clinical trial enrolment for pediatric chronic conditions
.
BMC Pediatr
.
2020
;
20
(
1
):
123
111
Bailey
ZD
,
Feldman
JM
,
Bassett
MT
.
How structural racism works - racist policies as a root cause of U.S. racial health inequities
.
N Engl J Med
.
2021
;
384
(
8
):
768
773
112
Leonard
MB
,
Pursley
DM
,
Robinson
LA
,
Abman
SH
,
Davis
JM
.
The importance of trustworthiness: lessons from the COVID-19 pandemic
.
Pediatr Res
.
2022
;
91
(
3
):
482
485
113
Roper
WL
.
Science, health, and truth
.
Science
.
2022
;
377
(
6601
):
7
114
Basarab
M
,
Anderson
EE
.
Research during wartime-ethical challenges faced by oncology researchers in Ukraine
.
JAMA Oncol
.
2022
;
8
(
9
):
1254
1255
115
Bearer
CF
,
Molloy
EJ
,
Tessema
MT
, et al
.
Global climate change: the defining issue of our time for our children’s health [published online ahead of print September 8, 2022]
.
Pediatr Res
.
doi:10.1038/s41390-022-02290-7
116
Samuel
G
,
Richie
C
.
Reimagining research ethics to include environmental sustainability: a principled approach, including a case study of data-driven health research [published online ahead of print August 3, 2022]
.
J Med Ethics
.
doi: 10.1136/jme-2022-108489
117
Harris
PA
,
Taylor
R
,
Minor
BL
, et al;
REDCap Consortium
.
The REDCap consortium: building an international community of software platform partners
.
J Biomed Inform
.
2019
;
95
:
103208
118
Harris
PA
,
Taylor
R
,
Thielke
R
,
Payne
J
,
Gonzalez
N
,
Conde
JG
.
Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support
.
J Biomed Inform
.
2009
;
42
(
2
):
377
381