Parental Factors Associated With the Decision to Participate in a Neonatal Clinical Trial | Health Disparities | JAMA Network Open | JAMA Network
[Skip to Navigation]
Sign In
Table 1.  Infant Characteristics and Parental Demographic Characteristics
Infant Characteristics and Parental Demographic Characteristics
Table 2.  Parental Perception of Infant’s Condition
Parental Perception of Infant’s Condition
Table 3.  Study Comprehension
Study Comprehension
Table 4.  Parental Trust
Parental Trust
1.
Laventhal  N, Tarini  BA, Lantos  J.  Ethical issues in neonatal and pediatric clinical trials.   Pediatr Clin North Am. 2012;59(5):1205-1220. doi:10.1016/j.pcl.2012.07.007PubMedGoogle ScholarCrossref
2.
Katz  AL, Webb  SA.  Informed consent in decision-making in pediatric practice.   Pediatrics. 2016;138(2):e20161485. doi:10.1542/peds.2016-1485Google Scholar
3.
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(43):e66-e74. doi:10.1016/j.pedn.2018.07.008PubMedGoogle ScholarCrossref
4.
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. doi:10.1111/jocn.13259PubMedGoogle ScholarCrossref
5.
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. doi:10.1542/peds.2009-3353PubMedGoogle ScholarCrossref
6.
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. doi:10.1371/journal.pone.0198097PubMedGoogle Scholar
7.
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;medethics-2019-105597. doi:10.1136/medethics-2019-105597PubMedGoogle Scholar
8.
Burgess  E, Singhal  N, Amin  H, McMillan  DD, Devrome  H.  Consent for clinical research in the neonatal intensive care unit: a retrospective survey and a prospective study.   Arch Dis Child Fetal Neonatal Ed. 2003;88(4):F280-F285. doi:10.1136/fn.88.4.F280PubMedGoogle ScholarCrossref
9.
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. doi:10.1038/s41372-018-0119-6PubMedGoogle ScholarCrossref
10.
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. doi:10.1542/peds.99.1.e6PubMedGoogle Scholar
11.
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. doi:10.1542/peds.2011-2121PubMedGoogle ScholarCrossref
12.
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. doi:10.1001/jama.2015.5734PubMedGoogle ScholarCrossref
13.
Kelly  ML, Ackerman  PD, Ross  LF.  The participation of minorities in published pediatric research.   J Natl Med Assoc. 2005;97(6):777-783.PubMedGoogle Scholar
14.
Freer  Y, McIntosh  N, Teunisse  S, Anand  KJ, Boyle  EM.  More information, less understanding: a randomized study on consent issues in neonatal research.   Pediatrics. 2009;123(5):1301-1305. doi:10.1542/peds.2007-3860PubMedGoogle ScholarCrossref
15.
DeMauro  SB, Cairnie  J, D’Ilario  J, Kirpalani  H, Schmidt  B.  Honesty, trust, and respect during consent discussions in neonatal clinical trials.   Pediatrics. 2014;134(1):e1-e3. doi:10.1542/peds.2013-3720PubMedGoogle ScholarCrossref
16.
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. doi:10.1001/jamapediatrics.2013.1050PubMedGoogle ScholarCrossref
17.
Juul  SE, Comstock  BA, Heagerty  PJ,  et al.  High-dose erythropoietin for asphyxia and encephalopathy (HEAL): a randomized controlled trial—background, aims, and study protocol.   Neonatology. 2018;113(4):331-338. doi:10.1159/000486820PubMedGoogle ScholarCrossref
18.
Tagin  MA, Woolcott  CG, Vincer  MJ, Whyte  RK, Stinson  DA.  Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis.   Arch Pediatr Adolesc Med. 2012;166(6):558-566. doi:10.1001/archpediatrics.2011.1772PubMedGoogle ScholarCrossref
19.
Hall  MA, Camacho  F, Lawlor  JS, Depuy  V, Sugarman  J, Weinfurt  K.  Measuring trust in medical researchers.   Med Care. 2006;44(11):1048-1053. doi:10.1097/01.mlr.0000228023.37087.cbPubMedGoogle ScholarCrossref
20.
Dugan  E, Trachtenberg  F, Hall  MA.  Development of abbreviated measures to assess patient trust in a physician, a health insurer, and the medical profession.   BMC Health Serv Res. 2005;5:64. doi:10.1186/1472-6963-5-64PubMedGoogle ScholarCrossref
21.
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. doi:10.1542/peds.113.4.727PubMedGoogle ScholarCrossref
22.
American Association for Public Opinion Research.  Best practices for survey research.  Accessed November 2, 2020. https://www.aapor.org/Standards-Ethics/Best-Practices.aspx
23.
Sarnat  HB, Sarnat  MS.  Neonatal encephalopathy following fetal distress: a clinical and electroencephalographic study.   Arch Neurol. 1976;33(10):696-705. doi:10.1001/archneur.1976.00500100030012PubMedGoogle ScholarCrossref
24.
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. doi:10.1016/j.jbi.2019.103208PubMedGoogle Scholar
25.
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. doi:10.1016/j.jbi.2008.08.010PubMedGoogle ScholarCrossref
26.
Hoffmann  JA, Farrell  CA, Monuteaux  MC, Fleegler  EW, Lee  LK.  Association of pediatric suicide with county-level poverty in the United States, 2007-2016.   JAMA Pediatr. 2020;174(3):287-294. doi:10.1001/jamapediatrics.2019.5678PubMedGoogle ScholarCrossref
27.
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. doi:10.1016/j.cct.2008.07.006PubMedGoogle ScholarCrossref
28.
Paquette  E, Shukla  A, Duyar  S.  Social Determinants of Research Engagement and Implications for Precision Medicine: Sociodemographic Factors Associated With Differential Enrollment in a Pediatric Critical Care Biorepository. Pediatric Academic Societies; 2018.
29.
Getz  KA, Smith  ZP, Peña  Y.  Quantifying patient subpopulation disparities in new drugs and biologics approved between 2007 and 2017.   Ther Innov Regul Sci. 2020;54:1541-1550. doi:10.1007/s43441-020-00181-9PubMedGoogle ScholarCrossref
30.
Heller  C, Balls-Berry  JE, Nery  JD,  et al.  Strategies addressing barriers to clinical trial enrollment of underrepresented populations: a systematic review.   Contemp Clin Trials. 2014;39(2):169-182. doi:10.1016/j.cct.2014.08.004PubMedGoogle ScholarCrossref
31.
Braunstein  JB, Sherber  NS, Schulman  SP, Ding  EL, Powe  NR.  Race, medical researcher distrust, perceived harm, and willingness to participate in cardiovascular prevention trials.   Medicine (Baltimore). 2008;87(1):1-9. doi:10.1097/MD.0b013e3181625d78PubMedGoogle ScholarCrossref
32.
Wendler  D, Kington  R, Madans  J,  et al.  Are racial and ethnic minorities less willing to participate in health research?   PLoS Med. 2006;3(2):e19. doi:10.1371/journal.pmed.0030019PubMedGoogle Scholar
33.
Corbie-Smith  G, Thomas  SB, Williams  MV, Moody-Ayers  S.  Attitudes and beliefs of African Americans toward participation in medical research.   J Gen Intern Med. 1999;14(9):537-546. doi:10.1046/j.1525-1497.1999.07048.xPubMedGoogle ScholarCrossref
34.
Corbie-Smith  G, Thomas  SB, St George  DM.  Distrust, race, and research.   Arch Intern Med. 2002;162(21):2458-2463. doi:10.1001/archinte.162.21.2458PubMedGoogle ScholarCrossref
35.
Ross  S, Grant  A, Counsell  C, Gillespie  W, Russell  I, Prescott  R.  Barriers to participation in randomised controlled trials: a systematic review.   J Clin Epidemiol. 1999;52(12):1143-1156. doi:10.1016/S0895-4356(99)00141-9PubMedGoogle ScholarCrossref
36.
Natale  JE, Lebet  R, Joseph  JG,  et al  Racial and ethnic disparities in parental refusal of consent in a large, multisite pediatric critical care clinical trial.   J Pediatr. 2017;184:204-208.e1. doi:10.1016/j.jpeds.2017.02.006Google ScholarCrossref
37.
Liu  L, Krailo  M, Reaman  GH, Bernstein  L; Surveillance, Epidemiology and End Results Childhood Cancer Linkage Group.  Childhood cancer patients’ access to cooperative group cancer programs: a population-based study.   Cancer. 2003;97(5):1339-1345. doi:10.1002/cncr.11192PubMedGoogle ScholarCrossref
38.
Walsh  C, Ross  LF.  Are minority children under- or overrepresented in pediatric research?   Pediatrics. 2003;112(4):890-895. doi:10.1542/peds.112.4.890PubMedGoogle ScholarCrossref
39.
Schmotzer  GL.  Barriers and facilitators to participation of minorities in clinical trials.   Ethn Dis. 2012;22(2):226-230.PubMedGoogle Scholar
40.
Trent  M, Dooley  DG, Dougé  J.  The impact of racism on child and adolescent health.   Pediatrics. 2019;144(2):e20191765. doi:10.1542/peds.2019-1765Google Scholar
41.
Council on Community Pediatrics.  Poverty and child health in the United States.   Pediatrics. 2016;137(4):e20160339. doi:10.1542/peds.2016-0339Google Scholar
42.
Shiao  SY, Andrews  CM, Helmreich  RJ.  Maternal race/ethnicity and predictors of pregnancy and infant outcomes.   Biol Res Nurs. 2005;7(1):55-66. doi:10.1177/1099800405278265PubMedGoogle ScholarCrossref
43.
de Jongh  BE, Locke  R, Paul  DA, Hoffman  M.  The differential effects of maternal age, race/ethnicity, and insurance on neonatal intensive care unit admission rates.   BMC Pregnancy Childbirth. 2012;12:97. doi:10.1186/1471-2393-12-97PubMedGoogle ScholarCrossref
44.
Duncan  AF, Watterberg  KL, Nolen  TL,  et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.  Effect of ethnicity and race on cognitive and language testing at age 18-22 months in extremely preterm infants.   J Pediatr. 2012;160(6):966-71.e2. doi:10.1016/j.jpeds.2011.12.009PubMedGoogle ScholarCrossref
45.
Anderson  JG, Rogers  EE, Baer  RJ,  et al.  Racial and ethnic disparities in preterm infant mortality and severe morbidity: a population-based study.   Neonatology. 2018;113(1):44-54. doi:10.1159/000480536PubMedGoogle ScholarCrossref
46.
Wallace  ME, Mendola  P, Kim  SS,  et al.  Racial/ethnic differences in preterm perinatal outcomes.   Am J Obstet Gynecol. 2017;216(3):306.e1-306.e12. doi:10.1016/j.ajog.2016.11.1026PubMedGoogle ScholarCrossref
47.
Travers  CP, Carlo  WA, McDonald  SA,  et al; Generic Database and Follow-up Subcommittees of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.  Racial/ethnic disparities among extremely preterm infants in the United States from 2002 to 2016.   JAMA Netw Open. 2020;3(6):e206757. doi:10.1001/jamanetworkopen.2020.6757PubMedGoogle Scholar
48.
Stephens  BE, Bann  CM, Poole  WK, Vohr  BR.  Neurodevelopmental impairment: predictors of its impact on the families of extremely low birth weight infants at 18 months.   Infant Ment Health J. 2008;29(6):570-587. doi:10.1002/imhj.20196PubMedGoogle ScholarCrossref
49.
Cartwright  K, Mahoney  L, Ayers  S, Rabe  H.  Parents’ perceptions of their infants’ participation in randomized controlled trials.   J Obstet Gynecol Neonatal Nurs. 2011;40(5):555-565. doi:10.1111/j.1552-6909.2011.01276.xPubMedGoogle ScholarCrossref
50.
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. doi:10.1136/jme.2010.040220PubMedGoogle ScholarCrossref
51.
Grady  C.  Enduring and emerging challenges of informed consent.   N Engl J Med. 2015;372(9):855-862. doi:10.1056/NEJMra1411250PubMedGoogle ScholarCrossref
52.
Fryer  CS, Passmore  SR, Maietta  RC,  et al.  The symbolic value and limitations of racial concordance in minority research engagement.   Qual Health Res. 2016;26(6):830-841. doi:10.1177/1049732315575708PubMedGoogle ScholarCrossref
53.
Mindlis  I, Livert  D, Federman  AD, Wisnivesky  JP, Revenson  TA.  Racial/ethnic concordance between patients and researchers as a predictor of study attrition.   Soc Sci Med. 2020;255:113009. doi:10.1016/j.socscimed.2020.113009Google Scholar
54.
West  BT, Elliott  MR, Mneimneh  Z, Wagner  J, Peytchev  A, Trappmann  M.  An examination of an interviewer-respondent matching protocol in a longitudinal CATI study.   J Surv Stat Methodol. 2020;8(2):304-324. doi:10.1093/jssam/smy028PubMedGoogle ScholarCrossref
55.
Tooher  RL, Middleton  PF, Crowther  CA.  A thematic analysis of factors influencing recruitment to maternal and perinatal trials.   BMC Pregnancy Childbirth. 2008;8:36. doi:10.1186/1471-2393-8-36PubMedGoogle ScholarCrossref
56.
Ballard  HO, Shook  LA, Desai  NS, Anand  KJ.  Neonatal research and the validity of informed consent obtained in the perinatal period.   J Perinatol. 2004;24(7):409-415. doi:10.1038/sj.jp.7211142PubMedGoogle ScholarCrossref
57.
Guillemin  M, Barnard  E, Allen  A,  et al  Do research participants trust researchers or their institution?   J Empir Res Hum Res Ethics. 2018;13(3):285-294. doi:10.1177/1556264618763253Google ScholarCrossref
58.
Weiss  EM, Barg  FK, Cook  N, Black  E, Joffe  S.  Parental decision-making preferences in neonatal intensive care.   J Pediatr. 2016;179:36-41.e3. doi:10.1016/j.jpeds.2016.08.030PubMedGoogle ScholarCrossref
59.
Weiss  EM, Xie  D, Cook  N, Coughlin  K, Joffe  S.  Characteristics associated with preferences for parent-centered decision making in neonatal intensive care.   JAMA Pediatr. 2018;172(5):461-468. doi:10.1001/jamapediatrics.2017.5776PubMedGoogle ScholarCrossref
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    1 Comment for this article
    EXPAND ALL
    Why parents decline to participate in research
    Kenneth Harkavy, MD, MBA | Retired neonatologist
    35 years ago, I was the principle investigator for a randomized, double blind comparison of dexamethasone vs placebo in treating chronic lung disease. Even though the expected mortality of enrolled infants was 50% (a serious condition indeed), about half of the parents who were approached refused to enroll their infant. The predominant reason was that the "drug was too dangerous." Only one demanded dexamethasone for their infant, as permitted by the Institutional Review Board (but not in our original submission.) Unfortunately, we did not analyze the available parent demographics, so I cannot compare our parents to the authors'.
    />I have been involved in dozens of cases where physicians have been sued, but none involved complications of clinical research. My takeaway is that complete exposition of the risks and potential benefits is critical to true informed consent and to parent comfort. I am suspect of clinical trials where enrollment approaches 100%.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Original Investigation
    Pediatrics
    January 12, 2021

    Parental Factors Associated With the Decision to Participate in a Neonatal Clinical Trial

    Author Affiliations
    • 1Treuman Katz Center for Pediatric Bioethics, Seattle Children's Research Institute, Seattle, Washington
    • 2Department of Pediatrics, University of Washington School of Medicine, Seattle
    • 3Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York
    • 4Department of Psychology and Neuroscience, Boston College, Chestnut Hill, Massachusetts
    • 5Department of Biostatistics, University of Washington School of Public Health, Seattle
    • 6Division of Neonatology, Children’s Hospital of Orange County, Orange, California
    • 7Departments of Neurology and Pediatrics, University of California San Francisco School of Medicine, San Francisco
    • 8Department of Pediatrics, Baylor College of Medicine, San Antonio, Texas
    • 9Department of Pediatrics, Mayo Clinic, Rochester, Minnesota
    • 10Division of Neonatology, Department of Pediatrics, Children’s National Hospital, George Washington University School of Medicine and Health Sciences, Washington, DC
    • 11Department of Neonatology, Children’s Minnesota Hospital, Minneapolis
    • 12Department of Pediatrics, St Louis University School of Medicine, St Louis, Missouri
    • 13Department of Pediatrics, Washington University School of Medicine in St Louis, St Louis, Missouri
    • 14Department of Pediatrics, Cook Children’s Medical Center, Fort Worth, Texas
    • 15Division of Neonatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
    • 16Department of Pediatrics, Indiana University School of Medicine, Indianapolis
    • 17Department of Pediatrics, University of Utah School of Medicine, Salt Lake City
    • 18Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee
    • 19Department of Neurology, Children’s National Hospital, George Washington University School of Medicine and Health Sciences, Washington, DC
    • 20Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
    • 21Pediatrix Medical Group, San Antonio, Texas
    • 22Department of Neurology, Children’s National Hospital, George Washington University School of Medicine and Health Sciences, Washington, DC
    • 23Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
    JAMA Netw Open. 2021;4(1):e2032106. doi:10.1001/jamanetworkopen.2020.32106
    Key Points

    Question  How do parents with infants enrolled in a neonatal clinical trial differ from those who decline participation?

    Findings  In this survey study including 269 parent responses, participants who enrolled their infant had different demographic characteristics (lower rate of Medicaid participation, higher income, less likely to identify as Black), reported their infant’s medical condition as more serious, and reported higher trust in medical researchers compared with those who declined to enroll. There was no association between study comprehension and enrollment.

    Meaning  Differences between parents who enrolled their infant and those who declined suggest potential targets for future research aiming to better engage underrepresented groups in neonatal clinical research.

    Abstract

    Importance  It remains poorly understood how parents decide whether to enroll a child in a neonatal clinical trial. This is particularly true for parents from racial or ethnic minority populations. Understanding factors associated with enrollment decisions may improve recruitment processes for families, increase enrollment rates, and decrease disparities in research participation.

    Objective  To assess differences in parental factors between parents who enrolled their infant and those who declined enrollment for a neonatal randomized clinical trial.

    Design, Setting, and Participants  This survey study conducted from July 2017 to October 2019 in 12 US level 3 and 4 neonatal intensive care units included parents of infants who enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial or who were eligible but declined enrollment. Data were analyzed October 2019 through July 2020.

    Exposure  Parental choice of enrollment in neonatal clinical trial.

    Main Outcomes and Measures  Percentages and odds ratios (ORs) of parent participation as categorized by demographic characteristics, self-assessment of child’s medical condition, study comprehension, and trust in medical researchers. Survey questions were based on the hypothesis that parents who enrolled their infant in HEAL differ from those who declined enrollment across 4 categories: (1) infant characteristics and parental demographic characteristics, (2) perception of infant’s illness, (3) study comprehension, and (4) trust in clinicians and researchers.

    Results  Of a total 387 eligible parents, 269 (69.5%) completed the survey and were included in analysis. This included 183 of 242 (75.6%) of HEAL-enrolled and 86 of 145 (59.3%) of HEAL-declined parents. Parents who enrolled their infant had lower rates of Medicaid participation (74 [41.1%] vs 47 [55.3%]; P = .04) and higher rates of annual income greater than $55 000 (94 [52.8%] vs 30 [37.5%]; P = .03) compared with those who declined. Black parents had lower enrollment rates compared with White parents (OR, 0.35; 95% CI, 0.17-0.73). Parents who reported their infant’s medical condition as more serious had higher enrollment rates (OR, 5.7; 95% CI, 2.0-16.3). Parents who enrolled their infant reported higher trust in medical researchers compared with parents who declined (mean [SD] difference, 5.3 [0.3-10.3]). There was no association between study comprehension and enrollment.

    Conclusions and Relevance  In this study, the following factors were associated with neonatal clinical trial enrollment: demographic characteristics (ie, race/ethnicity, Medicaid status, and reported income), perception of illness, and trust in medical researchers. Future work to confirm these findings and explore the reasons behind them may lead to strategies for better engaging underrepresented groups in neonatal clinical research to reduce enrollment disparities.

    Introduction

    Clinical trials are essential to advance neonatal care, but recruitment for them can be ethically complex. Because infants cannot provide consent for themselves,1 parents or guardians are asked for their permission.2 Recruitment can also be challenging because parents are under significant strain, and their vulnerable, sick infants often must be enrolled quickly if they are to participate.3-6

    There are limited data to explain how parents decide whether to participate in neonatal clinical trials. Previous research has struggled to include the views of those who decline neonatal research7,8 with only a few exceptions.9,10 Low enrollment rates within neonatal clinical trials diminish the quality of data collected and limit the generalizability of results.11 Racial and ethnic disparities exist in neonatal research enrollment, but we do not fully understand which groups are overrepresented or underrepresented.12,13 Other parental factors that are potentially important in enrollment decisions include study comprehension9,14 and medical trust.7,15,16 Understanding these factors may enable researchers to improve recruitment processes, optimize enrollment rates, and decrease disparities in research participation.

    The High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial was a multisite randomized clinical trial (RCT) assessing erythropoietin as a neuroprotectant for infants with moderate to severe neonatal encephalopathy.17 Infants eligible for HEAL had an estimated gestational age greater than 36 weeks with moderate or severe neonatal encephalopathy undergoing therapeutic hypothermia. This population has a high risk of death in the neonatal period (approximately 28%) and of neurodevelopmental impairment among survivors (approximately 20%).18 We sought to identify differences between parents who enrolled and those who declined enrollment. We evaluated 4 categories: (1) infant characteristics and parental demographic characteristics, (2) parental perception of infant’s illness, (3) parental study comprehension, and (4) parental trust in clinicians and researchers.

    Methods
    Survey Development

    We administered a survey to parents of infants approached for enrollment in the HEAL trial. The survey instrument was developed using: (1) validated question scales where available,19,20 (2) questions from previous surveys on parental participation in pediatric research,9,16,21 and (3) questions created after input from experts in survey design, medical decision-making, clinical trials, neonatology, and research ethics. We received feedback from the neonatal intensive care unit (NICU) parent advisory council at the University of Washington. This study followed American Association for Public Opinion Research (AAPOR) reporting guideline for best practices including survey design (ie, utilizing conceptual modeling, questionnaire pretesting), standardized administration, and clear reporting.22 Institutional review board (IRB) approval was received at each of the 12 participating sites and at subsites where applicable. Each IRB made the determination whether permission to participate was obtained by written informed consent, by oral assent, or if the survey was granted a waiver.

    Infant characteristics included for analysis were birth weight, estimated gestational age at birth, whether inborn (recruited for HEAL at birth hospital) or outborn (transferred from another hospital), Medicaid status, severity of neonatal encephalopathy based on Sarnat exam prior to 6 hours of age,23 and day of life of survey. Parental demographic variables included gender, education, household income, prior experience with medical research, other children, race and ethnicity, and language spoken at home. Infant characteristics were obtained from the medical record; all other reported data were obtained via survey.

    Parental perception of their infant’s condition was assessed using 7 novel questions. Responses were recorded on a 5-point Likert scale from 1 (“not at all”) to 5 (“very much”). Higher scores indicated increased concern of illness severity. Parental comprehension of the HEAL trial was assessed by 10 novel true-false questions. Questions addressed details of the HEAL trial, voluntariness of participation, and follow-up requirements. Trust was measured using 3 preexisting validated scales with minor adjustments in wording to fit the patient population: Hall’s 4-item trust in medical research scale19 and Dugan’s 5-item trust in the medical profession and 5-item trust in a physician scales.20

    Surveys were refined using cognitive interviews with 10 parents of NICU patients by a single trained interviewer (E.M.W.) to assess comprehension and interpretation. The final survey was translated into Spanish by a certified medical translation service. Study data were collected and managed using REDCap electronic data capture tools (REDCap Consortium) hosted at the University of Washington.24,25 Both English and Spanish versions of the survey were inputted into the REDCap platform.

    Recruitment

    Surveys were fielded at 12 of 17 HEAL sites from July 28, 2017, to October 30, 2019. All parents approached for HEAL trial enrollment were eligible. Parents of infants who were ineligible and those who were eligible but not enrolled for other reasons (eg, unavailability of study drug or research coordinator) were excluded. Given the acute stressors of neonatal encephalopathy diagnosis and deciding on enrollment in a clinical trial, eligibility did not begin until the infant’s fifth day of life. Each family could choose 1 parent to participate until their infant’s hospital discharge or death.

    Interviewers read questions aloud to parents and entered responses directly into REDCap to minimize transcription errors. Interviewers were excluded from surveying families they had approached for HEAL RCT participation. Preference was given for in-person administration, but the survey was administered over phone when necessary. After survey completion, parents were offered a gift card or small toy based on local IRB preference. A Spanish language version of the survey was offered to families using a Spanish language speaking interviewer or via interpreter, if necessary.

    Variables

    We combined self-reported race and ethnicity into 4 mutually exclusive categories: Hispanic, non-Hispanic Black (hereafter “Black”), non-Hispanic White (hereafter “White”), and non-Hispanic other (ie, Asian, American Indian or Alaska Native, Native Hawaiian or other Pacific Islander), as has been done previously and is consistent with the US Census Bureau approach.26

    To simplify analysis, we dichotomized the 5-point responses for each question set (eg, for parental perception of infant’s illness, 1-3 was categorized as “less concerned” and 4-5 as “concerned”).

    Statistical Analysis

    Standard descriptive statistics were applied to our factors of interest. We fit several multivariate logistic regression models to investigate the associations of parental factors (ie, demographic characteristics, perception of infant’s illness, study comprehension, and trust scales) with enrollment decision. We examined the association between each parental factor and enrollment decision by comparing odds ratios (ORs) between groups. In each model, we adjusted for race, Medicaid status, and household income to eliminate potential confounding. We report estimates of ORs along with 95% confidence intervals constructed using robust standard errors.

    Data were analyzed October 2019 through July 2020. All P values are 2-sided and not adjusted for multiple comparisons; an association was considered significant if P < .05. We performed a planned secondary analysis to evaluate the interaction between race/ethnicity and each of the parental factors separately to assess whether each factor was differentially associated with enrollment by race. All analyses were conducted using the R statistical package version 3.6.1 (R Project for Statistical Computing).

    Results
    Infant Characteristics and Parental Demographics

    Analysis included 269 of 387 (69.5%) eligible parents across 12 US sites who completed the survey. Of these, 177 (67.0%) participants were mothers, 121 (45.7%) were receiving Medicaid, and 124 (48.1%) reported income $55 000 or greater. Self-reported race/ethnicity of participants was 148 (55.0%) White, 61 (22.9%) Hispanic, and 39 (14.5%) Black (Table 1). Surveys captured 183 of 242 (75.6%) HEAL-enrolled and 86 of 145 (59.3%) HEAL-declined parents. The 86 parents who declined HEAL and participated in our survey included 1 who did not respond after approach by study staff, 16 who did not wish to talk to study staff, and 69 who declined trial participation after discussion with study staff. There were no significant differences in infant characteristics between the 2 groups (Table 1). Parents of infants who were not receiving Medicaid or who reported higher income were significantly more likely to enroll their children in the study (eg, Medicaid recipients vs annual income ≥$55 000 enrollment: 74 (41.1%) participants vs 94 (52.8%) participants; Table 1). Enrollment status was significantly different between race/ethnicity groups, with lowest relative enrollment among Black parents compared with White parents (OR, 0.35; 95% CI, 0.17-0.73). In a planned secondary analysis, none of the interactions between race/ethnicity and other parental factors were significant.

    Perception of Infant’s Illness

    We observed significant differences in parental perception of their infant’s condition. Parents who enrolled their infant in HEAL reported their infant’s medical condition to be more serious compared with parents who declined for 4 of 7 questions (eg, enrollment and agreement with the statement, “I very much or moderately thought my infant’s illness was a serious medical condition,” ≥4 on a 5-point scale: OR, 5.7; 95% CI, 2.0-16.3) (Table 2). After adjusting for race, Medicaid status, and household income, the association between parental perception of illness and enrollment remained significant. The association between parental perception of their infant’s illness and study enrollment did not differ by race, reported income, or Medicaid status.

    Because we found this association between parental perception of illness and enrollment, we looked for an association between parental perception of illness and Sarnat classification. The percentage of parents who responded that they “very much” or “moderately” thought their infant was sick was higher for parents of infants with severe Sarnat stage (41 of 46 [89%]) compared with parents of infants with moderate Sarnat stage (166 of 221 [75%]) (OR, 3.2; 95% CI, 1.2-11.0) (eTable in the Supplement). For each of the other 6 questions related to parental perception of their infant’s illness, the association with Sarnat classification was not significant.

    We asked a single question on parental self-assessment of understanding of their infant’s illness: “How much did you understand your infant’s illness?” Self-assessment of understanding of their infant’s illness did not differ between parents who enrolled in HEAL and those who declined. Roughly half of respondents self-reported a low level of understanding of their infant’s condition.

    Comprehension of HEAL Study

    Parental comprehension was high, with a mean (SD) of 8.9 (1.2) out of 10 questions answered correctly; the median (interquartile range) number of correct answers was 9.0 (8.0-10.0). Total correct answers did not differ significantly between those who did and did not enroll in HEAL (Table 3).

    Trust of Clinicians and Researchers

    Enrolled parents reported significantly higher levels of trust in medical researchers compared with parents who declined (mean [SD] score, 71.7% [17.2%] vs 64.8% [20.8%]) (Table 4). There was no difference in reported trust in the medical profession (61.7% [13.7%] vs 60.1% [13.0%]) or trust in the infant’s neonatologist between groups (70.3% [11.6%] vs 70.1% [11.1%]). After adjusting for race, Medicaid status and household income, the association of trust in medical researchers with enrollment decision remained significant (mean difference, 5.3%; 95% CI, 0.3%-10.3%). The association between trust and study enrollment did not differ by race, reported income, or Medicaid status.

    Discussion

    This study lends insight into factors associated with parental decision-making that can inform future strategies to improve enrollment for neonatal RCTs. First, rates of participation differed by race and income. Second, although Sarnat classification of objective illness severity did not differ between groups, parents who declined HEAL enrollment felt their infant was less ill than those who enrolled. Third, there was no association between study comprehension and enrollment. Fourth, a specific decreased trust in medical researchers may be driving lower enrollment rates, rather than general medical distrust.

    Infant Characteristics and Parental Demographic Characteristics

    We found lower enrollment among parents on Medicaid and with lower incomes. These findings are consistent with previously observed recruitment disparities in adults from underserved populations.27 In pediatrics, the relationship between socioeconomic status (SES) and research enrollment is poorly described, and with conflicting results.10,16,28 We also found that Black parents enrolled their infants in HEAL less frequently than White parents. The association between the parental factors we studied (perception of their infant’s illness, medical trust, and study comprehension) and HEAL enrollment did not differ by race, Medicaid status, or reported income.

    Black participants are the most underrepresented within US research in adults.29,30 While some have emphasized historical abuse and persistent distrust in medical research,31 others have emphasized limited access to clinical trials.32 Other factors that may contribute to disparities in research participation include implicit and explicit biases of research team members and financial or transportation barriers.33-35 Establishing community partnerships and building relationships with underrepresented populations are also important.27 Enrollment of racial and ethnic minorities in pediatric clinical research, though less well-studied, is lower than for White children including within critical care,28,36 oncology,37 and neonatology.11,12 Conversely, assessments of published articles in 3 general pediatric journals found overrepresentation of Black participants and underrepresentation of Hispanic participants when comparing with US Census Bureau data.13,38 The lack of clarity highlights the need for more work in this area.

    Contributors to disparities in clinical trial participation are complex and will require multilevel solutions.39 Racism and poverty are both social determinants of health that profoundly impact pediatric health outcomes.40,41 Neonatal outcomes in the US are worse for Black infants42-47 and for infants from families with low SES.48 Populations that are systematically underrepresented in neonatal research fail to benefit from research, which could exacerbate existing disparities in neonatal clinical outcomes.45 Future work must study these disparities and other potential drivers of differences in enrollment to improve representation within neonatal research and address persistent injustices.

    Parental Perception of Infant’s Condition

    We found that parents who enrolled their infants in HEAL reported perceiving their infant’s medical condition to be more serious compared with those who declined HEAL enrollment. Although we do not have additional data describing illness severity, the Sarnat scores23 in the 2 groups were equivalent. This suggests that the groups were comprised of infants with similar illness severity at time of HEAL enrollment. Thus, the most likely reason for this finding is that parents were more likely to decline HEAL because of an incorrect assessment that their child was less sick than they were. Believing an infant to be gravely ill might make a parent more willing to enroll in research.49,50 Importantly, all infants eligible for HEAL were at high risk for neurodevelopmental impairment.

    Future work should evaluate how illness perception may influence enrollment decisions. If parental perception of illness severity mediates the decision to enroll, then an intervention that improves parental understanding of their infant’s medical condition may both improve the quality of clinical decision-making and increase enrollment for neonatal clinical trials.

    Future work should evaluate the contributors to parental perception of their infant’s illness. Such work must gather more granular clinical data to better understand how parents develop their perception of their infant’s illness. Considering the HEAL eligible population, for example, it would be useful to know short-term (eg, intubation or pressor requirement), medium-term (eg, MRI findings, neurological exam, and feeding support requirements at discharge), and long-term (eg, 2-year neurodevelopmental assessment) outcomes, in addition to how perception of illness may change over time.

    Study Comprehension

    Although study comprehension is an enduring challenge for clinical trial enrollment51 and has been posited as a reason for lower enrollment of racial and ethnic minorities and individuals of lower SES,9,14 we did not find differences in study comprehension between parents who enrolled and those who did not enroll in neonatal research. Researchers were able to educate parents to achieve high levels of comprehension about the HEAL study. This suggests that study comprehension was not a major problem among parents approached for the HEAL trial. Future work must assess the role of study comprehension for enrollment decisions in other neonatal clinical trials.

    Trust

    We found higher levels of trust in medical researchers among enrolled parents compared with parents who declined, but no difference in trust in clinicians on 2 trust scales. The higher trust in medical researchers among enrolled parents is consistent with reflections of experienced NICU clinical researchers15 as well as interview7 and survey16 studies of parents considering research participation.

    Our findings are novel because they add nuance to the existing literature on the relationship between trust and parental decision to enroll in pediatric research.7,16 Our findings suggest it is not simply global trust in medicine, but a particular kind of trust—that of medical researchers—which may mediate enrollment decisions. There has been growing attention to race/ethnicity concordance between participants and research staff as part of research engagement with underrepresented populations.52 The relationship between concordance, trust in medical researchers, and research participation remains poorly described. For example, a 2020 study53 found greater clinical trial attrition among race/ethnicity concordant dyads compared with discordant dyads. Such findings, paired with the pragmatic challenges of implementation,54 highlight the complexity of these issues. Future work should assess whether interventions to build trust in researchers and other study personnel, whether at the community or individual level, can increase enrollment for neonatal clinical trials.

    Limitations

    This study had several limitations. Although we succeeded in including a large number who declined participation in HEAL, families who declined survey participation might differ from those who participated. Characteristics of the HEAL eligible population and of the HEAL study may have influenced the enrollment decision in unknown ways that may impact generalizability. We did not assess recruitment practices (eg, tracking of potential participants, research team composition, method of contact with families), which varied across sites and may influence enrollment.55 Our eligibility window (infant’s fifth day of life through hospital discharge) may have affected recall.56 Although we asked parents to answer questions thinking back to the time of enrollment, responses may have been influenced by subsequent events. We did not assess trust in research institutions, which may be important and different than trust in medical researchers.57 We did not evaluate race/ethnicity concordance between parents and research staff. Our questions about illness perception, based on previous work suggesting parental perception of illness severity and urgency influences clinical decision-making in the NICU,58,59 have not been validated. Our study comprehension questions may not have been at the right level of difficulty to capture the full range of parental understanding.

    Conclusions

    This study identified the following factors associated with whether a parent enrolled their child in a neonatal clinical trial: demographic characteristics (ie, reported parental race/ethnicity, infant’s Medicaid status, and reported parental income), perception of infant’s illness severity, and trust in medical researchers. We found lower rates of enrollment among Black parents compared with White parents, parents with lower income compared with those with higher income, parents who perceived their infant as less severely ill, and parents with lower trust in medical researchers. Future work should seek to confirm our findings in other neonatal clinical trials and explore the reasons behind them. In particular, greater understanding of how parents evaluate their infants’ clinical condition and how this influences clinical trial enrollment is critically important. Future work should also assess strategies for better engaging underrepresented groups in neonatal clinical research and reducing enrollment disparities. Understanding the differences between parents who enroll and those who do not enroll their infant in neonatal clinical trials will help identify interventions to improve enrollment and ensure that the results and benefits of research are more accurate and equitable.

    Back to top
    Article Information

    Accepted for Publication: November 9, 2020.

    Published: January 12, 2021. doi:10.1001/jamanetworkopen.2020.32106

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Weiss EM et al. JAMA Network Open.

    Corresponding Author: Elliott M. Weiss, MD, MSME, Division of Neonatology, University of Washington, Treuman Katz Center for Pediatric Bioethics, Seattle Children’s Hospital & Research Institute, 4800 Sand Point Way NE, M/S FA.2.113 Neonatology, Seattle, WA 98105 (emweiss@uw.edu).

    Author Contributions: Dr Weiss had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Weiss, Guttmann, A. Shah, Juul, Ahmad, Riley, Torr, Dudley, Wilfond, S. Shah.

    Acquisition, analysis, or interpretation of data: Weiss, Olszewski, Guttmann, Magnus, Li, Wu, Ahmad, Bendel-Stenzel, Isaza, Lampland, Mathur, Rao, Riley, Russell, Salih, Torr, Weitkamp, Anani, Chang, Flibotte, Havrilla, Kathen, O’Kane, Perez, Stanley, S. Shah.

    Drafting of the manuscript: Weiss, Olszewski, Li, Weitkamp, Perez.

    Critical revision of the manuscript for important intellectual content: Weiss, Olszewski, Guttmann, Magnus, A. Shah, Juul, Wu, Ahmad, Bendel-Stenzel, Isaza, Lampland, Mathur, Rao, Riley, Russell, Salih, Torr, Weitkamp, Anani, Chang, Dudley, Flibotte, Havrilla, Kathen, O’Kane, Perez, Stanley, Wilfond, S. Shah.

    Statistical analysis: Weiss, Magnus, Li.

    Obtained funding: Weiss, Juul.

    Administrative, technical, or material support: Weiss, Guttmann, Ahmad, Bendel-Stenzel, Isaza, Riley, Russell, Salih, Torr, Dudley, Havrilla, O'Kane, Perez.

    Supervision: Weiss, Wu, Ahmad, Bendel-Stenzel, Torr, Wilfond, S. Shah.

    Conflict of Interest Disclosures: Dr Weitkamp reports receiving fees in his role as a consultant for Roche Diagnostics Corporation to help with development of a neonatal sepsis marker. Dr Juul reported receiving grants from the National Institutes of Health (NIH), grants from Cerebral Palsy Alliance, and grants from Gates Foundation during the conduct of the study. Dr Weitkamp reported receiving grants from NIH during the conduct of the study; personal fees from Roche Diagnostics Consultant, grants from NIH as coinvestigator or site principle investigator (PI), nonfinancial support from Fresenius Kabi as site PI, nonfinancial support from ONY Biotech as site PI, and grants from Gates Foundation as coinvestigator outside the submitted work. Dr Flibotte reported receiving personal fees from Cipriani and Werner, PC, personal fees from Hunton, Andrews, Kurth LLC, personal fees from St Peter’s University Hospital, personal fees from White and Williams, LLP, and personal fees from Main Line Health outside the submitted work. Dr S. Shah reported receiving grants from Seattle Children’s Hospital Center for Clinical & Translational Research Clinical Research Scholars Program, grants from Children’s Minnesota Research Grant Program, and grants from University of Washington Neonatal Bioresearch Fund during the conduct of the study. No other disclosures were reported.

    Funding/Support: The study was funded by Seattle Children’s Hospital Center for Clinical & Translational Research Clinical Research Scholars Program with additional support from Children’s Minnesota Research Grant Program and University of Washington Neonatal Bioresearch Fund.

    Role of the Funder/Sponsor: The funders had no role in the 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.

    Additional Contributions: We thank the parents who participated in our survey study, both those who enrolled and those who declined participation in HEAL. We thank the research team for the parent HEAL trial and National Institute for Neurological Disorders and Stroke for funding the parent HEAL trial. We thank the members of the University of Washington NICU Family Advisory Council. We thank Tira Oskoui, BS, Children’s National Hospital, and Kaeley Stout, BA, Seattle Children’s Research Institute, for literature review assistance. We thank Deepthi Nair, MS, formerly with Seattle Children’s Hospital and now with Avalyn Pharma, for assistance with REDCap creation. We would like to acknowledge assistance with survey administration and other administrative support from: Washington University School of Medicine, Antony Barton; Children’s National Hospital, Andrea DeMarsh, BA; University of Washington School of Medicine, Isabella Esposito, BS; Seattle Children’s Hospital, Sheila Ganti, PhD; University of California San Francisco, Amy M. Goodman, PhD, Fernando Gonzalez, MD, and Kelleen Nelson, BS; Children’s Minnesota, Alissa Jorgenson, BA, and Catherine Worwa, BS; Cincinnati Children’s and University of Cincinnati College of Medicine, Brenda B. Poindexter, MD; Vanderbilt University Medical Center, Theresa J. Rogers, ADN; Pediatrix Medical Group San Antonio Texas, Vivek Vijayamadhavan, MD; Children’s Hospital of Philadelphia, Danielle D. Weinberg, MPH. None of the above nonauthor contributors were provided monetary compensation.

    Additional Information: Tablets were loaned by Seattle Children’s Hospital’s Digital Health and Information Technology Departments and the Center for Child Health, Behavior and Development.

    References
    1.
    Laventhal  N, Tarini  BA, Lantos  J.  Ethical issues in neonatal and pediatric clinical trials.   Pediatr Clin North Am. 2012;59(5):1205-1220. doi:10.1016/j.pcl.2012.07.007PubMedGoogle ScholarCrossref
    2.
    Katz  AL, Webb  SA.  Informed consent in decision-making in pediatric practice.   Pediatrics. 2016;138(2):e20161485. doi:10.1542/peds.2016-1485Google Scholar
    3.
    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(43):e66-e74. doi:10.1016/j.pedn.2018.07.008PubMedGoogle ScholarCrossref
    4.
    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. doi:10.1111/jocn.13259PubMedGoogle ScholarCrossref
    5.
    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. doi:10.1542/peds.2009-3353PubMedGoogle ScholarCrossref
    6.
    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. doi:10.1371/journal.pone.0198097PubMedGoogle Scholar
    7.
    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;medethics-2019-105597. doi:10.1136/medethics-2019-105597PubMedGoogle Scholar
    8.
    Burgess  E, Singhal  N, Amin  H, McMillan  DD, Devrome  H.  Consent for clinical research in the neonatal intensive care unit: a retrospective survey and a prospective study.   Arch Dis Child Fetal Neonatal Ed. 2003;88(4):F280-F285. doi:10.1136/fn.88.4.F280PubMedGoogle ScholarCrossref
    9.
    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. doi:10.1038/s41372-018-0119-6PubMedGoogle ScholarCrossref
    10.
    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. doi:10.1542/peds.99.1.e6PubMedGoogle Scholar
    11.
    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. doi:10.1542/peds.2011-2121PubMedGoogle ScholarCrossref
    12.
    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. doi:10.1001/jama.2015.5734PubMedGoogle ScholarCrossref
    13.
    Kelly  ML, Ackerman  PD, Ross  LF.  The participation of minorities in published pediatric research.   J Natl Med Assoc. 2005;97(6):777-783.PubMedGoogle Scholar
    14.
    Freer  Y, McIntosh  N, Teunisse  S, Anand  KJ, Boyle  EM.  More information, less understanding: a randomized study on consent issues in neonatal research.   Pediatrics. 2009;123(5):1301-1305. doi:10.1542/peds.2007-3860PubMedGoogle ScholarCrossref
    15.
    DeMauro  SB, Cairnie  J, D’Ilario  J, Kirpalani  H, Schmidt  B.  Honesty, trust, and respect during consent discussions in neonatal clinical trials.   Pediatrics. 2014;134(1):e1-e3. doi:10.1542/peds.2013-3720PubMedGoogle ScholarCrossref
    16.
    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. doi:10.1001/jamapediatrics.2013.1050PubMedGoogle ScholarCrossref
    17.
    Juul  SE, Comstock  BA, Heagerty  PJ,  et al.  High-dose erythropoietin for asphyxia and encephalopathy (HEAL): a randomized controlled trial—background, aims, and study protocol.   Neonatology. 2018;113(4):331-338. doi:10.1159/000486820PubMedGoogle ScholarCrossref
    18.
    Tagin  MA, Woolcott  CG, Vincer  MJ, Whyte  RK, Stinson  DA.  Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis.   Arch Pediatr Adolesc Med. 2012;166(6):558-566. doi:10.1001/archpediatrics.2011.1772PubMedGoogle ScholarCrossref
    19.
    Hall  MA, Camacho  F, Lawlor  JS, Depuy  V, Sugarman  J, Weinfurt  K.  Measuring trust in medical researchers.   Med Care. 2006;44(11):1048-1053. doi:10.1097/01.mlr.0000228023.37087.cbPubMedGoogle ScholarCrossref
    20.
    Dugan  E, Trachtenberg  F, Hall  MA.  Development of abbreviated measures to assess patient trust in a physician, a health insurer, and the medical profession.   BMC Health Serv Res. 2005;5:64. doi:10.1186/1472-6963-5-64PubMedGoogle ScholarCrossref
    21.
    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. doi:10.1542/peds.113.4.727PubMedGoogle ScholarCrossref
    22.
    American Association for Public Opinion Research.  Best practices for survey research.  Accessed November 2, 2020. https://www.aapor.org/Standards-Ethics/Best-Practices.aspx
    23.
    Sarnat  HB, Sarnat  MS.  Neonatal encephalopathy following fetal distress: a clinical and electroencephalographic study.   Arch Neurol. 1976;33(10):696-705. doi:10.1001/archneur.1976.00500100030012PubMedGoogle ScholarCrossref
    24.
    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. doi:10.1016/j.jbi.2019.103208PubMedGoogle Scholar
    25.
    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. doi:10.1016/j.jbi.2008.08.010PubMedGoogle ScholarCrossref
    26.
    Hoffmann  JA, Farrell  CA, Monuteaux  MC, Fleegler  EW, Lee  LK.  Association of pediatric suicide with county-level poverty in the United States, 2007-2016.   JAMA Pediatr. 2020;174(3):287-294. doi:10.1001/jamapediatrics.2019.5678PubMedGoogle ScholarCrossref
    27.
    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. doi:10.1016/j.cct.2008.07.006PubMedGoogle ScholarCrossref
    28.
    Paquette  E, Shukla  A, Duyar  S.  Social Determinants of Research Engagement and Implications for Precision Medicine: Sociodemographic Factors Associated With Differential Enrollment in a Pediatric Critical Care Biorepository. Pediatric Academic Societies; 2018.
    29.
    Getz  KA, Smith  ZP, Peña  Y.  Quantifying patient subpopulation disparities in new drugs and biologics approved between 2007 and 2017.   Ther Innov Regul Sci. 2020;54:1541-1550. doi:10.1007/s43441-020-00181-9PubMedGoogle ScholarCrossref
    30.
    Heller  C, Balls-Berry  JE, Nery  JD,  et al.  Strategies addressing barriers to clinical trial enrollment of underrepresented populations: a systematic review.   Contemp Clin Trials. 2014;39(2):169-182. doi:10.1016/j.cct.2014.08.004PubMedGoogle ScholarCrossref
    31.
    Braunstein  JB, Sherber  NS, Schulman  SP, Ding  EL, Powe  NR.  Race, medical researcher distrust, perceived harm, and willingness to participate in cardiovascular prevention trials.   Medicine (Baltimore). 2008;87(1):1-9. doi:10.1097/MD.0b013e3181625d78PubMedGoogle ScholarCrossref
    32.
    Wendler  D, Kington  R, Madans  J,  et al.  Are racial and ethnic minorities less willing to participate in health research?   PLoS Med. 2006;3(2):e19. doi:10.1371/journal.pmed.0030019PubMedGoogle Scholar
    33.
    Corbie-Smith  G, Thomas  SB, Williams  MV, Moody-Ayers  S.  Attitudes and beliefs of African Americans toward participation in medical research.   J Gen Intern Med. 1999;14(9):537-546. doi:10.1046/j.1525-1497.1999.07048.xPubMedGoogle ScholarCrossref
    34.
    Corbie-Smith  G, Thomas  SB, St George  DM.  Distrust, race, and research.   Arch Intern Med. 2002;162(21):2458-2463. doi:10.1001/archinte.162.21.2458PubMedGoogle ScholarCrossref
    35.
    Ross  S, Grant  A, Counsell  C, Gillespie  W, Russell  I, Prescott  R.  Barriers to participation in randomised controlled trials: a systematic review.   J Clin Epidemiol. 1999;52(12):1143-1156. doi:10.1016/S0895-4356(99)00141-9PubMedGoogle ScholarCrossref
    36.
    Natale  JE, Lebet  R, Joseph  JG,  et al  Racial and ethnic disparities in parental refusal of consent in a large, multisite pediatric critical care clinical trial.   J Pediatr. 2017;184:204-208.e1. doi:10.1016/j.jpeds.2017.02.006Google ScholarCrossref
    37.
    Liu  L, Krailo  M, Reaman  GH, Bernstein  L; Surveillance, Epidemiology and End Results Childhood Cancer Linkage Group.  Childhood cancer patients’ access to cooperative group cancer programs: a population-based study.   Cancer. 2003;97(5):1339-1345. doi:10.1002/cncr.11192PubMedGoogle ScholarCrossref
    38.
    Walsh  C, Ross  LF.  Are minority children under- or overrepresented in pediatric research?   Pediatrics. 2003;112(4):890-895. doi:10.1542/peds.112.4.890PubMedGoogle ScholarCrossref
    39.
    Schmotzer  GL.  Barriers and facilitators to participation of minorities in clinical trials.   Ethn Dis. 2012;22(2):226-230.PubMedGoogle Scholar
    40.
    Trent  M, Dooley  DG, Dougé  J.  The impact of racism on child and adolescent health.   Pediatrics. 2019;144(2):e20191765. doi:10.1542/peds.2019-1765Google Scholar
    41.
    Council on Community Pediatrics.  Poverty and child health in the United States.   Pediatrics. 2016;137(4):e20160339. doi:10.1542/peds.2016-0339Google Scholar
    42.
    Shiao  SY, Andrews  CM, Helmreich  RJ.  Maternal race/ethnicity and predictors of pregnancy and infant outcomes.   Biol Res Nurs. 2005;7(1):55-66. doi:10.1177/1099800405278265PubMedGoogle ScholarCrossref
    43.
    de Jongh  BE, Locke  R, Paul  DA, Hoffman  M.  The differential effects of maternal age, race/ethnicity, and insurance on neonatal intensive care unit admission rates.   BMC Pregnancy Childbirth. 2012;12:97. doi:10.1186/1471-2393-12-97PubMedGoogle ScholarCrossref
    44.
    Duncan  AF, Watterberg  KL, Nolen  TL,  et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.  Effect of ethnicity and race on cognitive and language testing at age 18-22 months in extremely preterm infants.   J Pediatr. 2012;160(6):966-71.e2. doi:10.1016/j.jpeds.2011.12.009PubMedGoogle ScholarCrossref
    45.
    Anderson  JG, Rogers  EE, Baer  RJ,  et al.  Racial and ethnic disparities in preterm infant mortality and severe morbidity: a population-based study.   Neonatology. 2018;113(1):44-54. doi:10.1159/000480536PubMedGoogle ScholarCrossref
    46.
    Wallace  ME, Mendola  P, Kim  SS,  et al.  Racial/ethnic differences in preterm perinatal outcomes.   Am J Obstet Gynecol. 2017;216(3):306.e1-306.e12. doi:10.1016/j.ajog.2016.11.1026PubMedGoogle ScholarCrossref
    47.
    Travers  CP, Carlo  WA, McDonald  SA,  et al; Generic Database and Follow-up Subcommittees of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.  Racial/ethnic disparities among extremely preterm infants in the United States from 2002 to 2016.   JAMA Netw Open. 2020;3(6):e206757. doi:10.1001/jamanetworkopen.2020.6757PubMedGoogle Scholar
    48.
    Stephens  BE, Bann  CM, Poole  WK, Vohr  BR.  Neurodevelopmental impairment: predictors of its impact on the families of extremely low birth weight infants at 18 months.   Infant Ment Health J. 2008;29(6):570-587. doi:10.1002/imhj.20196PubMedGoogle ScholarCrossref
    49.
    Cartwright  K, Mahoney  L, Ayers  S, Rabe  H.  Parents’ perceptions of their infants’ participation in randomized controlled trials.   J Obstet Gynecol Neonatal Nurs. 2011;40(5):555-565. doi:10.1111/j.1552-6909.2011.01276.xPubMedGoogle ScholarCrossref
    50.
    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. doi:10.1136/jme.2010.040220PubMedGoogle ScholarCrossref
    51.
    Grady  C.  Enduring and emerging challenges of informed consent.   N Engl J Med. 2015;372(9):855-862. doi:10.1056/NEJMra1411250PubMedGoogle ScholarCrossref
    52.
    Fryer  CS, Passmore  SR, Maietta  RC,  et al.  The symbolic value and limitations of racial concordance in minority research engagement.   Qual Health Res. 2016;26(6):830-841. doi:10.1177/1049732315575708PubMedGoogle ScholarCrossref
    53.
    Mindlis  I, Livert  D, Federman  AD, Wisnivesky  JP, Revenson  TA.  Racial/ethnic concordance between patients and researchers as a predictor of study attrition.   Soc Sci Med. 2020;255:113009. doi:10.1016/j.socscimed.2020.113009Google Scholar
    54.
    West  BT, Elliott  MR, Mneimneh  Z, Wagner  J, Peytchev  A, Trappmann  M.  An examination of an interviewer-respondent matching protocol in a longitudinal CATI study.   J Surv Stat Methodol. 2020;8(2):304-324. doi:10.1093/jssam/smy028PubMedGoogle ScholarCrossref
    55.
    Tooher  RL, Middleton  PF, Crowther  CA.  A thematic analysis of factors influencing recruitment to maternal and perinatal trials.   BMC Pregnancy Childbirth. 2008;8:36. doi:10.1186/1471-2393-8-36PubMedGoogle ScholarCrossref
    56.
    Ballard  HO, Shook  LA, Desai  NS, Anand  KJ.  Neonatal research and the validity of informed consent obtained in the perinatal period.   J Perinatol. 2004;24(7):409-415. doi:10.1038/sj.jp.7211142PubMedGoogle ScholarCrossref
    57.
    Guillemin  M, Barnard  E, Allen  A,  et al  Do research participants trust researchers or their institution?   J Empir Res Hum Res Ethics. 2018;13(3):285-294. doi:10.1177/1556264618763253Google ScholarCrossref
    58.
    Weiss  EM, Barg  FK, Cook  N, Black  E, Joffe  S.  Parental decision-making preferences in neonatal intensive care.   J Pediatr. 2016;179:36-41.e3. doi:10.1016/j.jpeds.2016.08.030PubMedGoogle ScholarCrossref
    59.
    Weiss  EM, Xie  D, Cook  N, Coughlin  K, Joffe  S.  Characteristics associated with preferences for parent-centered decision making in neonatal intensive care.   JAMA Pediatr. 2018;172(5):461-468. doi:10.1001/jamapediatrics.2017.5776PubMedGoogle ScholarCrossref
    ×