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Variation among institutional review boards in evaluating the design of a multicenter randomized trial

Journal of Perinatology volume 30, pages 163–169 (2010)Cite this article

Abstract

Objective:

The objective of the study was to examine the variation among institutional review boards (IRBs) in evaluation of the study design of a multicenter trial.

Study Design:

We assessed the first written response of local IRBs to each site investigator for a multicenter trial of vitamin A supplementation in extremely low birth weight (ELBW) infants performed by the National Institute of Child Health and Human Development Neonatal Research Network. Each author of this paper independently reviewed and categorized IRB concerns as major, minor or none, according to the predefined criteria.

Result:

Initially, 9 of 18 IRBs withheld approval because of at least one major concern. These concerns reflected difficulties in evaluating specific scientific issues for the design of the trial, including its justification, enrollment criteria, control and experimental therapies, co-interventions, toxicity assessment, outcome monitoring and informed consent.

Conclusion:

The difficulty in assessing appropriate trial design for the specific hypothesis under investigation resulted in considerable variability in the evaluation by local IRBs.

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References

  1. Garfield P . Cross district comparison of applications to research ethics committees. BMJ 1995; 31: 660–662.

    Article  Google Scholar 

  2. Redshaw ME, Harris A, Baum JD . Research ethics committee audit: differences between committees. J Med Ethics 1996; 22: 78–82.

    Article  CAS  Google Scholar 

  3. Silverman H, Chandros Hill S, Sugarman J . Variability between institutional review board's decisions within the context of a multicenter trial. Crit Care Med 2001; 29: 235–241.

    Article  CAS  Google Scholar 

  4. Stair TO, Reed CR, Raideos MS, Koski G, Camargo CA . Variation in institutional review board responses to a standard protocol for a multicenter clinical trial. Academic Emerg Med 2001; 636–641.

    Article  CAS  Google Scholar 

  5. McWilliams R, Hoover-Fong J, Hamosh A, Beck S, Beaty T, Cutting G . Problematic variation in local institutional review of a multicenter genetic epidemiology study. JAMA 2003; 290: 360–366.

    Article  Google Scholar 

  6. Mansbach J, Acholonu U, Clark S, Camargo Jr CA . Variation in institutional review board responses to a standard, observational, pediatric research protocol. Acad Emerg Med 2007; 14: 377–380.

    Article  Google Scholar 

  7. Green LA, Lowery JC, Kowalski CP, Wyszewianski L . Impact of institutional review board practice variation on observational health services research. Health Serv Res 2006; 41: 214–230.

    Article  Google Scholar 

  8. Kimberly MB, Hoehn KS, Feudtner C, Nelson RM, Schreiner M . Variation in standards of research compensation and child assent practices: a comparison of 69 institutional review board-approved informed permission and assent forms for 3 multicenter pediatric clinical trials. Pediatrics 2006; 117: 1706–1711.

    Article  Google Scholar 

  9. Dziak K, Anderson R, Sevick MA, Weisman CS, Levine DW, Scholle SH . Variations among institutional review board reviews in a multisite health services research study. Health Serv Res 2005; 40: 279–290.

    Article  Google Scholar 

  10. Vick CC, Finan KR, Kiefe C, Neumayer L, Hawn MT . Variation in institutional review processes for a multisite observational study. Am J Surg 2005; 190: 805–809.

    Article  Google Scholar 

  11. Clark S, Pelletier AJ, Brenner BE, Lang DM, Strunk RC, Camargo CA . Feasibility of a national fatal asthma registry: more evidence of IRB variation in evaluation of a standard protocol. J Asthma 2006; 43: 19–23.

    Article  Google Scholar 

  12. Burman W, Breese P, Weis S, Bock N, Bernardo J, Vernon A et al. The effects of local review on informed consent documents from a multicenter clinical trials consortium. Control Clin Trials 2003; 24: 245–255.

    Article  Google Scholar 

  13. Tyson JE, Wright LL, Oh W, Kennedy KA, Mele L, Ehrenkranz RA et al. Vitamin A supplementation for extremely-low-birth-weight infants. N Engl J Med 1999; 340: 1962–1968.

    Article  CAS  Google Scholar 

  14. Ambalavanan N, Tyson JE, Kennedy KA, Hansen NI, Vohr BR, Wright LL et al. Vitamin A supplementation for extremely low birth weight infants: outcome at 18-22 months. Pediatrics 2005; 115: e249–e254.

    Article  Google Scholar 

  15. Kennedy KA, Stoll BJ, Ehrenkranz RA, Oh W, Wright LL, Stevenson DK et al. Vitamin A to prevent bronchopulmonary dysplasia in very-low-birth-weight infants: Has the dose been too low? The NICHD Neonatal Research Network. Early Hum Dev 1997; 49: 19–31.

    Article  CAS  Google Scholar 

  16. Drazen JM . Controlling research trials. N Engl J Med 2003; 348: 1377–1380.

    Article  Google Scholar 

  17. Freedman B . Equipoise and the ethics of clinical research. N Engl J Med 1987; 317: 141–145.

    Article  CAS  Google Scholar 

  18. Fisher ES, Welch HG . Avoiding the unintended consequences of growth in medical care. How might more be worse? JAMA 1999; 281: 446–453.

    Article  CAS  Google Scholar 

  19. Lacchetti C, Guyatt G . Therapy and validity. Surprising results of randomized controlled trials. In: Guyatt G, Rennie D (eds) Users’ Guide to the Medical Literature. A Manual for Evidence-Based Clinical Practice. AMA Press: Chicago, 2002, pp. 247–265.

    Google Scholar 

  20. Silverman WA . Overtreatment of newborns? A personal retrospective. Pediatrics 1992; 90: 971–976.

    CAS  PubMed  Google Scholar 

  21. Tyson J . Use of unproven therapies in clinical practice and research: how can we better serve our patients and their families? Semin Perinatol 1995; 19: 98–111.

    Article  CAS  Google Scholar 

  22. Office for Human Research Protections. US Department of Health and Human Services: IRB Guidebook http://www.hhs.gov/ohrp/irb/irb_guidebook.htm

  23. Ehrenkranz RA, Mercurio MR . Bronchopulmonary dysplasia. In: Sinclair JC, Bracken M (eds) Effective Care of the Newborn Infant. Oxford University Press: New York, 1992 p. 403.

    Google Scholar 

  24. Jadad AR, Rennie D . The randomized controlled trial gets a middle–aged checkup. JAMA 1998; 279: 319–320.

    Article  CAS  Google Scholar 

  25. Guyatt G, Cook D, Devereaux PJ, Meade M, Straus S . Therapy. In: Guyatt G, Rennie D (eds) Users’ Guide to the Medical Literature. A Manual for Evidence-Based Clinical Practice. AMA Press: Chicago, 2002 pp. 55–79.

    Google Scholar 

  26. Oxman A, Guyatt G, Cook D, Montori V . Summarizing the evidence. In: Guyatt G, Rennie D (eds) Users’ Guide to the Medical Literature. A Manual for Evidence-Based Clinical Practice. AMA Press: Chicago, 2002 pp. 155–171.

    Google Scholar 

  27. Sinclair JC, Cook RJ, Guyatt GH, Pauker SG, Cook DJ . When should an effective treatment be used? Derivation of the threshold number needed to treat and the minimum event rate for treatment. J Clin Epidemiol 2001; 54: 253–262.

    Article  CAS  Google Scholar 

  28. Bracken MB, Sinclair JC . When can odds ratios mislead? BMJ 1998; 317: 1156–1157.

    CAS  PubMed  Google Scholar 

  29. Tully J, Ninis N, Booy R, Viner R . The new system of review by multicenter research ethics committees: prospective study. BMJ 2000; 320: 1179–1182.

    Article  CAS  Google Scholar 

  30. Thornquist MD, Edelstein C, Goodman GE, Omenn GS . Streamlining IRB review in multisite trials through single study IRB cooperative agreements. Experience of the Beta-Carotene and Retinol Efficacy Trial (Caret). Control Clin Trials 2002; 23: 80–86.

    Article  Google Scholar 

  31. Christian MC, Goldberg JL, Killen J, Abrams JS, McCabe MS, Mauer JK et al. A central institutional review board for multi-institutional trials. N Engl J Med 2002; 346: 1405–1408.

    Article  Google Scholar 

  32. Emanuel EJ, Miller FG . The ethics of placebo-controlled trials—A middle ground. N Engl J Med 2001; 345: 915–919.

    Article  CAS  Google Scholar 

  33. Fanaroff AA, Korones SB, Wright LL, Wright EC, Poland RL, Bauer CB et al. A controlled trial of intravenous immunoglobulin to reduce nosocomial infections in very low birth weight infants. N Engl J Med 1994; 330: 1107–1113.

    Article  CAS  Google Scholar 

  34. Van Lingen RA, Simons SH, Anderson BJ, Tibboel D . The effects of analgesia in the vulnerable infant during the perinatal period. Clin Perinatol 2002; 29: 511–534.

    Article  CAS  Google Scholar 

  35. Hrobjartsson A, Gotzsche PC . Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. N Engl J Med 2001; 344: 1594–15602.

    Article  CAS  Google Scholar 

  36. Yusuf S, Collins R, Peto R . Why do we need some large, simple randomized trials? Stat Med 1984; 3: 409–420.

    Article  CAS  Google Scholar 

  37. Fletcher RW, Fletcher SW . Clinical Epidemiology.The Essentials. 4th edn Lippincott Williams, and Wilkins: Philadelphia, 2005 pp 137–138.

    Google Scholar 

  38. Sackett DL, Straus SE, Richardson WS, Rosenberg W, Haynes RB . Evidence-Based Medicine.How to Practice and Teach EBM. 2nd edn Churchill Livingstone: New York, 2000 pp 69–70.

    Google Scholar 

  39. Bendich A, Langseth L . Safety of vitamin A. Am J Clin Nutr 1989; 49: 358–371.

    Article  CAS  Google Scholar 

  40. West Jr KP, Khatry SK, LeClerq SC, Adhikari R, See L, Katz J et al. Tolerance of young infants to a single, large dose of vitamin A: a randomized community trial in Nepal. Bull World Health Organ 1992; 70: 733–739.

    PubMed  PubMed Central  Google Scholar 

  41. Agoestina T, Humphrey JH, Taylor GA, Usman A, Subardja D, Hidayat S et al. Safety of one 52-mumol (50 000 IU) oral dose of vitamin A administered to neonates. Bull World Health Organ 1994; 72: 859–868.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Eidelman AI, Hoffman NW, Kaitz M . Cognitive deficits in women after childbirth. Obstet Gynecol 1993; 81: 764–767.

    CAS  PubMed  Google Scholar 

  43. Lantos J . The ‘inclusion benefit’ in clinical trials. J Pediatr 1999; 134: 130–131.

    Article  CAS  Google Scholar 

  44. Broyles S, Sharp C, Tyson J, Sadler J . How should parents be informed about major procedures? An exploratory trial in the neonatal period. Early Hum Dev 1992; 31: 67–75.

    Article  CAS  Google Scholar 

  45. Emanuel EJ, Wendler D, Grady C . What makes clinical research ethical? JAMA 2000; 283: 2701–2711.

    Article  CAS  Google Scholar 

  46. Vist GE, Bryant D, Somerville L, Birmingham T, Oxman AD . Outcomes of patients who participate in randomized controlled trials compared to similar patients receiving similar interventions who do not participate. Cochrane Database Syst Rev 2008; (3): MR000009.

  47. Schmidt B, Gillie P, Caco C, Roberts J, Roberts R . Do sick newborn infants benefit from participation in a randomized clinical trial? J Pediatr 1999; 134: 151–155.

    Article  CAS  Google Scholar 

  48. Tyson JE, Knudson PL . Views of neonatologists and parents on consent for clinical trials. Lancet 2000; 356: 2026.

    Article  CAS  Google Scholar 

  49. Burman WJ, Reeves RR, Cohn DL, Schooley R . Breaking the camel's back: multicenter clinical trials and local institutional review boards. Ann Int Med 2001; 134: 152–157.

    Article  CAS  Google Scholar 

  50. DeMets DL, Fost N, Powers M . An institutional review board dilemma: responsible for safety monitoring but not in control. Clin Trials 2006; 3: 142–148.

    Article  Google Scholar 

  51. Morse MA, Califf RM, Sugarman J . Monitoring and ensuring safety during clinical research. JAMA 2001; 285: 1201–1205.

    Article  CAS  Google Scholar 

  52. Gold JL, Dewa CS . Institutional review boards and multisite studies in health services research: is there a better way? Health Serv Res 2005; 40: 291–307.

    Article  Google Scholar 

  53. National Bioethics Advisory Commission. Ethical and policy issues in research involving human participants. 2001. Bethesda, MD. (summary), pp 16–17. http://bioethics.georgetown.edu/nabc/pubs.html.

  54. Goldman J, Katz MD . Inconsistency and institutional review boards. JAMA 1982; 248: 197–202.

    Article  CAS  Google Scholar 

  55. Clark DC . Variability between institutional review boards and the value of local research context. Crit Care Med 2001; 29: 444–445.

    Article  CAS  Google Scholar 

  56. Schneider CE . The Practice of Autonomy. Patients, Doctors, and Medical Decisions. Oxford University Press: New York, 1998.

    Google Scholar 

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Acknowledgements

The National Institutes of Health and the National Institute of Child Health and Human Development provided grant support for recruitment and data analysis for the Neonatal Research Network's Vitamin A Supplementation Study for 1996 and 1997. The funding agencies provided overall oversight for study conduct, but all data analyses and interpretation were independent of the funding agencies. We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study. The following investigators participated in this study: NRN Steering Committee Chair: Alan Jobe, University of Cincinnati; Brown University Women & Infants Hospital of Rhode Island (U10 HD27904)—William Oh and Angelita Hensman; Case Western Reserve University Rainbow Babies & Children's Hospital (GCRC M01 RR80, U10 HD21364)—Avroy A Fanaroff, Michele C Walsh and Nancy S Newman; Emory University Children's Healthcare of Atlanta, Grady Memorial Hospital, and Emory Crawford Long Hospital (GCRC M01 RR39, U10 HD27851)—Barbara J Stoll and Ellen Hale; Harvard Medical School Brigham and Women's Hospital (GCRC M01 RR2172, GCRC M01 RR2635, U10 HD34167)—Ann R Stark and Kerri Fournier; Indiana University Indiana University Hospital, Methodist Hospital, Riley Hospital for Children, and Wishard Health Services (GCRC M01 RR750, U10 HD27856)—James A Lemons and Diana D Appel; National Institute of Child Health and Human Development—Linda L Wright and Elizabeth M McClure; Research Triangle Institute (U01 HD36790)—W Kenneth Poole, Abhik Das and Betty Hastings; Stanford University Lucile Packard Children's Hospital (U10 HD27880)—David K Stevenson and M Bethany Ball; University of Alabama at Birmingham Health System and Children's Hospital of Alabama (U10 HD34216)—Waldemar A Carlo and Monica V Collins; University of Cincinnati University Hospital, Cincinnati Children's Hospital Medical Center, and Good Samaritan Hospital (GCRC M01 RR8084, U10 HD27853)—Edward F Donovan and Marcia Mersmann; University of Miami Holtz Children's Hospital (U10 HD21397)—Charles Bauer and AM Worth; University of New Mexico Health Sciences Center (GCRC M01 RR997, U10 HD27881)—Lu-Ann Papile and Conra Backstrom Lacy; University of Tennessee (U10 HD21415)—Sheldon B Korones and Tina Hudson; University of Texas Southwestern Medical Center at Dallas Parkland Health & Hospital System and Children's Medical Center Dallas (GCRC M01 RR633, U10 HD40689)—Jon E Tyson and Susie Madison; Wayne State University Hutzel Women's Hospital and Children's Hospital of Michigan (U10 HD21385)—Seetha Shankaran and Geraldine Muran; Yale University Yale-New Haven Children's Hospital (GCRC M01 RR6022, U10 HD27871)—Richard A Ehrenkranz and Patricia Gettner.

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Authors and Affiliations

  1. Department of Pediatrics, Section of Neonatology, Baylor College of Medicine, Houston, TX, USA

    A R Stark

  2. Center for Clinical Research and Evidence Based Medicine, University of Texas Health Science Center at Houston Medical School, Houston, TX, USA

    J E Tyson

  3. Center for Global Health Research, Tufts University School of Medicine, Boston, MA, USA

    P L Hibberd

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  1. A R Stark
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Correspondence to A R Stark.

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Stark, A., Tyson, J. & Hibberd, P. Variation among institutional review boards in evaluating the design of a multicenter randomized trial. J Perinatol 30, 163–169 (2010). https://doi.org/10.1038/jp.2009.157

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