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Published in: Trials 1/2017

Open Access 01-12-2017 | Review

Sharing interim trial results by the Data Safety Monitoring Board with those responsible for the trial’s conduct and progress: a narrative review

Authors: Victoria Borg Debono, Lawrence Mbuagbaw, Lehana Thabane

Published in: Trials | Issue 1/2017

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Abstract

Background

Sharing interim data, results or result extrapolations is an important issue that can affect trial integrity. The different ways in which Data Safety Monitoring Boards (DSMBs) share interim results with non-DSMB members and the acceptability of such practices are poorly understood. Our objective was to undertake a narrative review specifically on what kind of interim results, if any, should be shared by the DSMB with non-DSMB members and why.

Methods

We conducted a narrative review using a systematic search strategy of several databases and major health research stakeholders. Literature was included if there was some discussion within the full text about sharing interim trial results with non-DSMB members.

Results

About 79.6% (129/162) of included citations were based on author’s views, 16.7% (27/162) on research guidelines and 3.7% (6/162) on surveys. The largest group of citations, 73/162 (45%), expresses the opinion or argument against sharing interim results with exceptions. Trailing closely, 71/162 (43.8%) of the included citations support the opinion or argument that interim results should not be shared and should remain confidential with the DSMB. Half of the six surveys support sharing in some capacity, while the other three do not. Eleven circumstances were found that potentially warrant interim result sharing by the DSMB; they relate to (1) usual practices by DSMBs, (2) trial completion threatened, (3) patient safety, (4) regulatory approval and (5) other circumstances. Dominant risks for sharing under these conditions are associated with introducing trial bias.

Discussion/conclusion

There was no majority view in the literature. However, the largest group of citations included express the idea that interim results should remain confidential with the DSMB but also acknowledge circumstances when they could be shared with non-DSMB members. Limitations of this review are that (1) the included literature predominately provides personal perspectives, not evidence, and (2) surveys found globally focus on trial monitoring practices lacking detailed information on what specifically to share, with whom and why. More research is needed with the use of a detailed survey of the clinical trial community focused on DSMB sharing interim results, to better understand and guide DSMB interim result sharing practices.
Appendix
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Literature
1.
Ellenberg SS, Fleming TR, DeMets DL. Data monitoring committees in clinical trials: a practical perspective. Hoboken: John Wiley & Sons; 2003.
2.
Herson J. Data and safety monitoring committees in clinical trials. Boca Raton: Chapman & Hall/CRC/Taylor & Francis; 2009.CrossRef
3.
Anand SS, Wittes J, Yusuf S. What information should a sponsor of a randomized trial receive during its conduct? Clin Trials. 2011;8:716–9.CrossRefPubMed
4.
Friedman LM, Furberg C, DeMets DL. Fundamentals of clinical trials. 3rd ed. New York: Springer; 1998.CrossRef
5.
Grant AM, Altman DG, Babiker AB, Campbell MK, Clemens FJ, Darbyshire JH, Elbourne DR, McLeer SK, Parmar MK, Pocock SJ, et al. Issues in data monitoring and interim analysis of trials. Health Technol Assess. 2005;9:1–238. iii–iv.CrossRef
6.
Borer JS, Gordon DJ, Geller NL. When should data and safety monitoring committees share interim results in cardiovascular trials? JAMA. 2008;299:1710–2.CrossRefPubMed
7.
Bloudoff-Indelicato M. Threat of interim data leaks prompts call for international rules. Nat Med. 2015;21:200.CrossRefPubMed
8.
9.
10.
11.
George SL. A survey of monitoring practices in cancer clinical trials. Stat Med. 1993;12(5-6):435–50.CrossRefPubMed
12.
Geller NL, Stylianou M. Practical issues in data monitoring of clinical trials: summary of responses to a questionnaire at NIH. Stat Med. 1993;12(5-6):543–51. discussion 553.CrossRefPubMed
13.
Tereskerz PM, Guterbock TM, Kermer DA, Moreno JD. An opinion and practice survey on the structure and management of data and safety monitoring boards. Account Res. 2011;18:1–30.CrossRefPubMed
14.
Silverman H. Ethical issues during the conduct of clinical trials. Proc Am Thorac Soc. 2007;4:180–4. discussion 184.CrossRefPubMed
15.
16.
Fleming TR, Sharples K, McCall J, Moore A, Rodgers A, Stewart R. Maintaining confidentiality of interim data to enhance trial integrity and credibility. Clin Trials. 2008;5:157–67.CrossRefPubMedPubMedCentral
17.
Rouse DJ. Data monitoring and safety committees and their operations. Obstet Gynecol Surv. 2003;58(5):329–36.PubMed
18.
Migrino RQ, Topol EJ. A matter of life and death? The Heart Protection Study and protection of clinical trial participants. Control Clin Trials. 2003;24(5):501–5.CrossRefPubMed
19.
Hemmings R, Day S. Regulatory perspectives on data safety monitoring boards: protecting the integrity of data. Drug Saf. 2004;27:1–6.CrossRefPubMed
20.
US Food and Drug Administration. The establishment and operation of clinical trial data monitoring committees for clinical trial sponsors. Rockville: US Food and Drug Administration; 2006. p. 38.
21.
Eckstein L. Building a more connected DSMB: better integrating ethics review and safety monitoring. Account Res Policies Qual Assur. 2015;22(2):81–105.
22.
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Harmonised tripartite guideline; statistical principles for clinical trials E9. Geneva: ICH; 1998. p. 39.
23.
Chalmers I, Altman DG, McHaffie H, Owens N, Cooke RW. Data sharing among data monitoring committees and responsibilities to patients and science. Trials. 2013;14:102.CrossRefPubMedPubMedCentral
24.
25.
US Food and Drug Administration. FDA guidance on clinical trial data monitoring committees (DMCs). Rockville: US Food and Drug Administration; 2001. p. 237.
26.
Pocock SJ. Statistical and ethical issues in monitoring clinical trials. Stat Med. 1993;12(15-16):1459–69. discussion 1471–5.CrossRefPubMed
27.
Chow SC, Corey R, Lin M. On the independence of data monitoring committee in adaptive design clinical trials. J Biopharm Stat. 2012;22(4):853–67.CrossRefPubMed
28.
Fleming TR, Hennekens CH, Pfeffer MA, DeMets DL. Enhancing trial integrity by protecting the independence of data monitoring committees in clinical trials. J Biopharm Stat. 2014;24(5):968–75.CrossRefPubMedPubMedCentral
29.
D’Agostino Sr RB. The statistician and the data monitoring committee. Stat Med. 2004;23(10):1501–2.CrossRefPubMed
30.
Fleming TR. Standard versus adaptive monitoring procedures: a commentary. Stat Med. 2006;25(19):3305–12. discussion 3313–4, 3326–47.CrossRefPubMed
31.
Siegel JP, O’Neill RT, Temple R, Campbell G, Foulkes MA. Independence of the statistician who analyses unblinded data. Stat Med. 2004;23(10):1527–9.CrossRefPubMed
32.
33.
34.
35.
Williams GW, Davis RL, Getson AJ, Gould AL, Hwang IK, Matthews H, Shih WCJ, Snapinn SM, Waltonbowen KL. Monitoring of clinical trials and interim analyses from a drug sponsors point of view. Stat Med. 1993;12(5-6):481–92.CrossRefPubMed
36.
DeMets D, Califf R, Dixon D, Ellenberg S, Fleming T, Held P, Julian D, Kaplan R, Levine R, Neaton J, et al. Issues in regulatory guidelines for data monitoring committees. Clin Trials. 2004;1(2):162–9.CrossRefPubMed
37.
Delgado-Herrera L, Anbar D. A model for the interim analysis process: a case study. Control Clin Trials. 2003;24:51–65.CrossRefPubMed
38.
DeMets DL, Fleming TR. The independent statistician for data monitoring committees. Stat Med. 2004;23(10):1513–7.CrossRefPubMed
39.
Stephens RJ, Langley RE, Mulvenna P, Nankivell M, Vail A, Parmar MK. Interim results in clinical trials: do we need to keep all interim randomised clinical trial results confidential? Lung Cancer. 2014;85(2):116–8.CrossRefPubMed
40.
Green S, Crowley J. Data monitoring committees for Southwest Oncology Group clinical trials. Stat Med. 1993;12(5-6):451–5.CrossRefPubMed
41.
Lilford RJ, Braunholtz D, Edwards S, Stevens A. Monitoring clinical trials - interim data should be publicly available. Br Med J. 2001;323(7310):441–2.CrossRef
42.
Miller FG, Wendler D. Is it ethical to keep interim findings of randomised controlled trials confidential? J Med Ethics. 2008;34:198–201.CrossRefPubMed
43.
Vail A, Hornbuckle J, Spiegelhalter DJ, Thornton JG. Prospective application of Bayesian monitoring and analysis in an ‘open’ randomized clinical trial. Stat Med. 2001;20(24):3777–87.CrossRefPubMed
44.
Fleming TR, Ellenberg S, DeMets DL. Monitoring clinical trials: issues and controversies regarding confidentiality. Stat Med. 2002;21(19):2843–51.CrossRefPubMed
45.
Glover JM, Kay R. Who advises the Data Monitoring Committee (DMC)? A review of regulatory guidance for sponsors on DMCs after 5 years and advice for DMC members. Drug Inf J. 2012;46(5):525–31.
46.
Califf RM, Ellenberg SS. Statistical approaches and policies for the operations of Data and Safety Monitoring Committees. Am Heart J. 2001;141(2):301–5.CrossRefPubMed
47.
Hicks LK, Laupacis A, Slutsky AS. A primer on data safety monitoring boards: mission, methods, and controversies. Intensive Care Med. 2007;33(10):1815–8.CrossRefPubMed
48.
DeMets DL. Relationships between Data Monitoring Committees. Control Clin Trials. 2000;21(1):54–5.CrossRef
49.
Dixon DO, Lagakos SW. Should data and safety monitoring boards share confidential interim data? Control Clin Trials. 2000;21:1–6. discussion 54–55.CrossRefPubMed
50.
Dixon DO, Weiss S, Cahill K, Fox L, Love J, McNamara J, Soto-Torres LE. Data and safety monitoring policy for National Institute of Allergy and Infectious Diseases clinical trials. Clin Trials. 2011;8:727–35.CrossRefPubMed
51.
Yusuf, Whitley R, Assenzo R, Fleming T, Deykin, Hawkins B, Meier, Gent, Tognoni, Ellenberg J, et al. The operation of data monitoring committees - discussion. Stat Med. 1993;12(5-6):527–42.CrossRef
52.
Ellenberg SS. Independent data monitoring committees: rationale, operations and controversies. Stat Med. 2001;20:2573–83.CrossRefPubMed
53.
Wittes J, Barrett-Connor E, Braunwald E, Chesney M, Cohen HJ, Demets D, Dunn L, Dwyer J, Heaney RP, Vogel V, et al. Monitoring the randomized trials of the Women’s Health Initiative: the experience of the Data and Safety Monitoring Board. Clin Trials. 2007;4:218–34.CrossRefPubMed
54.
Peppercorn J, Buss WG, Fost N, Godley PA. The dilemma of data-safety monitoring: provision of significant new data to research participants. Lancet. 2008;371(9611):527–9.CrossRefPubMed
55.
Fleming TR. Protecting the confidentiality of interim data: addressing current challenges. Clin Trials. 2015;12(1):5–11.CrossRefPubMed
56.
Nissen SE. Commentary: confidentiality of interim trial data—the emerging crisis. Clin Trials. 2015;12(1):15–7.CrossRefPubMed
57.
US Food and Drug Administration, Department of Health and Human Services, Parks M, Rosebraugh C, Jenkins J, Woodcock J. Memorandum; disclosure of interim cardiovascular risk study data NDA 22271 Nesina (alogliptin) tablets and its fixed dose combination product NDAs 22426 and 203414. Rockville: US Food and Drug Administration; 2013.
58.
US Food and Drug Administration. Presentations for: Part 15 public hearing; confidentiality of interim results in cardiovascular (CV) outcomes safety trials. Rockville: US Food and Drug Administration; 2014.
59.
London AJ. Commentary: data monitoring confidentiality and FDA transparency. Clin Trials. 2015;12(1):12–4.CrossRefPubMed
60.
US Food and Drug Administration. Transcript for hearing: Part 15 public hearing; confidentiality of interim results in cardiovascular (CV) outcomes safety trials. Rockville: US Food and Drug Administration; 2014.
61.
62.
63.
Gallo P, Chuang-Stein C, Dragalin V, Gaydos B, Krams M, Pinheiro J. Adaptive designs in clinical drug development—an Executive Summary of the PhRMA Working Group. J Biopharm Stat. 2006;16(3):275–83. discussion 285–91, 293–8, 311–2.CrossRefPubMed
64.
Gallo P. Confidentiality and trial integrity issues for adaptive designs. Drug Inf J. 2006;40(4):445–50.
65.
Herson J. Coordinating data monitoring committees and adaptive clinical trial designs. Drug Inf J. 2008;42(4):297–301.
66.
Antonijevic Z, Gallo P, Chuang-Stein C, Dragalin V, Loewy J, Menon S, Miller ER, Morgan CC, Sanchez M. Views on emerging issues pertaining to data monitoring committees for adaptive trials. Ther Innov Regul Sci. 2013;47(4):495–502.CrossRef
67.
Day S. Data monitoring committees in clinical trials: best practice, complexities and considerations. Clin Invest. 2015;5(7):615–7.CrossRef
68.
Gallo P, Fardipour P, Dragalin V, Krams M, Littman GS, Bretz F. Data monitoring in adaptive dose-ranging trials. Stat Biopharm Res. 2010;2(4):513–21.CrossRef
69.
Korn EL, Hunsberger S, Freidlin B, Smith MA, Abrams JS. Preliminary data release for randomized clinical trials of noninferiority: a new proposal. J Clin Oncol. 2005;23:5831–6.CrossRefPubMed
70.
Allardyce RA, Bagshaw PF, Frampton CM, Frizelle FA, Hewett PJ, Rieger NA, Smith JS, Solomon MJ, Stevenson AR. Ethical issues with the disclosure of surgical trial short-term data. ANZ J Surg. 2011;81(3):125–31.CrossRefPubMed
71.
72.
Rockhold FW, Enas GG. Data monitoring and interim analyses in the pharmaceutical industry: ethical and logistical considerations. Stat Med. 1993;12(5-6):471–9.CrossRefPubMed
73.
DeMets DL, Fleming TR, Whitley RJ, Childress JF, Ellenberg SS, Foulkes M, Mayer KH, O’Fallon J, Pollard RB, Rahal JJ, et al. The data and safety monitoring board and acquired immune deficiency syndrome (AIDS) clinical trials. Control Clin Trials. 1995;16:408–21.CrossRefPubMed
74.
Smith MA, Ungerleider RS, Korn EL, Rubinstein L, Simon R. Role of independent data-monitoring committees in randomized clinical trials sponsored by the National Cancer Institute. J Clin Oncol. 1997;15(7):2736–43.CrossRefPubMed
Metadata
Title
Sharing interim trial results by the Data Safety Monitoring Board with those responsible for the trial’s conduct and progress: a narrative review
Authors
Victoria Borg Debono
Lawrence Mbuagbaw
Lehana Thabane
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Trials / Issue 1/2017
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-017-1858-y

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