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Trials
Published in: Trials 1/2016

Open Access 01-12-2016 | Research

Stakeholders’ views on the ethical challenges of pragmatic trials investigating pharmaceutical drugs

Authors: Shona Kalkman, Ghislaine J. M. W. van Thiel, Diederick E. Grobbee, Anna-Katharina Meinecke, Mira G. P. Zuidgeest, Johannes J. M. van Delden, on behalf of Work Package 3 of the IMI GetReal Consortium

Published in: Trials | Issue 1/2016

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Abstract

Background

We explored the views of key stakeholders to identify the ethical challenges of pragmatic trials investigating pharmaceutical drugs. A secondary aim was to capture stakeholders’ attitudes towards the implementation of pragmatic trials in the drug development process.

Methods

We conducted semistructured, in-depth interviews among individuals from different key stakeholder groups (academia and independent research institutions, the pharmaceutical industry, regulators, Health Technology Assessment (HTA) agencies and patients’ organizations) through telephone or face-to-face sessions. Interviews were structured around the question “what challenges were experienced or perceived during the design, conduct and/or review of pragmatic trials.” Respondents were additionally asked about their views on implementation of pragmatic trials in the drug development process. Thematic analysis was used to identify the ethically relevant features across data sets.

Results

We interviewed 34 stakeholders in 25 individual sessions and four group sessions. The four perceived challenges of ethical relevance were: (1) less controlled conditions creating safety concerns, (2) comparison with usual care potentially compromising clinical equipoise, (3) tailored or waivers of informed consent affecting patient autonomy, and (4) minimal interference with “real-world” practice reducing the knowledge value of trial results.

Conclusions

We identified stakeholder concerns regarding risk assessment, use of suboptimal usual care as a comparator, tailoring of informed consent procedures and ensuring the social value of pragmatic trials. These concerns increased when respondents were asked about pragmatic trials conducted before market authorization.
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Literature
1.
Rothwell PM. External validity of randomised controlled trials: “to whom do the results of this trial apply?”. Lancet. 2005;365(9453):82–93.CrossRefPubMed
2.
Califf RM, Zarin DA, Kramer JM, Sherman RE, Aberle LH, Tasneem A. Characteristics of clinical trials registered in ClinicalTrials.gov, 2007–2010. JAMA. 2012;307:1838–47.CrossRefPubMed
3.
4.
Loudon K, Zwarenstein M, Sullivan F, Donnan P, Treweek S. Making clinical trials more relevant: improving and validating the PRECIS tool for matching trial design decisions to trial purpose. Trials. 2013;14:115.CrossRefPubMedPubMedCentral
5.
Eapen ZJ, Lauer MS, Temple RJ. The imperative of overcoming barriers to the conduct of large, simple trials. JAMA. 2014;311(14):1397–8.CrossRefPubMed
6.
Tunis SR, Stryer DB, Clancy CM. Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy. JAMA. 2003;290(12):1624–32.CrossRefPubMed
7.
Van Staa TP, Goldacre B, Gulliford M, Cassell J, Pirmohamed M, Taweel A, Delaney B, Smeeth L. Pragmatic randomised trials using routine electronic health records: putting them to the test. BMJ. 2012;344:e55.CrossRefPubMedPubMedCentral
8.
Chalkidou K, Tunis S, Whicher D, Fowler R, Zwarenstein M. The role for pragmatic randomized controlled trials (pRCTs) in comparative effectiveness research. Clin Trials. 2012;9(4):436–46.CrossRefPubMed
9.
Platt R, Kass NE, McGraw D. Ethics, regulation, and comparative effectiveness research: time for a change. JAMA. 2014;311(15):1497–8.CrossRefPubMed
10.
Schwartz D, Lellouch J. Explanatory and pragmatic attitudes in therapeutical trials. J Clin Epidemiol. 2009;62(5):499–505.CrossRefPubMed
11.
Grobbee DE, Hoes AW. Clinical Epidemiology: Principles, Methods and Applications for Clinical Research. 2nd ed. Burlington (MA), USA: Jones & Bartlett Learning; 2015.
12.
Thorpe KE, Zwarenstein M, Oxman AD, Treweek S, Furberg CD, Altman DG, Tunis S, Bergel E, Harvey I, Magid DJ, Chalkidou K. A pragmatic-explanatory continuum indicator summary (PRECIS): a tool to help trial designers. J Clin Epidemiol. 2009;62(5):464–75.CrossRefPubMed
13.
14.
Ali J, Califf R, Sugarman J. Anticipated ethics and regulatory challenges in PCORnet: The National Patient-Centered Clinical Research Network. Account Res. 2016;23(2):79–96.CrossRefPubMed
15.
16.
17.
Califf RM, Sugarman J. Exploring the ethical and regulatory issues in pragmatic clinical trials. Clin Trials. 2015;12(5):436–41.CrossRefPubMed
18.
Sugarman J, Califf RM. Ethics and regulatory complexities for pragmatic clinical trials. JAMA. 2014;311(23):2381–2.CrossRefPubMed
19.
McKinney Jr RE, Beskow LM, Ford DE, Lantos JD, McCall J, Patrick-Lake B, Pletcher MJ, Rath B, Schmidt H, Weinfurt K. Use of altered informed consent in pragmatic clinical research. Clin Trials. 2015;12(5):494–502.CrossRefPubMedPubMedCentral
20.
Welch MJ, Lally R, Miller JE, Pittman S, Brodsky L, Caplan AL, Uhlenbrauck G, Louzao DM, Fischer JH, Wilfond B. The ethics and regulatory landscape of including vulnerable populations in pragmatic clinical trials. Clin Trials. 2015;12(5):503–10.CrossRefPubMed
21.
Kalkman S, van Thiel GJMW, Grobbee DE, van Delden JJM. Pragmatic randomized trials in drug development pose new ethical questions. Drug Discov Today. 2015;20(7):856–62.CrossRefPubMed
22.
Ali J, Andrews JE, Somkin CP, Rabinovich CE. Harms, benefits, and the nature of interventions in pragmatic clinical trials. Clin Trials. 2015;12(5):467–75.CrossRefPubMed
23.
Creswell JW. Qualitative Inquiry and Research Design: Choosing among Five Traditions. 3rd ed. Thousand Oaks: SAGE Publications Ltd.; 2013.
24.
25.
Guest G, Brunce A, Johnson L. How many interviews are enough? An experiment with data saturation and variability. Field Methods. 2006;18:59–82.CrossRef
26.
Boeije H. Analysis in Qualitative Research. Thousand Oaks: SAGE Publications Inc.; 2012.
27.
Tong A, Sainsbury P, Craig J. Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. Int J Qual Health Care. 2007;19(6):349–57.CrossRefPubMed
28.
SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network, Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG, Laptook AR, Yoder BA, Faix RG, Das A, Poole WK, Schibler K, Newman NS, Ambalavanan N, Frantz 3rd ID, Piazza AJ, Sánchez PJ, Morris BH, Laroia N, Phelps DL, Poindexter BB, Cotten CM, Van Meurs KP, Duara S, Narendran V, Sood BG, O’Shea TM, Bell EF, Ehrenkranz RA, Watterberg KL, Higgins RD. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med. 2010;362(21):1959–69.CrossRefPubMedCentral
29.
30.
Dawson L, Zarin DA, Emanuel EJ, Friedman LM, Chaudhari B, Goodman SN. Considering usual medical care in clinical trial design. PLoS Med. 2009;6(9):e1000111.CrossRefPubMedPubMedCentral
31.
Kass NE, Faden RR, Goodman SN, Pronovost P, Tunis S, Beauchamp TL. The research-treatment distinction: a problematic approach for determining which activities should have ethical oversight. Hastings Cent Rep. 2013;Spec No:S4–15.CrossRefPubMed
32.
33.
34.
Kim SY, Miller FG. Informed consent for pragmatic trials—the integrated consent model. N Engl J Med. 2014;370(8):769–72.CrossRefPubMed
35.
Whicher D, Kass N, Faden R. Stakeholders’ views of alternatives to prospective informed consent for minimal-risk pragmatic comparative effectiveness trials. J Law Med Ethics. 2015;43(2):397–409.PubMed
36.
Faden R, Kass N, Whicher D, Stewart W, Tunis S. Ethics and informed consent for comparative effectiveness research with prospective electronic clinical data. Med Care. 2013;51(8 Suppl 3):S53–7.CrossRefPubMed
Metadata
Title
Stakeholders’ views on the ethical challenges of pragmatic trials investigating pharmaceutical drugs
Authors
Shona Kalkman
Ghislaine J. M. W. van Thiel
Diederick E. Grobbee
Anna-Katharina Meinecke
Mira G. P. Zuidgeest
Johannes J. M. van Delden
on behalf of Work Package 3 of the IMI GetReal Consortium
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Trials / Issue 1/2016
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-016-1546-3

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