دورية أكاديمية
أعرض في EDS

Design characteristics, risk of bias, and reporting of randomised controlled trials supporting approvals of cancer drugs by European Medicines Agency, 2014-16: cross sectional analysis.

التفاصيل البيبلوغرافية
العنوان: Design characteristics, risk of bias, and reporting of randomised controlled trials supporting approvals of cancer drugs by European Medicines Agency, 2014-16: cross sectional analysis.
المؤلفون: Naci H; Department of Health Policy, London School of Economics and Political Science, London WC2A 2AE, UK h.naci@lse.ac.uk.; Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Davis C; Department of Global Health and Social Medicine, King's College London, London, UK., Savović J; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; The National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West (NIHR CLAHRC West) at University Hospitals Bristol NHS Foundation Trust, Bristol, UK., Higgins JPT; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; The National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West (NIHR CLAHRC West) at University Hospitals Bristol NHS Foundation Trust, Bristol, UK.; National Institute for Health Research Bristol Biomedical Research Centre, Bristol, UK., Sterne JAC; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; National Institute for Health Research Bristol Biomedical Research Centre, Bristol, UK., Gyawali B; Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Cancer Research Institute, Queen's University at Kingston, Kingston, Ontario, Canada., Romo-Sandoval X; Department of Health Policy, London School of Economics and Political Science, London WC2A 2AE, UK., Handley N; Department of Global Health and Social Medicine, King's College London, London, UK., Booth CM; Cancer Research Institute, Queen's University at Kingston, Kingston, Ontario, Canada.
المصدر: BMJ (Clinical research ed.) [BMJ] 2019 Sep 18; Vol. 366, pp. l5221. Date of Electronic Publication: 2019 Sep 18.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: British Medical Association Country of Publication: England NLM ID: 8900488 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-1833 (Electronic) Linking ISSN: 09598138 NLM ISO Abbreviation: BMJ Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : British Medical Association
مواضيع طبية MeSH: Antineoplastic Agents/*therapeutic use , Drug Approval/*methods , Neoplasms/*drug therapy , Randomized Controlled Trials as Topic/*methods, Bias ; Cross-Sectional Studies ; Drug and Narcotic Control ; Humans ; Research Design ; Research Report
مستخلص: Objective: To examine the design characteristics, risk of bias, and reporting adequacy of pivotal randomised controlled trials of cancer drugs approved by the European Medicines Agency (EMA).
Design: Cross sectional analysis.
Setting: European regulatory documents, clinical trial registry records, protocols, journal publications, and supplementary appendices.
Eligibility Criteria: Pivotal randomised controlled trials of new cancer drugs approved by the EMA between 2014 and 2016.
Main Outcome Measures: Study design characteristics (randomisation, comparators, and endpoints); risk of bias using the revised Cochrane tool (bias arising from the randomisation process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result); and reporting adequacy (completeness and consistency of information in trial protocols, publications, supplementary appendices, clinical trial registry records, and regulatory documents).
Results: Between 2014 and 2016, the EMA approved 32 new cancer drugs on the basis of 54 pivotal studies. Of these, 41 (76%) were randomised controlled trials and 13 (24%) were either non-randomised studies or single arm studies. 39/41 randomised controlled trials had available publications and were included in our study. Only 10 randomised controlled trials (26%) measured overall survival as either a primary or coprimary endpoint, with the remaining trials evaluating surrogate measures such as progression free survival and response rates. Overall, 19 randomised controlled trials (49%) were judged to be at high risk of bias for their primary outcome. Concerns about missing outcome data (n=10) and measurement of the outcome (n=7) were the most common domains leading to high risk of bias judgments. Fewer randomised controlled trials that evaluated overall survival as the primary endpoint were at high risk of bias than those that evaluated surrogate efficacy endpoints (2/10 (20%) v 16/29 (55%), respectively). When information available in regulatory documents and the scientific literature was considered separately, overall risk of bias judgments differed for eight randomised controlled trials (21%), which reflects reporting inadequacies in both sources of information. Regulators identified additional deficits beyond the domains captured in risk of bias assessments for 10 drugs (31%). These deficits included magnitude of clinical benefit, inappropriate comparators, and non-preferred study endpoints, which were not disclosed as limitations in scientific publications.
Conclusions: Most pivotal studies forming the basis of EMA approval of new cancer drugs between 2014 and 2016 were randomised controlled trials. However, almost half of these were judged to be at high risk of bias based on their design, conduct, or analysis, some of which might be unavoidable because of the complexity of cancer trials. Regulatory documents and the scientific literature had gaps in their reporting. Journal publications did not acknowledge the key limitations of the available evidence identified in regulatory documents.
(Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
التعليقات: Comment in: BMJ. 2019 Oct 15;367:l6017. (PMID: 31615783)
Comment in: Future Oncol. 2020 Jan;16(3):4419-4423. (PMID: 31823651)
Comment in: BMJ. 2019 Sep 18;366:l5399. (PMID: 32027600)
References: Lancet. 2002 Feb 16;359(9306):614-8. (PMID: 11867132)
BMJ. 2004 Jan 3;328(7430):22-4. (PMID: 14703540)
PLoS Med. 2006 Oct;3(10):e425. (PMID: 17076559)
Int J Epidemiol. 2007 Jun;36(3):654-63. (PMID: 17440024)
Ann Intern Med. 2007 Jun 19;146(12):882-7. (PMID: 17577008)
J Clin Oncol. 2008 Jan 1;26(1):6-8. (PMID: 18165630)
BMJ. 2008 Mar 15;336(7644):601-5. (PMID: 18316340)
J Clin Oncol. 2008 Nov 20;26(33):5458-64. (PMID: 18955452)
J Clin Oncol. 2009 Jun 10;27(17):2874-80. (PMID: 19414672)
BMJ. 2009 Sep 07;339:b3244. (PMID: 19736281)
J Clin Oncol. 2009 Dec 10;27(35):5958-64. (PMID: 19826121)
BMJ. 2010 Mar 23;340:c869. (PMID: 20332511)
BMJ. 2011 May 25;342:d2291. (PMID: 21613341)
Eur J Cancer. 2011 Aug;47(12):1759-62. (PMID: 21641204)
JAMA. 2011 Jun 8;305(22):2320-6. (PMID: 21642684)
BMJ. 2011 Jul 05;343:d4244. (PMID: 21729988)
BMJ. 2011 Sep 06;343:d4849. (PMID: 21896610)
Cochrane Database Syst Rev. 2011 Sep 07;(9):MR000025. (PMID: 21901737)
BMJ. 2011 Oct 18;343:d5928. (PMID: 22008217)
Eur J Cancer. 2012 Feb;48(3):385-8. (PMID: 22115991)
BMJ. 2012 Jan 03;344:d8141. (PMID: 22214759)
J Clin Oncol. 2012 Apr 1;30(10):1030-3. (PMID: 22370321)
BMJ. 2012 Feb 27;344:e1119. (PMID: 22371859)
J Clin Epidemiol. 2012 Jun;65(6):602-9. (PMID: 22424985)
Ann Intern Med. 2012 Sep 18;157(6):429-38. (PMID: 22945832)
N Engl J Med. 2012 Nov;367(18):1694-703. (PMID: 23020132)
Syst Rev. 2012 Nov 29;1:60. (PMID: 23194585)
Ann Oncol. 2013 May;24(5):1238-44. (PMID: 23303339)
BMJ. 2013 Jan 21;346:e8668. (PMID: 23338004)
BMJ. 2013 Apr 22;346:f1798. (PMID: 23610376)
BMJ. 2013 Apr 23;346:f2231. (PMID: 23613540)
Clin Cancer Res. 2013 May 15;19(10):2613-20. (PMID: 23669421)
PLoS Med. 2013 Oct;10(10):e1001526. (PMID: 24115912)
J Clin Oncol. 2014 Jan 10;32(2):83-9. (PMID: 24323037)
Ann Oncol. 2014 Jan;25(1):265-9. (PMID: 24356637)
Int J Epidemiol. 2014 Jun;43(3):937-48. (PMID: 24448109)
JAMA. 2014 Jan 22-29;311(4):368-77. (PMID: 24449315)
J Clin Epidemiol. 2014 Oct;67(10):1059-69. (PMID: 24973822)
JAMA Otolaryngol Head Neck Surg. 2014 Dec;140(12):1225-36. (PMID: 25068501)
Value Health. 2014 Jul;17(5):634-41. (PMID: 25128058)
BMJ Open. 2014 Sep 30;4(9):e005253. (PMID: 25270852)
Ann Oncol. 2015 Jan;26(1):231-7. (PMID: 25355720)
BMJ. 2015 Feb 26;350:h796. (PMID: 25722024)
Eur J Cancer. 2015 Apr;51(6):721-4. (PMID: 25728257)
BMJ. 2015 Mar 24;350:h809. (PMID: 25804210)
BMJ. 2015 Apr 23;350:h2068. (PMID: 25908437)
Lancet. 2015 Apr 18;385(9977):1502-3. (PMID: 25933270)
BMJ. 2015 May 27;350:h2445. (PMID: 26016488)
Res Synth Methods. 2014 Mar;5(1):79-85. (PMID: 26054027)
JAMA Intern Med. 2015 Aug;175(8):1389-98. (PMID: 26098871)
J Clin Epidemiol. 2015 Sep;68(9):1036-45. (PMID: 26227423)
Eur J Cancer. 2015 Nov;51(16):2269-71. (PMID: 26259493)
Eur J Intern Med. 2015 Oct;26(8):572-84. (PMID: 26342723)
BMJ. 2015 Oct 23;351:h5542. (PMID: 26496934)
JAMA Intern Med. 2015 Dec;175(12):1992-4. (PMID: 26502403)
Eur J Cancer. 2016 Jul;61:29-35. (PMID: 27151552)
PLoS Med. 2016 May 24;13(5):e1002028. (PMID: 27218655)
JAMA Oncol. 2016 Sep 1;2(9):1238-40. (PMID: 27281466)
BMJ Open. 2016 Jun 30;6(6):e011666. (PMID: 27363818)
PLoS One. 2016 Jul 11;11(7):e0159267. (PMID: 27398997)
J Clin Epidemiol. 2017 Jan;81:42-50. (PMID: 27555081)
Support Care Cancer. 2017 Jan;25(1):237-244. (PMID: 27619389)
Ann Oncol. 2017 Jan 1;28(1):157-162. (PMID: 27742650)
Epidemiology. 2017 Jan;28(1):54-59. (PMID: 27748683)
BMJ. 2016 Nov 17;355:i5663. (PMID: 27856428)
Lancet Oncol. 2016 Dec;17(12):e560-e567. (PMID: 27924754)
BMJ. 2017 Apr 27;357:j1991. (PMID: 28450290)
Ann Oncol. 2017 Aug 1;28(8):1738-1750. (PMID: 28453615)
BMJ. 2017 May 2;357:j2062. (PMID: 28465401)
New Bioeth. 2017 Apr;23(1):95-104. (PMID: 28517989)
Am J Health Syst Pharm. 2017 Aug 1;74(15):1158-1173. (PMID: 28533252)
Lancet Oncol. 2017 Jul;18(7):887-894. (PMID: 28583794)
Milbank Q. 2017 Jun;95(2):261-290. (PMID: 28589600)
BMJ. 2017 Jun 8;357:j2490. (PMID: 28596181)
JAMA. 2017 Aug 15;318(7):626-636. (PMID: 28810023)
BMJ. 2017 Oct 4;359:j4530. (PMID: 28978555)
Clin Pharmacol Ther. 2018 Jul;104(1):169-177. (PMID: 29023675)
Nat Rev Drug Discov. 2018 Feb;17(2):81-85. (PMID: 29348678)
JAMA. 2018 Jan 23;319(4):404-406. (PMID: 29362786)
Nat Rev Drug Discov. 2018 Feb 1;17(2):86. (PMID: 29386604)
BMJ. 2018 May 25;361:k1452. (PMID: 29802130)
Support Care Cancer. 2018 Nov;26(11):3941-3949. (PMID: 29845422)
Syst Rev. 2018 Aug 8;7(1):117. (PMID: 30089508)
BMJ Open. 2018 Sep 10;8(9):e017240. (PMID: 30206071)
JAMA Oncol. 2018 Nov 1;4(11):1610-1611. (PMID: 30267037)
JAMA Intern Med. 2018 Dec 1;178(12):1586-1596. (PMID: 30285081)
Int J Cancer. 2019 Apr 1;144(7):1746-1751. (PMID: 30374970)
BMJ. 2018 Nov 1;363:k4383. (PMID: 30385466)
Eur J Cancer. 2019 Jan;106:196-211. (PMID: 30528804)
Soc Sci Med. 2019 Feb;222:76-83. (PMID: 30605802)
JAMA Intern Med. 2019 May 1;179(5):642-647. (PMID: 30933235)
Lancet. 2019 Jul 27;394(10195):281-283. (PMID: 31354129)
Value Health. 2019 Aug;22(8):884-890. (PMID: 31426929)
BMJ. 2019 Aug 28;366:l4898. (PMID: 31462531)
JAMA. 1995 Feb 1;273(5):408-12. (PMID: 7823387)
معلومات مُعتمدة: MR/K025643/1 United Kingdom MRC_ Medical Research Council
المشرفين على المادة: 0 (Antineoplastic Agents)
تواريخ الأحداث: Date Created: 20190920 Date Completed: 20190926 Latest Revision: 20210110
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6749182
DOI: 10.1136/bmj.l5221
PMID: 31533922
قاعدة البيانات: MEDLINE
الوصف
تدمد:1756-1833
DOI:10.1136/bmj.l5221