The use of interim data and Data Monitoring Committee recommendations in randomized controlled trial reports: frequency, implications and potential sources of bias
Open Access
- 20 March 2008
- journal article
- review article
- Published by Springer Science and Business Media LLC in BMC Medical Research Methodology
- Vol. 8 (1), 12
- https://doi.org/10.1186/1471-2288-8-12
Abstract
Interim analysis of accumulating trial data is important to protect participant safety during randomized controlled trials (RCTs). Data Monitoring Committees (DMCs) often undertake such analyses, but their widening role may lead to extended use of interim analysis or recommendations that could potentially bias trial results. Systematic search of eight major publications: Annals of Internal Medicine, BMJ, Circulation, CID, JAMA, JCO, Lancet and NEJM, including all randomised controlled trials (RCTs) between June 2000 and May 2005 to identify RCTs that reported use of interim analysis, with or without DMC involvement. Recommendations made by the DMC or based on interim analysis were identified and potential sources of bias assessed. Independent double data extraction was performed on all included trials. We identified 1772 RCTs, of which 470 (27%; 470/1772) reported the use of a DMC and a further 116 (7%; 116/1772) trials reported some form of interim analysis without explicit mention of a DMC. There were 28 trials (24 with a formal DMC), randomizing a total of 79396 participants, identified as recommending changes to the trial that may have lead to biased results. In most of these, some form of sample size re-estimation was recommended with four trials also reporting changes to trial endpoints. The review relied on information reported in the primary publications and methods papers relating to the trials, higher rates of use may have occurred but not been reported. The reported use of interim analysis and DMCs in clinical trials has been increasing in recent years. It is reassuring that in most cases recommendations were made in the interest of participant safety. However, in practice, recommendations that may lead to potentially biased trial results are being made.Keywords
This publication has 36 references indexed in Scilit:
- Full publication of results initially presented in abstractsCochrane Database of Systematic Reviews, 2007
- Full publication of results initially presented in abstractsPublished by Wiley ,2005
- Randomized Trial of Amifostine in Locally Advanced Non–Small-Cell Lung Cancer Patients Receiving Chemotherapy and Hyperfractionated Radiation: Radiation Therapy Oncology Group Trial 98-01Journal of Clinical Oncology, 2005
- Empirical Evidence for Selective Reporting of Outcomes in Randomized TrialsJAMA, 2004
- Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trialThe Lancet, 2004
- Efficacy and Safety of Tenecteplase in Combination With the Low-Molecular-Weight Heparin Enoxaparin or Unfractionated Heparin in the Prehospital SettingCirculation, 2003
- Randomized Study to Evaluate the Use of High-Dose Therapy as Part of Primary Treatment for “Aggressive” LymphomaJournal of Clinical Oncology, 2002
- Sample size re‐estimation – journey for a decadeStatistics in Medicine, 2001
- Glycine antagonist (gavestinel) in neuroprotection (GAIN International) in patients with acute stroke: a randomised controlled trialThe Lancet, 2000
- Importance of trends in the interpretation of an overall odds ratio in the meta‐analysis of clinical trialsStatistics in Medicine, 1994