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The authors declare that they have no competing interests.
MD provided the inception of the research idea and drafted the protocol. MD, LF and AA conducted the feasibility study. IH, AA, MD and LF contributed to the data collection and analysis. MD, LF and AA performed the quality control. AA and MD wrote the first draft of the manuscript. SJ reviewed and contributed to the writing of the paper and provided support as required. All authors revised the manuscript and approved the final version.
The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health or the University of Sheffield.
Adaptive designs have the potential to improve efficiency in the evaluation of new medical treatments in comparison to traditional fixed sample size designs. However, they are still not widely used in practice in clinical research. Little research has been conducted to investigate what adaptive designs are being undertaken. This review highlights the current state of registered adaptive designs and their characteristics. The review looked at phase II, II/III and III trials registered on ClinicalTrials.gov from 29 February 2000 to 1 June 2014, supplemented with trials from the National Institute for Health Research register and known adaptive trials. A range of adaptive design search terms were applied to the trials extracted from each database. Characteristics of the adaptive designs were then recorded including funder, therapeutic area and type of adaptation. The results in the paper suggest that the use of adaptive designs has increased. They seem to be most often used in phase II trials and in oncology. In phase III trials, the most popular form of adaptation is the group sequential design. The review failed to capture all trials with adaptive designs, which suggests that the reporting of adaptive designs, such as in clinical trials registers, needs much improving. We recommend that clinical trial registers should contain sections dedicated to the type and scope of the adaptation and that the term ‘adaptive design’ should be included in the trial title or at least in the brief summary or design sections.
Additional file 1 Search terms. PDF with a table of the final selection of search terms used in the review. (PDF 6.19 kb)13063_2016_1273_MOESM1_ESM.pdf
Additional file 2 Table of summary statistics. PDF containing a table of summary statistics by phase and funder type. Counts and percentages are presented for categorical variables whilst medians and interquartile ranges are presented for continuous variables. (PDF 19.5 kb)13063_2016_1273_MOESM2_ESM.pdf
Additional file 3 Case studies. XLSX file containing a list of the trials used in the review. Trial number, title and URL are provided. (XLSX 35.2 kb)13063_2016_1273_MOESM3_ESM.xlsx
Millard WB. The gold standard’s flexible alloy: adaptive designs on the advance. Ann Emerg Med. 2012; 60(2):22–7. CrossRef
Coffey CS, Kairalla JA. Adaptive clinical trials. Drugs R&D. 2008; 9(4):229–42. CrossRef
Gaydos B, Anderson KM, Berry D, Burnham N, Chuang-Stein C, Dudinak J, et al.Good practices for adaptive clinical trials in pharmaceutical product development. Ther Innov Regul Sci. 2009; 43(5):539–56. CrossRef
Quinlan JA, Krams M. Implementing adaptive designs: logistical and operational considerations. Drug Inf J. 2006; 40(4):437–44.
FDA Draft Guidance. Adaptive design clinical trials for drugs and biologics. Biotechnol Law Rep. 2010; 29(2):173. CrossRef
Morgan CC, Huyck S, Jenkins M, Chen L, Bedding A, Coffey CS, et al.Adaptive design: results of 2012 survey on perception and use. Ther Innov Regul Sci. 2014; 48(4):473–81. CrossRef
ClinicalTrials.gov: a service of the US National Institutes of Health. https://clinicaltrials.gov/. Accessed May 2015.
World Health Organization. International clinical trials registry platform search portal. http://apps.who.int/trialsearch/. Accessed May 2014.
NIHR evaluation, trials and studies project portfolio. http://www.nets.nihr.ac.uk/projects?collection=netscc&meta_P_sand=Project. Accessed May 2015.
Chow SC, Chang M. Adaptive design methods in clinical trials. Boca Raton: CRC Press; 2011.
Hopewell S, Loudon K, Clarke MJ, Oxman AD, Dickersin K. Publication bias in clinical trials due to statistical significance or direction of trial results. The Cochrane Library. 2009.
Lin M, Lee S, Zhen B, Scott J, Horne A, Solomon G, et al.CBER’s experience with adaptive design clinical trials. Ther Innov Regul Sci. 2016; 50(2):195–203. CrossRef
Stevely A, Dimairo M, Todd S, Julious SA, Nicholl J, Hind D, et al.An investigation of the shortcomings of the CONSORT 2010 statement for the reporting of group sequential randomised controlled trials: a methodological systematic review. PloS ONE. 2015; 10(11):0141104. CrossRef
James ND, Sydes MR, Mason MD, Clarke NW, Anderson J, Dearnaley DP, et al.Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: first results from the STAMPEDE multiarm, multistage, randomised controlled trial. Lancet Oncol. 2012; 13(5):549–58. CrossRefPubMedPubMedCentral
Lan KG, DeMets DL. Discrete sequential boundaries for clinical trials. Biometrika. 1983; 70(3):659–63. CrossRef
Collinson FJ, Gregory WM, McCabe C, Howard H, Lowe C, Potrata B, et al.The STAR trial protocol: a randomised multi-stage phase II/III study of sunitinib comparing temporary cessation with allowing continuation, at the time of maximal radiological response, in the first-line treatment of locally advanced/metastatic renal cancer. BMC Cancer. 2012; 12(1):598. CrossRefPubMedPubMedCentral
- Adaptive designs undertaken in clinical research: a review of registered clinical trials
Steven A. Julious
- BioMed Central