Editorial policies for clinical trials and the continued changes in medical journalism.

The importance of randomized clinical trials is acknowledged by most physicians, professional organizations, and federal agencies. Clinical trials influence practice and are at the pinnacle of the evidence pyramid, either alone or as part of meta-analyses. However, many threats to the validity and scientific integrity of clinical trials can occur in their design, implementation, analysis, and reporting. Examples include modifications in primary and secondary outcomes or analytic approaches after the trial begins or after initial examination of data; manipulation and falsification of data; incomplete reporting of all available trial outcomes and selective reporting of important serious adverse events; and failure to report the results of trials with negative or unfavorable results. Currentbestpractice toensure scientific validity in thedesign and conduct of clinical trials includes prespecification of the trial protocol, an associated statistical analytic plan, careful documentation of any changes in the protocol, and oversight by institutional reviewboards (IRBs) anddata and safety monitoring committees. Best practice for reporting of clinical trials includes emphasis on the primary outcomes; distinguishing between secondary outcomes and post hoc analyses; careful attention to statistical issues, such as maintaining fidelity to the original statistical analysis plan and appropriate treatment ofmissing data; complete reporting of adverse events; and balanced, objective interpretation of the study findings. Many changes have occurred in the reporting of clinical trials over the last decade and have served to address many of these threats to validity. Trial registration,mandated since 2005 by the International Committee of Medical Journal Editors,1 has reduced the likelihood of suppressed trials and hashelped improve the fidelity of clinical trial analysis and reporting, such as reducing selective or altered reporting ofmajor outcomes. TheCONSORTstatementwas released in 1996,2 revised in 20013 and2010,4with extensions that focusonnoninferiority trials in 20065 and 2012,6 cluster randomized trials (2012),7 and patient-reported outcomes (2013),8 and has been widely adopted by most medical journals as a mechanism to improve and standardize reporting of clinical trials. In addition,morewidespread availability anddetailed reviewof trial protocols and statistical analytic planshashelped clarify the intentionof investigators at the time studies aredesigned, andalongwithgradual increases in theamountofdata sharing, have facilitated the ability of reviewers and journal editors toassess the scientific validityof studies.Following the approval of new drugs, the US Food andDrug Administration (FDA),which requires submissionof completedata fromtrials of products under consideration for approval, is making trial datamore readilyandeasilyaccessible (Erica Jefferson,deputy director of the FDA office of public affairs, written communication, May 16, 2013). Likewise, the European Medicines Agency announced plans to provide access to all clinical trial data sets submitted by industry in applications for newproduct registration, andsomepharmaceutical companieshaveannounced plans to make data available to appropriate groups upon request. Collectively these changes have led to a substantial improvement in reporting, assessment, and transparency of clinical trials. In 2005 JAMA adopted andmodified anumber of policies regardingconflictsof interest, financial aspectsof research,and the role of sponsors in funded research.9 These policies— which includedarequirement for independentstatisticalanalysis by an academic biostatistician for industry-sponsored and industry-analyzedstudies—weredevelopedduringatimewhen several high-profile trials had evidence of problemswithdata integrity, inappropriately conducted statistical analyses, and incomplete reporting of major findings. Over time some of thesepolicieshavebeenmodifiedandstrengthened10buthave been perceived by some in academia and industry as creating barriers topublicationof important trial results.Moreover,over the past 2 years, our experience has been that the conduct of additional analyses by independent academic biostatisticians generally did not result in meaningful changes in the study results. Accordingly,we are once againmodifying one of the policies. JAMAwill evaluate and consider for publication clinical trials that are analyzed by statisticians employed by or contracted by the study sponsor, without requiring independent statistical analysis by an academic biostatistician. Advances over thepastdecade in standardsof clinical trial reporting, enhanced understanding of the threats to validity of clinical research, increasingdata transparency, andour experience support the change in policy. We will continue to require submission of a copy of the trial protocol and statistical analytic plan with all amendments, and we will require trials to be appropriately registered in an approved publicly accessible database. Any changes to the protocol, analysis plan, or trial registration that occurred after the trial began need to be explained in detail and justified with appropriate documentation. JAMA editorial review will continue to include close examination of these documents for discrepancies with the submitted manuscript and diligent evaluation and scrutiny of all scienOpinion