Factors associated with failure to publish large randomized trials presented at an oncology meeting. The end-of-study patient survey: methods influencing response rate in the AVID Trial. A cohort study of summary reports of controlled trials. An example of European multicenter trials: multispectral analysis of clozapine.
Large clinical trials are the criterion standard for making treatment decisions, and nonpublication of the results of such trials can lead to bias in the literature and contribute to inappropriate medical decisions.
                To determine the rate of full publication of large randomized trials presented at annual meetings of the American Society of Clinical Oncology (ASCO), quantify bias against publishing nonsignificant results, and identify factors associated with time to publication.
                Survey of 510 abstracts from large (sample size, > or =200), phase 3, randomized controlled trials presented at ASCO meetings between 1989 and 1998. Trial results were classified as significant (P< or =.05 for the primary outcome measure) or nonsignificant (P>.05 or not reported), and the type of presentation and sponsorship were identified. Subsequent full publication was identified using a search of MEDLINE and EMBASE, completed November 1, 2001; the search was updated in November 2002, using the Cochrane Register of Controlled Trials. Authors were contacted if the searches did not find evidence of publication.
                Publication rate at 5 years; time from presentation to full publication.
                Of 510 randomized trials, 26% were not published in full within 5 years after presentation at the meeting. Eighty-one percent of the studies with significant results had been published by this time compared with 68% of the studies with nonsignificant results (P<.001). Studies with oral or plenary presentation were published sooner than those not presented (P =.002), and studies with pharmaceutical sponsorship were published sooner than studies with cooperative group sponsorship or studies for which sponsorship was not specified (P =.02). These factors remained significant in a multivariable model. The most frequent reason cited by authors for not publishing was lack of time, funds, or other resources.
                A substantial number of large phase 3 trials presented at an international oncology meeting remain unpublished 5 years after presentation. Bias against publishing nonsignificant results is a problem even for large randomized trials. Nonpublication breaks the contract that investigators make with trial participants, funding agencies, and ethics boards. Patient surveys are commonly distributed at the end of a multicenter clinical trial. This Antiarrhythmics Versus Implantable Defibrillators (AVID) substudy prospectively explored the relationship between methods used in distributing a survey and the quantity of responses received. AVID was a multicenter, randomized trial comparing survival in arrhythmia patients treated with antiarrhythmic drugs versus implantable defibrillators. At study termination, a patient satisfaction survey was mailed to the 664 surviving participants. Questions included reasons for study participation, study benefits and problems and quality of care. Survey mailings were stratified by four factors in a 2x2x2x2 factorial design: delivery mode (overnight vs. regular mail), certificate of appreciation, timing of administration ("early" vs. "late") and cover letter signed by a physician versus coordinator. Patients were randomly assigned to received one of 16 combinations of these four factors. Clinical characteristics and response rates were evaluated. Patients were more likely to return surveys delivered by overnight mail (75% vs. 68%, p=0.04), with no certificate of appreciation enclosed (75% vs. 68%, p=0.05) and administered close to the time of study closeout (79% vs. 72%, p=0.085). Compared to the 184 nonrespondents, the 456 (71%) respondents were older, Caucasian, lived with others, were high school graduates and less likely to have Medicare/Medicaid or HMO insurance (p<0.03). Physician recommendation was the most common reason cited for trial participation. Main benefits included increased knowledge of their medical condition and improved health. Reported problems included parking, transportation and excess clinic wait time. This randomized study demonstrated that methods of patient survey distribution affect the survey return rate. Additional studies should explore mechanisms for maximizing return rates.
                Copyright 2002 Elsevier Science Inc. Substantial numbers of clinical trials continue to be reported only in summary reports that present insufficient methodological details to permit informed judgments about the likely validity of the conclusions. Using a cohort of 176 controlled trials reported in summary form, we tested the hypotheses that they would be more likely to be followed by full reports if, on the basis of the information provided in the summary report, (1) the trial was judged to be methodologically sound, (2) the results favored the test treatment, and (3) the sample size was relatively large. The results of univariate and multivariate analyses provided support for only the third of these hypotheses. Investigators, as well as those who fund and sanction the conduct of clinical research, should make greater efforts to ensure that clinical trials are reported properly. nan
The number of trials and participants is insufficient to draw final conclusions. A large multicenter study with adequate power is needed.