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. Factors associated with breast cancer clinical trials participation and enrollment at a large academic medical center. Comparison of registered and published primary outcomes in randomized controlled trials. Recruitment of patients to cooperative group clinical trials. Outcome reporting among drug trials registered in ClinicalTrials.gov. A randomised trial of the effects of an additional communication strategy on recruitment into a large-scale, multi-centre trial.
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 practice patterns of medical oncologists at a large National Cancer Institute Comprehensive Cancer Center in Detroit, MI were evaluated to better understand factors associated with accrual to breast cancer clinical trials.
                From 1996 to 1997, physicians completed surveys on 319 of 344 newly evaluated female breast cancer patients. The 19-item survey included clinical data, whether patients were offered clinical trial (CT) participation and enrollment, and when applicable, reasons why they were not. Multivariate analyses using logistic regression were performed to evaluate predictors of an offer and enrollment.
                The patients were 57% white, 32% black, and 11% other/unknown race. One hundred six (33%) were offered participation and 36 (34%) were enrolled. In multivariate analysis, CTs were less likely offered to older women (mean age, 52 years for those offered v 57 years for those not offered; P =.0005) and black women (21% of blacks offered v 42% of whites; P =.0009). Women with stage 1 disease, poor performance status, and those who were previously diagnosed were also less likely to be offered trials. None of these factors were significant predictors of enrollment. Women were not offered trials because of ineligibility (57%), lack of available trials (41%), and noncompliance (2%). Reasons for failed enrollment included patient refusal (88%) and failed eligibility (12%).
                It is important for cooperative groups to design studies that will accommodate a broader spectrum of patients. Further work is needed to assess ways to improve communication about breast cancer CT participation to all eligible women. As of 2005, the International Committee of Medical Journal Editors required investigators to register their trials prior to participant enrollment as a precondition for publishing the trial's findings in member journals.
                To assess the proportion of registered trials with results recently published in journals with high impact factors; to compare the primary outcomes specified in trial registries with those reported in the published articles; and to determine whether primary outcome reporting bias favored significant outcomes.
                MEDLINE via PubMed was searched for reports of randomized controlled trials (RCTs) in 3 medical areas (cardiology, rheumatology, and gastroenterology) indexed in 2008 in the 10 general medical journals and specialty journals with the highest impact factors.
                For each included article, we obtained the trial registration information using a standardized data extraction form.
                Of the 323 included trials, 147 (45.5%) were adequately registered (ie, registered before the end of the trial, with the primary outcome clearly specified). Trial registration was lacking for 89 published reports (27.6%), 45 trials (13.9%) were registered after the completion of the study, 39 (12%) were registered with no or an unclear description of the primary outcome, and 3 (0.9%) were registered after the completion of the study and had an unclear description of the primary outcome. Among articles with trials adequately registered, 31% (46 of 147) showed some evidence of discrepancies between the outcomes registered and the outcomes published. The influence of these discrepancies could be assessed in only half of them and in these statistically significant results were favored in 82.6% (19 of 23).
                Comparison of the primary outcomes of RCTs registered with their subsequent publication indicated that selective outcome reporting is prevalent. One of the prerequisites for a successful clinical trial is the accrual of a sufficient number of patients for study. Because the sample-size requirements for a randomized clinical trial can rarely be met by a single institution in a short period of time, cooperative groups have taken in a major role in conducting clinical trials. In this paper, the recruitment of patients at our institution to a lung cancer clinical trial is evaluated. A total of 653 lung cancer cases were reviewed. Of the 77 cases which were eligible for the trial, 41 were accessioned. The reasons why eligible patients were not accessioned to the trial are discussed. Clinical trial registries are in widespread use to promote transparency around trials and their results.
                To describe characteristics of drug trials listed in ClinicalTrials.gov and examine whether the funding source of these trials is associated with favorable published outcomes.
                An observational study of safety and efficacy trials for anticholesteremics, antidepressants, antipsychotics, proton-pump inhibitors, and vasodilators conducted between 2000 and 2006.
                ClinicalTrials.gov, a Web-based registry of clinical trials launched in 1999.
                Publications resulting from the trials for the 5 drug categories of interest were identified, and data were abstracted on the trial record and publication, including timing of registration, elements of the study design, funding source, publication date, and study outcomes. Assessments were based on the primary funding categories of industry, government agencies, and nonprofit or nonfederal organizations.
                Among 546 drug trials, 346 (63%) were primarily funded by industry, 74 (14%) by government sources, and 126 (23%) by nonprofit or nonfederal organizations. Trials funded by industry were more likely to be phase 3 or 4 trials (88.7%; P < 0.001 across groups), to use an active comparator in controlled trials (36.8%; P = 0.010 across groups), to be multicenter (89.0%; P < 0.001 across groups), and to enroll more participants (median sample size, 306 participants; P < 0.001 across groups). Overall, 362 (66.3%) trials had published results. Industry-funded trials reported positive outcomes in 85.4% of publications, compared with 50.0% for government-funded trials and 71.9% for nonprofit or nonfederal organization-funded trials (P < 0.001). Trials funded by nonprofit or nonfederal sources with industry contributions were also more likely to report positive outcomes than those without industry funding (85.0% vs. 61.2%; P = 0.013). Rates of trial publication within 24 months of study completion ranged from 32.4% among industry-funded trials to 56.2% among nonprofit or nonfederal organization-funded trials without industry contributions (P = 0.005 across groups).
                The publication status of a trial could not always be confirmed, which could result in misclassification. Additional information on study protocols and comprehensive trial results were not available to further explore underlying factors for the association between funding source and outcome reporting.
                In this sample of registered drug trials, those funded by industry were less likely to be published within 2 years of study completion and were more likely to report positive outcomes than were trials funded by other sources.
                National Library of Medicine and National Institute of Child Health and Human Development, National Institutes of Health. Timely participant recruitment remains a significant challenge for most clinical trials. We evaluated the effects on participant recruitment of communication between the central trial coordinators and the clinical sites in the setting of a large international multi-centre clinical trial. The effects of communication were determined in a single-blind randomised controlled trial involving 167 clinical sites in 19 countries. Clinical sites were randomised to either additional or usual communication strategies - the additional communication group received a communication package based on additional, individually-tailored feedback about recruitment, in addition to the usual correspondence from the central trial coordinators that was provided to the control group. The two study outcomes were the median time to half randomisation target and the median total number of participants randomised per clinical site. Eighty-five clinical centres were randomised to receive additional communication and 82 to receive usual communication. At the conclusion of recruitment, there was no significant difference in the median number of participants randomised per centre between the additional and usual groups (37.5 vs. 37.0, p=0.68). The median time to half randomisation target was lower in the additional communication group compared to the usual group, however this difference did not achieve conventional levels of statistical significance (4.4 months vs. 5.8 months, p=0.08). The findings suggest that the additional communication strategy may be of some incremental benefit in helping sites achieve recruitment targets sooner.
The number of trials and participants is insufficient to draw final conclusions. A large multicenter study with adequate power is needed.