Comparison of Availability of Trial Results in ClinicalTrials.gov and PubMed by Data Source and Funder Type.

This study examines the dissemination of trial results by data source (ie, ClinicalTrials.gov and PubMed) and funder type (ie, industry and nonindustry).

Independent data monitoring committees: preparing a path for the future.

Independent data monitoring committees (IDMCs) were introduced to monitor patient safety and study conduct in randomized clinical trials (RCTs), but certain challenges regarding the utilization of IDMCs have developed. First, the roles and responsibilities of IDMCs are expanding, perhaps due to increasing trial complexity and heterogeneity regarding medical, ethical, legal, regulatory, and financial issues. Second, no standard for IDMC operating procedures exists, and there is uncertainty about who should determine standards and whether standards should vary with trial size and design. Third, considerable variability in communication pathways exist across IDMC interfaces with regulatory agencies, academic coordinating centers, and sponsors. Finally, there has been a substantial increase in the number of RCTs using IDMCs, yet there is no set of qualifications to help guide the training and development of the next generation of IDMC members. Recently, an expert panel of representatives from government, industry, and academia assembled at the Duke Clinical Research Institute to address these challenges and to develop recommendations for the future utilization of IDMCs in RCTs.

Characteristics of clinical trials registered in ClinicalTrials.gov, 2007-2010.

CONTEXT: Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials portfolio. OBJECTIVE: To examine fundamental characteristics of interventional clinical trials registered in the ClinicalTrials.gov database. METHODS: A data set comprising 96,346 clinical studies from ClinicalTrials.gov was downloaded on September 27, 2010, and entered into a relational database to analyze aggregate data. Interventional trials were identified and analyses were focused on 3 clinical specialties-cardiovascular, mental health, and oncology-that together encompass the largest number of disability-adjusted life-years lost in the United States. MAIN OUTCOME MEASURES: Characteristics of registered clinical trials as reported data elements in the trial registry; how those characteristics have changed over time; differences in characteristics as a function of clinical specialty; and factors associated with use of randomization, blinding, and data monitoring committees (DMCs). RESULTS: The number of registered interventional clinical trials increased from 28,881 (October 2004-September 2007) to 40,970 (October 2007-September 2010), and the number of missing data elements has generally declined. Most interventional trials registered between 2007 and 2010 were small, with 62% enrolling 100 or fewer participants. Many clinical trials were single-center (66%; 24,788/37,520) and funded by organizations other than industry or the National Institutes of Health (NIH) (47%; 17,592/37,520). Heterogeneity in the reported methods by clinical specialty; sponsor type; and the reported use of DMCs, randomization, and blinding was evident. For example, reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials (adjusted odds ratio [OR], 0.11; 95% CI, 0.09-0.14), earlier-phase vs phase 3 trials (adjusted OR, 0.83; 95% CI, 0.76-0.91), and mental health trials vs those in the other 2 specialties. In similar comparisons, randomization and blinding were less frequently reported in earlier-phase, oncology, and device trials. CONCLUSION: Clinical trials registered in ClinicalTrials.gov are dominated by small trials and contain significant heterogeneity in methodological approaches, including reported use of randomization, blinding, and DMCs.

Publication of NIH funded trials registered in ClinicalTrials.gov: cross sectional analysis.

OBJECTIVE: To review patterns of publication of clinical trials funded by US National Institutes of Health (NIH) in peer reviewed biomedical journals indexed by Medline. DESIGN: Cross sectional analysis. SETTING: Clinical trials funded by NIH and registered within ClinicalTrials.gov (clinicaltrials.gov), a trial registry and results database maintained by the US National Library of Medicine, after 30 September 2005 and updated as having been completed by 31 December 2008, allowing at least 30 months for publication after completion of the trial. MAIN OUTCOME MEASURES: Publication and time to publication in the biomedical literature, as determined through Medline searches, the last of which was performed in June 2011. RESULTS: Among 635 clinical trials completed by 31 December 2008, 294 (46%) were published in a peer reviewed biomedical journal, indexed by Medline, within 30 months of trial completion. The median period of follow-up after trial completion was 51 months (25th-75th centiles 40-68 months), and 432 (68%) were published overall. Among published trials, the median time to publication was 23 months (14-36 months). Trials completed in either 2007 or 2008 were more likely to be published within 30 months of study completion compared with trials completed before 2007 (54% (196/366) v 36% (98/269); P<0.001). CONCLUSIONS: Despite recent improvement in timely publication, fewer than half of trials funded by NIH are published in a peer reviewed biomedical journal indexed by Medline within 30 months of trial completion. Moreover, after a median of 51 months after trial completion, a third of trials remained unpublished.

Trial Registration at ClinicalTrials.gov between May and October 2005.

BACKGROUND: Clinical trial registration allows interested parties to obtain information about ongoing and completed trials, but there are few data indicating the quality of the information provided during the registration process. We used information in the publicly available ClinicalTrials.gov database to describe patterns of trial registration before and after the implementation by journal editors of a new policy requiring registration as a prerequisite for publication. METHODS: We reviewed ClinicalTrials.gov records to determine patterns of completion of the "Intervention Name" and "Primary Outcome Measure" data fields for trials registered on May 20 and October 11, 2005, and for trials registered during the interval between these two dates, inclusively. RESULTS: During the interval studied, the number of registrations in ClinicalTrials.gov increased by 73 percent from 13,153 to 22,714. The percentage of interventional trials registered by industry with nonspecific Intervention Name entries (attributable to four drug companies) decreased from 10 percent to 2 percent; all other industry and nonindustry records contained specific entries in this field. Of the 2670 studies registered by industry between the two dates, 76 percent provided information in the Primary Outcome Measure field, although these entries varied markedly in their degree of specificity. In the remaining 24 percent of the records, this field was blank. CONCLUSIONS: During the summer of 2005, there were large increases in the number of clinical trial registrations. Overall, the data contained in records were more complete in October than they were in May, but there still is room for substantial improvement.

Challenges in systematic reviews of diagnostic technologies.

Diagnostic tests are critical components of effective health care. They help determine treatments that are most beneficial for a given patient. Their assessment is a complex process that includes such challenges as a dearth of studies that evaluate clinical outcomes and lack of data on use of the test in realistic clinical settings. The methodologic quality of studies of diagnostic tests also lags behind the quality of studies of therapeutic interventions. Statistical methods to combine diagnostic accuracy data are more complex and not as well developed, leading to difficulties in the interpretation of results. The Agency for Healthcare Research and Quality Technology Assessment Program has adopted a 6-level framework for evaluating diagnostic technologies. The model emphasizes the need for systematic reviews of diagnostic test studies to go beyond the assessment of technical feasibility and accuracy to examine the impact of the test on health outcomes. In this paper, we use examples from 3 Evidence-based Practice Center reports to illustrate 3 challenges reviewers may face when reviewing diagnostic test literature: finding relevant studies, assessing methodologic quality of diagnostic accuracy studies, and synthesizing studies that evaluate tests in different patient populations or use different outcomes.

When should functional neuroimaging techniques be used in the diagnosis and management of Alzheimer's dementia? A decision analysis.

BACKGROUND: Functional neuroimaging, including positron emission tomography (PET), has been proposed for use in diagnosing Alzheimer's disease-related dementia (AD). OBJECTIVE: The objective of this study was identify the circumstances under which PET scanning for the diagnosis of AD maximizes health outcomes. METHODS: A Markov-model-based decision analysis was conducted using estimates derived from the literature on AD epidemiology, the accuracy of PET, and donepezil treatment efficacy. The target population for the analysis was assumed to be US men and women who either have mild AD or are asymptomatic but at an elevated risk of developing AD owing to disease in a first-degree relative (parent or sibling). The time horizon was the patient lifetime. We compared treatment 1) based on an American Academy of Neurology (AAN) clinical evaluation either alone; 2) in combination with PET scanning; or 3) empirically based on a family history. Outcomes measures were life expectancy, quality-adjusted life-years (QALYs), and (severe) dementia-free life expectancy (SDFLE). RESULTS: For both patient populations, treating all patients based on an AAN evaluation without further testing using PET resulted in the greatest gains in life expectancy, QALYs, and SDFLEs. PET-based testing was the second preferred strategy compared to no intervention. The rankings of the strategies were sensitive to severity of treatment complications: analyses of hypothetical treatments with the potential for severe complications indicated that testing was preferred if the treatment was effective but had moderate complications. CONCLUSIONS: These results suggest that current treatments, which are relatively benign and may slow progression of disease, should be offered to patients who are identified as having AD based solely on an AAN clinical evaluation. A clinical evaluation that includes functional neuroimaging based testing will be warranted, however, when new treatments that are effective at slowing disease progression but have the potential for moderate to severe complications become available.

Hyperbaric oxygen for treating wounds: a systematic review of the literature.

OBJECTIVE: To determine whether hyperbaric oxygen (HBO) therapy is an effective adjunct treatment for hypoxic wounds. METHODS: We identified studies from technology assessment reports on HBO and a MEDLINE search from mid-1998 to August 2001. We accepted randomized controlled trials (RCTs), cohorts, and case series that reported original data, included at least 5 patients, evaluated the use of HBO for wound care, and reported clinical outcomes. Demographics, wound conditions, HBO regimen, adverse events, and major clinical outcomes were extracted from each study. RESULTS: Fifty-seven studies, 7 RCTs, 16 nonrandomized studies, and 34 case series involving more than 2000 patients are included in this review. None of the studies used wound tissue hypoxia as a patient inclusion criterion. The study results suggest that HBO may be beneficial as an adjunctive therapy for chronic nonhealing diabetic wounds, compromised skin grafts, osteoradionecrosis, soft tissue radionecrosis, and gas gangrene compared with standard wound care alone. Serious adverse events associated with HBO include seizures and pressure-related traumas, such as pneumothorax. A few deaths in the studies were associated with these adverse events. CONCLUSIONS: The overall study quality is poor, with inadequate or no controls in most studies. The studies suggest that HBO may be helpful for some wounds, but there is insufficient evidence to ascertain the appropriate time to initiate therapy and to establish criteria that determine whether patients will benefit. Serious adverse events may occur. High-quality RCTs that evaluate the short- and long-term risks and benefits of HBO are necessary to better inform clinical decisions.

Characteristics of psychiatric patients for whom financial considerations affect optimal treatment provision.

This study assessed characteristics of psychiatric patients for whom financial considerations affected the provision of "optimal" treatment. Psychiatrists reported that for 33.8 percent of 1,228 patients from a national sample, financial considerations such as managed care limitations, the patient's personal finances, and limitations inherent in the public care system adversely affected the provision of optimal treatment. Patients were more likely to have their treatment adversely affected by financial considerations if they were more severely ill, had more than one behavioral health disorder or a psychosocial problem, or were receiving treatment under managed care arrangements. Patients for whom financial considerations affect the provision of optimal treatment represent a population for whom access to treatment may be particularly important.

Variation in routine psychiatric workload: the role of financing source, managed care participation, and mental health workforce competition.

This study was conducted to examine the association between psychiatrists' demographic characteristics, payment source, and managed care participation and psychiatrists' practice workload, and between the supply of other mental health providers in a psychiatrist's county of practice and psychiatrists' practice workload. Data from the 1996 American Psychiatric Association National Survey of Psychiatric Practice were merged with national countywide measures of mental health workforce and environmental data from the 1996 Area Resource File. In comparison to male psychiatrists, female psychiatrists treat fewer patients per week, provide less total hours of weekly patient care, and obtain fewer new monthly referrals. An increase in psychiatrists' managed care participation was associated with only minor increases in the number of patients per week, weekly time spent in clinical care, and number of new monthly referrals. The supply of other mental health providers was not associated with variation in practice workload. Once psychiatrists participate in managed care plans, an increase in their participation rate does not significantly expand clinical practice workload. The supply of other mental health providers was not significantly associated with variation in psychiatrists' workload, which suggests that substitution effects may not be evident with this aspect of psychiatric practice.