More evidence that regulations are what Prof. Ben Goldacre calls “pseudo fixes”.  Regulations without penalties for violations and/or the failure to enforce regulations are the norm.  More window dressing from industry and government regulators.  Only 29% of registered trials complied with the requirement of publication within 2 years.  Only 13% of trials bothered to register. The fault is not with the academic medical centers, but with industry that requires the signing of a contract which gives the sponsor control over all aspects of the data.  This permits pharma to change primary endpoints, to manipulate the categories, to dived categories such as for side effects, to run a wash-out period (to give the volunteers the drug, check the results, drop out volunteers, and then start the trial) and to fraudulently tally results.  These contracts gives pharma the control over the design of the trial.  By contracting out the trials it gives an appearance of non-involvement of industry.  For those who want to know more, there are two excellent books: Bad Pharma, by Prof. Ben Goldacre, and The Truth about Drug Companies, by Professor Marcia Angell.  The article below fails to address the issue of industry’s approach to clinical trials, namely as tools for marketing their drugs.  Angell and Goldacre highlight this reality.     

As Ben Goldacre states:  “The devil is in the details.”   Thus for example what seems like a high (effective) dose of CoQ10, 2400 mgs, is in fact a low dose—see.  The enzyme is given as a chewable wafer taken orally in a study on its effect upon Huntington’s disease.  However, in that form only 10% is absorbed, while suspended in oil which has over twice the absorption rate. 

http://www.bmj.com/content/352/bmj.i637   2/22/16

Researchers find noticeable variation and poor performance in the dissemination of clinical trial results

Dissemination of clinical trial results by leading academic medical centres in the United States remains poor, despite ethical obligations - and sometimes statutory requirements - to publish findings and report results in a timely manner, concludes a study in The BMJ this week.  Researchers found that only 29% of completed clinical trials led by investigators at major US academic centers were published within two years of completion and only 13% reported results on the largest clinical trial registry, ClinicalTrials.gov.

They say action is needed to rectify this lack of timely reporting and publication, as they impair the research enterprise and threaten to undermine evidence based clinical decision making.� Randomized clinical trials are the ideal means for evaluating the efficacy and safety of medical drugs and devices. Timely dissemination of trial results is required to honor the commitment of study participants, advance the scientific process, and improve clinical care, but little is known about the performance of academic medical centers in this endeavor.

US law also requires that certain trials be registered and their results posted.  Yet previous studies have shown that between 25% and 50% of clinical trials remain unpublished, sometimes years after completion, and that the results of many trials are not reported promptly on trial registries.  So, a team led by Professor Harlan Krumholz at Yale School of Medicine, examined rates of publication and reporting of results within two years for 4,347 registered trials completed between October 2007 and September 2010 across 51 leading US academic institutions. Results show that only 29% (1,245/4,347) of completed clinical trials led by investigators at major US academic centers were published within two years of study completion and only 13% (547/4,347) reported results on ClinicalTrials.gov.

The study also revealed marked variation in rates of dissemination of clinical trial results across academic institutions, with more than a twofold variation in the average time from study completion to dissemination of results and more than a threefold variation in the rate of dissemination across institutions.  However, no academic center published more than 40% of completed clinical trials within two years of completion or reported results for more than 41% of its trials.  We found noticeable variation and poor performance across leading academic medical centers in the dissemination of clinical trial results, write the authors. And they point out that there is no effective enforcement mechanism and no repercussions to academic institutions or individual investigators for failing to report results.

The lack of timely reporting and publication fundamentally impairs the research enterprise, violates the commitment made by investigators to patients and funders, squanders precious time and resources, and threatens to compromise evidence based clinical decision making, they conclude.

Link to paper

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JK has put in just a few pieces from the complete article. 

http://www.bmj.com/content/352/bmj.i637   BMJ 2/17/16  Cite this as: BMJ 2016;352:i637

Abstract

Objective To determine rates of publication and reporting of results within two years for all completed clinical trials registered in ClinicalTrials.gov across leading academic medical centers in the United States.

Design Cross sectional analysis.

Setting Academic medical centers in the United States.

Participants Academic medical centers with 40 or more completed interventional trials registered on ClinicalTrials.gov.

Methods Using the Aggregate Analysis of ClinicalTrials.gov database and manual review, we identified all interventional clinical trials registered on ClinicalTrials.gov with a primary completion date between October 2007 and September 2010 and with a lead investigator affiliated with an academic medical center.

Main outcome measures The proportion of trials that disseminated results, defined as publication or reporting of results on ClinicalTrials.gov, overall and within 24 months of study completion.

Results We identified 4347 interventional clinical trials across 51 academic medical centers. Among the trials, 1005 (23%) enrolled more than 100 patients, 1216 (28%) were double blind, and 2169 (50%) were phase II through IV. Overall, academic medical centers disseminated results for 2892 (66%) trials, with 1560 (35.9%) achieving this within 24 months of study completion. The proportion of clinical trials with results disseminated within 24 months of study completion ranged from 16.2% (6/37) to 55.3% (57/103) across academic medical centers. The proportion of clinical trials published within 24 months of study completion ranged from 10.8% (4/37) to 40.3% (31/77) across academic medical centers, whereas results reporting on ClinicalTrials.gov ranged from 1.6% (2/122) to 40.7% (72/177).

Conclusions Despite the ethical mandate and expressed values and mission of academic institutions, there is poor performance and noticeable variation in the dissemination of clinical trial results across leading academic medical centers.

Publication rates

Of the 4347 trials in our analysis, 2458 (56.5%) had been published as of July 2014. The time (months) from primary completion date to publication varied significantly, with 1245 (28.6%) having been published within two years and 952 (21.9%) more than 24 months after the primary completion date. Overall, 261 (6.0%) trials had a publication date that preceded the primary completion date; we excluded these from analyses of timing but counted them as having been published. The median publication time for these 2197 trials was 22.3 (interquartile range 14.0-33.0) months (see supplementary figure 1).

Rates of publication of results from completed clinical trials as well as median time from study completion to publication varied considerably across academic institutions (table 2⇑). The proportion of clinical trials published within 24 months of study completion ranged from 10.8% (4/37) to 40.3% (31/77) across academic institutions. The overall rate of publication of clinical trial results ranged from 35.0% (13/37) to 67.2% (43/64) and the median time from study completion to initial publication of findings ranged from 14.5 to 30.8 months.

Results reporting

Of the 4347 completed clinical trials, 1166 (26.8%) reported results on ClinicalTrials.gov as of July 2014. The time (months) from primary completion date to results reporting varied significantly, with 547 (12.6%) trials reporting results within 24 months and 617 (14.2%) more than two years after the primary completion date. Two trials had a results reporting date that preceded the primary completion date; we excluded these from analyses of timing but counted them as reporting results. The median time from study completion to results reporting for these 1164 trials was 26.1 (interquartile range 16.4-36.6) months (see supplementary figure 2⇑).

Rates of results reporting on ClinicalTrials.gov for completed clinical trials as well as the median time from study completion to results reporting varied considerably across academic institutions (table 2⇑). The overall rate of results reporting of clinical trials ranged from 4.1% (5/122) to 55.4% (98/177). The median time from study completion to results reporting varied from 13.9 to 46.7 months, whereas the rate of results reporting within two years of study completion ranged from 1.6% (2/122) to 40.7% (72/177) across academic institutions.