{"id":68580,"date":"2016-10-13T20:41:15","date_gmt":"2016-10-14T00:41:15","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=68580"},"modified":"2016-10-13T21:36:06","modified_gmt":"2016-10-14T01:36:06","slug":"congressional-action-time","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2016\/10\/13\/congressional-action-time\/","title":{"rendered":"congressional action time…"},"content":{"rendered":"
This article [Schwartz et al<\/font><\/em>] compares the results found in the ClinicalTrials.gov Results Database with those in Drugs@FDA for 100 drugs up for approval between January 2013 and June 2014. It makes little sense to look at it outside the context of a whole series of articles focusing on ClinicalTrials.gov going back in time. At the end of this post, there are seven abstracts of a representative group of such articles, arranged by year of publication [all available full text on-line]. You might just scan the conclusions before you start…<\/font><\/em><\/sup><\/div>\n
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ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials<\/a><\/div>\n
by Lisa Schwartz, Steven Woloshin, Eugene Zheng, Tony Tse, and Deborah Zarin<\/div>\n
Annals of Internal Medicine<\/font><\/strong>. 2016 165:421-430.<\/div>\n

<\/p>\n

Background<\/font><\/strong><\/em><\/u>: Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear.<\/div>\n
Purpose<\/font><\/strong><\/em><\/u>: To validate results posted on ClinicalTrials.gov against publicly available U.S. Food and Drug Administration [FDA] reviews on Drugs@FDA.<\/div>\n
Data Sources<\/font><\/strong><\/em><\/u>: ClinicalTrials.gov [registry and results database] and Drugs@FDA [medical and statistical reviews].<\/div>\n
Study Selection<\/font><\/strong><\/em><\/u>: 100 parallel-group, randomized trials for new drug approvals [January 2013 to July 2014] with results posted on ClinicalTrials.gov [15 March 2015].<\/div>\n
Data Extraction<\/font><\/strong><\/em><\/u>: 2 assessors extracted, and another verified, the trial design, primary and secondary outcomes, adverse events, and deaths.<\/div>\n
Results<\/font><\/strong><\/em><\/u>: Most trials were phase 3 [90%], double-blind [92%], and placebo-controlled [73%] and involved 32 drugs from 24 companies. Of 137 primary outcomes identified from ClinicalTrials.gov, 134 [98%] had corresponding data at Drugs@FDA, 130 [95%] had concordant definitions, and 107 [78%] had concordant results. Most differences were nominal [that is, relative difference <10%]. Primary outcome results in 14 trials could not be validated. Of 1927 secondary outcomes from ClinicalTrials.gov, Drugs@FDA mentioned 1061 [55%] and included results data for 367 [19%]. Of 96 trials with 1 or more serious adverse events in either source, 14 could be compared and 7 had discordant numbers of persons experiencing the adverse events. Of 62 trials with 1 or more deaths in either source, 25 could be compared and 17 were discordant.<\/div>\n
Limitation<\/font><\/strong><\/em><\/u>: Unknown generalizability to uncontrolled or cross-over trial results.<\/div>\n
Conclusion<\/font><\/strong><\/em><\/u>: Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half the secondary outcomes, as well as serious events and deaths, could not be validated because Drugs@FDA includes only "key outcomes" for regulatory decision making and frequently includes only adverse event results aggregated across multiple trials.<\/div>\n<\/blockquote>\n
In response to the AIDS activists’ insistence on rapid access to drug trials, in 1988 Congress mandated the creation of the AIDS Clinical Trials Information System<\/font> [ACTIS<\/a>]. It was a good idea and over time lead to the creation of ClinicalTrials.gov<\/a>, an online database maintained by the NIH National Library of Medicine<\/font>. By 2007 [Food and Drug Administration Amendments Act of 2007<\/a>], both Registration<\/font> and Results<\/font> reporting on ClinicalTrials.gov<\/font> became mandatory for all FDA regulated drugs.<\/div>\n

But they just didn’t do it. Most trials were registered but often long after they started, and the ClinicalTrials.gov Results Database was the loneliest database on the Internet. There was no enforcement, even from Journal Editors who also claimed to require it. I’ve collected a few of the REFERENCES<\/font><\/strong> below that document the problems from several different angles. But even done right [Registered a priori<\/em> with Results submitted], there are still difficulties. So this system created to promote public transparency just hasn’t worked, and the consequences have become the stuff of legends. Recently, the NIH<\/font>, ClinicalTrials.gov<\/font>, and the FDA<\/font> rolled out a set of reforms designed to correct the things in the ClinicalTrials.gov system. While the effort is appreciated, it was primarily focused on compliance and enforcement – more a commitment to actually do what was supposed to happen in 2007, but uninformed by the multiple real problems in the system today. For example, nobody checks the submitted information, and the deadlines for submission mean that, at best, the information comes after it’s actually needed. On-time is too-late.<\/p>\n

So we have a proposal to Congress known as The Petition<\/a>. It has several parts:<\/div>\n