Posted on Sunday 8 September 2013

by Elizabeth Wager and Peter Williams
British Medical Journal. 2013 347:f5248 published on-line September 6, 2013
[full text on-line]

Objectives To determine the proportion of medical journals requiring trial registration and to understand their reasons for adopting [or not adopting] such policies and other measures designed to reduce publication bias.
Design Quantitative study of journals’ instructions to authors [in June 2012] and qualitative study of editors’ and publishers’ views on trial registration and publication bias [carried out in Autumn 2012].
Setting Random selection of 200 medical journals publishing clinical trials identified from the Cochrane CENTRAL database.
Participants Editors [n=13] and publishers [n=3] of journals with different policies on trial registration [and with recently changed policies] identified from the survey of their instructions to authors.
Results Only 55/200 journals [28%] required trial registration according to their instructions and a further three [2%] encouraged it. The editors and publishers interviewed explained their journals’ reluctance to require registration in terms of not wanting to lose out to rival journals, not wanting to reject otherwise sound articles or submissions from developing countries, and perceptions that such policies were not relevant to all journals. Some interviewees considered that registration was unnecessary for small or exploratory studies.
Conclusions Although many major medical journals state that they will only publish clinical trials that have been prospectively registered, and such policies have been associated with a dramatic increase in the number of trials being registered, most smaller journals have not adopted such policies. Editors and publishers may be reluctant to require registration because they do not understand its benefits or because they fear that adopting such a policy would put their journal at a disadvantage to competitors.
This is a long article, reasonably lamenting the fact that most Clinical Trials aren’t registered, that many journals don’t require registration, and addressing the non-publication of negative trials. I was scanning along, and hit this paragraph early on:
Quantitative study
We obtained a listing of all journals included in the Cochrane Central Register of Controlled Trials [CENTRAL] database from 2009 to 2011. This database includes randomised trials from a wide range of sources [including literature searches from bibliographic databases, hand searches undertaken as part of systematic reviews, and retrieval of articles from the reference lists of other articles obtained by both these methods]. The list was downloaded into an Excel spreadsheet, deduplicated, and sorted alphabetically by journal title, producing a total of 3512 journals. A series of 200 random numbers from 1 to 3512 was generated using www.random.org. We extracted journal titles corresponding to these numbers in the Excel listing and entered these into a search engine via a web browser [Google accessed via Mozilla Firefox] to locate the journal website. If no website could be found, or the journal did not provide instructions in English, we selected the next journal on the Excel spreadsheet. In this way we created a sample of 200 journals thought to publish clinical trials.
I tried to keep scanning the article, but I was stuck on that number – 3512 Journals publishing Clinical Trials! So I stopped scanning and revisited the ACRO [Association of Clinical Research Organizations] to look at their numbers. I had an ADHD moment when I ran across a press release about Ben Goldacre’s Bad Pharma [it could've been titled Bad Ben]. But after that diversion, I found this:

CRO industry revenue was estimated at $33.6 billion for 2012 and is expected to reach $37.4 billion in 2013, according to Industry Standard Research. Please note that estimates of industry size can vary as the definition of "CRO" and the scope of services included in market size may differ from source to source. According to the independent Tufts Center for the Study of Drug Development, clinical trials conducted by CROs are completed an average of 30 percent more quickly than those conducted in-house. This results in an average time savings of some four to five months, translating to $120 million to $150 million in increased revenue potential.

ACRO member companies employ approximately 95,000 people worldwide. Each year our members conduct more than 11,000 clinical trials in 115 countries involving nearly two million research partitipants. ACRO memebr companies have contributed to the development of all of the top 50 selling bipharmaceutical products globally and the participate in the development of the vast majority of new treatments and therapies approved globally each year. The top five therapeutic areas for CROs are: oncology, CNS, infectious disease, metabolic disorders and cardivascular disease. Vaccine development is another growing area of research for CROs.  

ACRO member companies manage nearly one million square feet of laboratory space, process more than 16 million samples each year and deliver more than 60 million individual test results.  Approximately two-thirds of CRO business is from the pharmaceutical industry, 27 percent from biotech and the remainder funded by the medical device, foundation and government sectors. Approximately 46 percent of clinical trials are conducted in the United States, 30 percent in Europe and the remainder in Asia, Latin America, Africa and the Middle East. An analysis of data quality that appeared in the Drug Information Journal found that there were no statistically significant differences in data quality between or among regions or countries.
$33.6 Billion/Year? 11,000 Clinical Trials/Year? in 115 Countries? with 2 million Participants in a Year? published in 3512 Journals? Note that 2/3+27%=93% of their business is from PHARMA+Biotech. 93% of 11,000 is at least 10,230 commercial Clinical Trials/Year! I find all of these numbers staggering. Last night, I was speechless and went to bed. I didn’t pick it back up until this evening, and I still feel a kind of tongue-tied. I had previously read the paper referred to in the blue highlight as well as their white paper on globalization and found them as silly as the review about Ben’s book [which was pretty damned silly].

I went back and finished the paper I started with. It was pretty interesting on the whys and wherefores that Clinical Trials aren’t registered and Journals aren’t particularly helpful, but I couldn’t help thinking that it’s because it’s all voluntary – as they say in the title "Hardly worth the effort." It was written by members of the OPEN Project [Overcome failure to Publish nEgative fiNdings] Consortium. With that many Clinical Trials, they’ve got their work cut out for them.

I can find no way to see these numbers as close to necessary for progress in  medical science. This is an industry as out of control as its evil twin, PHARMA. Watching this duo have such a negative impact on psychiatry has been painful enough. To see it operating Medicine wide is even worse. For data transparency to work with 11,000 Clinical Trials/Year, we may need to reinstitute the draft for an enforcement army. Perhaps a better approach would be to put some reasonable restrictions on the inappropriate overuse of Clinical Trials…
    September 8, 2013 | 9:17 PM

    So it has come to this: No patient or practitioner can (or should) trust clinical trial study results. I think we have hit rock bottom. This is seriously depressing.

    September 8, 2013 | 11:03 PM

    One journal to rule them all, one journal to bind them.

    September 9, 2013 | 12:16 AM

    I think most of the problem stems from not having legal requirements for the quailifications of peer reviewers.

    As it currently stands, it’s up to the Journal to determine what qualifications it’s peer reviewers should have. I guess that works exceedingly poor in practice.

    I think that’s something that could realistically be fixed. I just don’t know how it’ll ever happen?

    September 9, 2013 | 4:36 AM

    “As of 2007, not a single U.S. government researcher had been prosecuted for human experimentation, and many of the victims of U.S. government experiments have not received compensation, or in many cases, acknowledgment of what was done to them.”
    ^ Henry N. Pontell, Gilbert Geis, ed. (2007). International handbook of white-collar and corporate crime. Springer. p. 62. ISBN 978-0-387-34110-1.

    September 9, 2013 | 6:18 AM

    Of course our lamblike, moralistic contractors would never be tempted to spin data in clinical trials would they?

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