In a stern editorial, the editors of the Journal of the American Medical Association write that industry-sponsored research should be analyzed by researchers without ties to the drugmaker that is developing the medicine being studied. And they argue at least one study author must indicate that she or he "had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis."
The missive was prompted by the recent US Senate Finance Committee report, which concluded that GlaxoSmithKline tried to undermine the scientific steering committtee on its own study of its Avandia diabetes pill and failed to acknowledge the drug increased the risk of heart problems. The editorial also pointed to commentary in the same JAMA issue by Steve Nissen, the Cleveland Clinic cardiologist, whose meta-analysis three years ago suggested problems with Avandia. In his JAMA piece, Nissen offers his take on the chain of events surrounding his original publication, including his interactions with Glaxo officials and their handling of their own RECORD trial, which Nissen claims raised questions about its integrity.
For its part, Glaxo has maintained Avandia was studied thoroughly and correctly, and its handling of the RECORD trial was appropriate. But the JAMA editors cite the RECORD trial as a "disturbing example of inappropriate conduct surrounding an industry-sponsored clinical trial of (Avandia) reveals a situation in which concerns about preserving market share apparently trumped concerns about the potential for causing patient harm. Analyzing this situation and others involving misleading reporting and possible misrepresentation of industry-sponsored research has become only too common, and it appears that physicians functioning at several levels failed to put the well-being of patients first."
"It is now time for all editors to require that academic researchers have full access to all trial data and that all industry-sponsored trials include independent statistical analysis and assurance,” wrote JAMA editorsl Catherine DeAngelis and Phil Fontanarosa wrote in the editorial. “This approach would add powerful support to the fundamental principle that physicians must first do no harm.” What do you think? Perhaps there is an argument to be made that this approach may raise unforeseen consequences? Share your thoughts...
Should industry-sponsored trials include independent statistical analysis
- Yes (84%, 82 Votes)
- No (16%, 16 Votes)
Total Voters: 98
14 Comments
Absolutely Yes to access to full trial data.
As an FDA reviewer it's difficult enough dealing with intentionally inappropriately designed studies and intentionally obtuse submissions. However what is unforgiveable is when companies i.e. J&J, Merck, Schering- Plough, Lilly say you have absolutely no right to even see the data they've generated. Of course this is the more detailed data that regarding things you're already seeing hints of issues with safety or manufacturing.
It's also not just the companies. It's FDA management. Simply asking for data results in pressure, requests for data not being forwarded, being pulled off reviews, policy changes, or specific or general directives that reviewers are not to ask for information.
This last one resulted in Janet Woodcock issuing general directives that only "need to know, and not nice to know" information may be requested. Well if I am going to change what I'm going to recommend or do based on the missing information then it's need to know and I never ask unless that's the case.
In other instances it has resulted in review responsibilities, such as assessing the clinical impact of manufacturing changes, being removed from the appropriate review disciplines and instead being given to a group that I won't even describe for obvious reasons. (You can thank Steve Galson for the problems with anticonvulsants.)
Some of these tactics are felonies and sometimes the evidence is there in the FDA reviews that are posted on the internet. Of course our government is so corrupt including OSC that doing anything other than helping the drug companies do whatever they want is futile.
DeAngelis and Fontanarosa write these very strong, holier-than-thou editorials, but their credibility and the quality of their journal has been in a steady decline for years. The scandal last year about the way they wanted to handle a whistleblower on one of their papers is a good example of their loss of credibility.
Instead of spending time pontificating about what other journals should do and asking researchers to jump through more and more hoops, they should pay more attention at their own journal, trying to change the widespread impression that JAMA has become a second- or third-tier journal that is simply not worth reading.
Luca it's called jumping on the bandwagon.
Perhaps they and Insel see the winds changing.
For others you may find the following and the related links at the bottom informative.
http://psychcentral.com/blog/archives/2009/03/19/what-was-jama-and-catherine-deangelis-thinking/
Salmon
You don't have to question the credibility of the JAMA editors to acknowledge we've got a problem with the objectivity of medical research, particularly in 'hot' research areas where money can be made. It's distressing to see how much of the medical literature is really R&D reports from pharmaceutical companies trying to expand indications or manage the information available for their sales reps.
Part of the problem is that, unlike microchips for PCs, there is no fast way for an outsider to purchase a product and test it to see whether the promises made by the label are actually matched by real world performance. Instead someone has to run large, time-consuming trials, and there seem to be only two places that could provide the funding necessary: the pharmaceutical manufacturers themselves, and government research grants. The first group has a clear conflict of interest, and the second doesn't really have sufficient money to hand out [or the political cover to do so].
And that brings me to the 'unintended consequences' part about insisting on independent statistical analyses of trial data: Who would do it? Where would you find truly independent teams to crunch the data? How would they get paid? If fees were levied on pharma to support those independent teams, wouldn't that just reinstate the conflict of interest problems?
It's important that transparency in data analysis be matched by transparency in how the studies were run as a whole, and how the studies got written up for publication as well. The idea that the named authors really did _all_ the work necessary to get a study run, analyzed and published is ludicrous, and we need a way to bring all those hidden forms of assistance into view.
The current Editor-in-Chief of NEJM, Dr. Jeff Drazen had strong ties to industry support before his current position.
http://www.nytimes.com/2000/05/12/us/new-england-journal-of-medicine-names-third-editor-in-a-year.html?pagewanted=1
Of course having the data scrutinized by an independent bio statistician would help matters tremendously.
I think that all investigators working on any trial with industry should scrutinize the raw data and the institutions where they work should provide them with the ability to conduct a full audit. After all the investigators and the institutions credibility are on the line as the key investigators of the study.
It seems rather illogical to have let this process be handled by the drug company.
We should go further. The FDA should make this part of the requirement when the drug is going through the review process. All P.I.'s must sign off that they have had a complete audit done to their satisfaction of the raw data from an independent source, preferably sponsored by their own institution, and this person shall have no contact with the sponsoring company.
But, I am not holding my breath.....
Vet - Re: Drazen and NEJM. I, too, have had concerns as to some of his editorials, in light of his former industry ties. Definitely raises concern as to his independence and lack of bias.
Simply disgusting! Revamp the industry! get rid of the crooks!
I agree with LF -- Who is going to pay for "independent" statisticians and medically-savy people to do all this work? I am in the pharma industry and I frankly do not recall a principal investigator or manuscript author ever even asking for the raw data. The raw data on a relatively small phase I or phase II study is often 6-7 volumes (600 pages of tables and listings per volume). It takes alot of time and effort to make sense of all that. The clinican or academic just wants to see the final report (maybe - not all the time), "tweak" the manuscript and make sure his name and affiliation is correct. I am not criticizing these authors -- they often have meaningful inputs to the study and protocol during its conduct, but to expect them to spend more of their time perusing thousands of pages of raw data, instead of seeing patients or giving lectures does not seem to make sense.
Oh, and another thought -- If a totally independent reviewer from, say Mayo Clinic or the former editorial board of a medical journal, wanted all the raw data and case report forms from a study, would all the investigators on the study have to agree to this? Would they want their clinical judgement to be scrutinized?
Chris, thanks for your post, you have clarified exactly what the problem is.
The institution where the PI is can chose someone they want to partner with whose job it would be to fully and independently scrutinize the data. People who are very well credentialed but are not working would love to have a job like this. The cost is part of doing the study in the first place.
Although it would save many lives, prevent many lawsuits and allow many drug firms to avoid many law suits, it will probably never happen...
This is what the FDA is supposed to do.
Unfortunately as one Medical Division Director yelled in anger, "Our job is to approve drugs".
There are those of us who try to do things honestly and refuse to be corrupted. We don't get anything from companies. I can't even get freebie pens unless I go to a national meeting and get some at a display booth.
It doesn't matter. Fear pervades the place. Look the other way. Cut and Paste.
Janet is the Borg Queen. Resistance is futile.
Of course having the data scrutinized by an independent bio statistician would help matters tremendously.
A fantastic suggestion. Independent verification would help reduce conflicts on interest that inevitably crop up in trials.