Corante

About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« "We Had to Clear Out Some Chemists" | Main | Merck Pulls One Out »

January 16, 2014

Should Drug Industry Research All Get Rejected For Publication?

Email This Entry

Posted by Derek

If you work in the drug industry, and for some reason you feel that your blood pressure isn't quite high enough today, a look at this debate at the British Medical Journal should fix that up for you. "Should journals stop publishing research funded by the drug industry?" is the title - there, doesn't that constrict your blood vessels already?

Taking the "Yes, they should" side are Richard Smith (former editor of the journal, now with a British organization called "Patients Know Best", and Peter C. Gøtzsche of the Nordic Cochrane Center. Here's their opening statement, and Gøtzsche's recent opinion piece in the same journal is a good harbinger, as it turns out:

The BMJ and its sibling journals have stopped publishing research funded by the tobacco industry for two main reasons: the research is corrupted and the companies publish their research to advance their commercial aims, oblivious of the harm they do. But these arguments apply even more strongly to research funded by the drug industry, and we suggest there is a better way to communicate the results of trials that would be safer for patients.

Prescribed drugs are the third leading cause of death, partly because of flaws in the evidence published in journals. We have long known that clinical trials funded by the drug industry are much more likely than publicly funded trials to produce results favourable to the company. The reason is obvious. The difference between an honest and a less than honest data analysis can be worth billions of euros, and the fraudulent trials of some cyclo-oxygenase-2 inhibitors for arthritis and selective serotonin reuptake inhibitors for depression are good examples

They're absolutely right about the financial motivations, and a first-rate moral hazard it is, too. But the comparison with the tobacco companies is a real pencil-snapper (as they no doubt intended it to be). They go on about prescription drugs being the "third largest cause of death", about "drug industry crimes", and so on. To be fair, and first let me brush these pencil fragments off my desk, the pharmaceutical companies have laid themselves wide open to these sorts of attacks, painting huge fluorescent bulls-eye targets on themselves again and again. But still.

This piece casually mentions that "olanzapine (Zyprexa), has probably caused 200 000 deaths", footnoting a book by one of the two authors. I seem to have missed that. Many antipsychotic drugs are associated with QT prolongation, which can lead to fatal heart arrythmias, but the worst of them have long been taken out of use. The FDA is investigating two deaths following injection of long-acting olanzapine, not two hundred thousand. Olanzapine has plenty of side effects, though, including weight gain (which can exacerbate Type II diabetes), and it has a warning label in the US about giving it to elderly patients under any conditions. But two hundred thousand deaths? I can't find any support for any such figure; it appears in Gøtzsche's book and apparently nowhere else, so citing it in this article as if it were a well-established fact is a nice move.

Taking the "No" side is Trish Groves of the BMJ itself. She rejects the analogy with the tobacco industry - as she should, because it's offensive and ridiculous. She goes on to detail the problems with industry-reported results and what the journal is doing about them. As opposed to the "Yes" side, it's a pretty reasonable piece. One of the things she mentions is that investigator-led trials have their own sources of bias. Very few people organizing an effort the size of a useful clinical trial will be disinterested in its results, unfortunately.

How much can we trust the evidence base for drugs in current use? It’s hard to tell, given the woeful legacy of widespread non-registration, non-publication, and selective reporting of clinical trials. Much of this reporting bias also applies to investigator led trials, and the many steps now being taken to mandate prospective trial registration, ensure reporting of all results, and access patient level data on interventions’ benefits and harms, as called for by the AllTrials campaign, must apply to them as much as to industry led trials. Moreover, new rules on transparency need to be applied retrospectively: laudable plans to provide access to data on new drugs aren’t enough.

That’s why the BMJ is keen to publish papers from the RIAT (Restoring Invisible and Abandoned Trials) initiative, through which academics who find previously unreported trials can write them up and publish them if the original investigators decline to do so. We also welcome “negative” trials that find no evidence of benefit, as long as their research questions are important and their methods robust, and we’re particularly interested in publishing trials of comparative effectiveness. Both these types of study can be much more useful to clinical practice than the placebo controlled trials that regulators demand. . .

It should be no great task to guess which side of this debate I favor - after all, I'm one of those evil drug company scientists who mow down the customers by the hundreds of thousands. I do wish that Groves' response had strayed a bit from the topic at hand and addressed those accusations of mass murder (that's what they are). I realize that it must be hard to tell a former editor to tone things down and go back for a rewrite. But still.

Comments (46) + TrackBacks (0) | Category: Clinical Trials | The Scientific Literature | Why Everyone Loves Us


COMMENTS

1. Brian on January 16, 2014 9:48 AM writes...

Smith doesn't seem to think much of peer review in general.
http://breast-cancer-research.com/content/12/S4/S13

Permalink to Comment

2. Anonymous on January 16, 2014 9:50 AM writes...

Why don't academics need to declare under the 'Conflict of Interest' statement: "I'm up for tenure/grant renewal" or "I'm applying for professorships and really need this paper?"

Permalink to Comment

3. S Silverstein on January 16, 2014 10:02 AM writes...

The "nays" have a valid point. Abuses of the authoring and publishing processes are significant. However a solution that needs consideration is transparency and reform, not outright bans - and a great deal more skepticism on the part of scientists and researchers.

At the Healthcare Renewal blog, see my WSJ Letter to the Editor of Apr. 8, 2011, referencing Dr. Roy Poses' work.

The link is at http://hcrenewal.blogspot.com/2011/04/medinformaticsmd-and-dr-roy-poses-in.html

The text is as follows, but the source has myriad hyperlinks:

-----------------
April 8, 2011
Wall Street Journal
Letters to the Editor

The Literature Is Hardly Pristine

I find it unfortunate having to inform reader James Reichmann, (Letters, April 1) who prefers his physician to recommend only treatments proven in the "synthesized medical literature," that the very literature on which he wishes his life to depend may be tainted.

As Dr. Roy Poses points out on the Healthcare Renewal Blog, numerous factors common in today's culture can and do corrupt the literature.

The factors include but are not limited to: rampant commercialization of medicine [here, here, here and here], research universities with lax conflict of interest policies [here], faculty as de facto employees of industry through grants [here], academics paid to be "key opinion leaders" to stealth-market drugs and devices [here], control of clinical research given to commercial sponsors [here], conflicts of interest allowing manipulation and suppression of clinical research [here and here], academics taking credit for articles written by commercially paid industry "ghost writers," [here and here], whistleblowing discouraged [here and here], leadership of academic medical centers by business people [here] and medical school leaders becoming stewards (as members of boards of directors) of for-profit health-care corporations [here, here, here and here].

As for me, until the medical literature can be freed of these contaminants, I'd rather trust a well-trained personal physician's good judgment in my own medical care.

Scot Silverstein, M.D.

Drexel University

Philadelphia
-----------------

Full disclosure: I ran MRL's internal scientific libraries 2000-2003 that provided scientists with the published literature. I know we would have been horrified by tainted articles, and I would have banned them from the library if I'd known an article was dishonest.

Permalink to Comment

4. simpl on January 16, 2014 10:07 AM writes...

There is a third camp, who would like publication of all studies, to ensure full visibility. Since motivation would be problematic at all levels, they also seem to be asking for legal enforcement. I wonder how their argument would run with your two protagonists?

Permalink to Comment

5. S Silverstein on January 16, 2014 10:22 AM writes...

@Brian #1 -

I note my own writings since the late 1990s - including submitted papers - on healthcare information technology problems did not get through peer review, because I took a stance at odds with the common belief that electronic medical records and other clinical IT were a miracle cure/panacea/only capable of good.

Only when organizations such as IOM, the Joint Commission, the ECRI Institute (an independent medical technology testing company) and others started to reveal the flaws and risks of the technologies as implemented did these memes become - well, paid more attention to.

Still, when HHS itself puts out methodologically-impaired, faux-systematic-review papers like this in Health Affairs ("The Benefits Of Health Information Technology: A Review Of The Recent Literature Shows Predominantly Positive Results", see http://hcrenewal.blogspot.com/2011/03/benefits-of-health-information.html ) - claiming the technology is wonderful, while ECRI points out in a 2012 9-week voluntary study of just 36 hospitals that there were 171 IT incidents capable of causing harm, and 8 incidents of actual harm possibly contributory to 3 deaths - well, the literature is still not quite sturdy in the Medical Informatics domain.

Permalink to Comment

6. Anonymous on January 16, 2014 10:24 AM writes...

The whole thing is totally stupid. Academics have just as much of a conflict of interest, since they need the publications to achieve promotions, tenure, grants, etc. Academics also have a powerful incentive to shade the truth/lie, and many (many!) do just that. Probably 90% of the published literature is fiction, due in part because of the messed up incentive structure in both industry and academia for generating publications.

Permalink to Comment

7. petros on January 16, 2014 10:39 AM writes...

The deficiencies of academic publishing is highlighted by cases such as Andrew Wakefield's Lancet paper on the MMR vaccine and autism

The scurrilous promotion by journalists and others of this (now withdrawn) article doubtless contributed to death and serious events in many of the infected, unvaccinated, population that it led to.

Permalink to Comment

8. biotech scientist on January 16, 2014 10:43 AM writes...

I think it is important to remember that many drug companies were born out of Universities, whether it was just a few scientists 40 years ago, or a steady stream of scientists from "chosen" institutions over several generations 200 years ago. When drug companies seal off (or in this case, banned?) their people and their work, who outside the company can offer any judgement. Pretty limited view of the trees there. I always knew the Brits were jealous of our pharma.

Permalink to Comment

9. biotech scientist on January 16, 2014 10:44 AM writes...

I think it is important to remember that many drug companies were born out of Universities, whether it was just a few scientists 40 years ago, or a steady stream of scientists from "chosen" institutions over several generations 200 years ago. When drug companies seal off (or in this case, banned?) their people and their work, who outside the company can offer any judgement. Pretty limited view of the trees there. I always knew the Brits were jealous of our pharma.

Permalink to Comment

10. The Iron Chemist on January 16, 2014 10:49 AM writes...

I call shenanigans on their numbers. They claim that "prescribed drugs" is the third leading cause of death, but on the list that I found, it is actually "complications from medical care." Bacterial infections and surgical errors are major contributors to this category. Further, are they including prescription drug-related suicides?

I agree with the listed conflicts of interest for academics. Will I benefit financially from the publication of more manuscripts? You bet! Grants, summer salary, merit-based salary increases, professional awards...

Permalink to Comment

11. Puff the Mutant Dragon on January 16, 2014 11:09 AM writes...

We could just as easily dismiss all academic research on the grounds that academic research is "corrupted" and academics publish research in order to advance their career goals. Dismissing ALL research published by the ENTIRE industry because some of it has issues boils down to about the same thing.

Permalink to Comment

12. MoBio on January 16, 2014 11:11 AM writes...

@anonymous:

" Probably 90% of the published literature is fiction, due in part because of the messed up incentive structure in both industry and academia for generating publications."

Well that is a particularly inflammatory statement...do you have a book chapter you wrote to appropriately buttress your opinion?

Permalink to Comment

13. Hap on January 16, 2014 11:17 AM writes...

I think @12 wins the thread.

Permalink to Comment

14. Anonymous on January 16, 2014 11:28 AM writes...

@9 I can't work out if your last line is serious? You do know that GSK, AstraZeneca, Novartis, Roche, Sanofi etc aren't American companies don't you?

Permalink to Comment

15. Doug Steinman on January 16, 2014 11:41 AM writes...

If prescribed drugs are truly the 3rd leading cause of death (and I doubt that), it is more likely to be due to the fact that most physicians do not take the time to fully review a patient's file before prescribing a new drug and known drug-drug interactions occur with negative consequences. This generally occurs when the patient is seeing more than one physician but that is frequently the case, particularly for elderly patients. Before the physicians start blaming the drug companies for fudging the results of clinical trials and the side effects that were noted, they should consider cleaning up their own act first.

Permalink to Comment

16. Quintus on January 16, 2014 11:43 AM writes...

@14, I can't speak for the others, but who says that Novartis is not an American company? It's management style is distinctly American, the heard of research is American, the CEO is American. The former company chairman and CEO lives in America and probably has dual citizenship.
So I guess you would call it an international organisation (sigh).

Permalink to Comment

17. MoMo on January 16, 2014 11:53 AM writes...

I see socialism creep, pseudo-intellectualism and tyranny are still alive in well in the UK and Norway.

There should be a ban on opinion articles by people trying to justify their existences by writing such ridiculous articles.

And last I heard, Death is the cause of Death.

You buy the drug, you take the ride- Hunter S Thompson

Permalink to Comment

18. Vader on January 16, 2014 11:56 AM writes...

Valid reasons for not publishing research include:

It duplicates well-established results and thus does not advance the science.

Peer reviewers conclude it was badly carried out and thus unreliable.

It comes from a source previously shown to have committed scientific fraud.

All else is ad hominem. If the researcher is biased, that should be evident in how the research was conducted, analyzed, or interpreted. Concluding it must be biased because of the perverse incentives the researcher had is a logical leap we should not, as scientists, allow ourselves to make. We need to actually find evidence of bias in the research itself, not the researcher.

Permalink to Comment

19. RAM on January 16, 2014 11:57 AM writes...

@16, Novartis does
http://www.us.novartis.com/about-novartis/index.shtml

Permalink to Comment

20. bacillus on January 16, 2014 12:22 PM writes...

@15. I agree with your assessment. My mother had multiple myeloma accompanied with kidney failure. She was taking many drugs for each indication, and several of them overlapped since her oncolgist and nephrologist were at different hospitals and didn't communicate with one another. Consequently, she was double dosing on a number of her meds. Moreover, I have no doubt that the combinations of drugs she was taking had never undergone any kind of tox study. I believe this is where most of the death by medicine occurs.

Permalink to Comment

21. bacillus on January 16, 2014 12:22 PM writes...

@15. I agree with your assessment. My mother had multiple myeloma accompanied with kidney failure. She was taking many drugs for each indication, and several of them overlapped since her oncolgist and nephrologist were at different hospitals and didn't communicate with one another. Consequently, she was double dosing on a number of her meds. Moreover, I have no doubt that the combinations of drugs she was taking had never undergone any kind of tox study. I believe this is where most of the death by medicine occurs.

Permalink to Comment

22. Lyle Langley on January 16, 2014 12:25 PM writes...

@6, anonymous: " Probably 90% of the published literature is fiction, due in part because of the messed up incentive structure in both industry and academia for generating publications."

@12, MoBio: "Well that is a particularly inflammatory statement...do you have a book chapter you wrote to appropriately buttress your opinion?"

But based on his statement, 90% of his own book chapter would be fiction, so where does that leave us?

Permalink to Comment

23. Dave M. on January 16, 2014 12:33 PM writes...

For many of you not in the world of clinical Pharma, the FDA and EMEA get FULL AND UNRESTRICTED access to the locked database for every Phase 2 and 3 (pivotal) or label enhancing trial. The database is locked and signed with an encrypted key that will not be matched if the database is altered.

The FDA then writes their own SAS programs and statistical analysis plan to analyze the database.

Have you ever been to an FDA Advisory Committee where the FDA completely blindsides the Pharma company by presenting some of their own analyses that they did? Pharma-biased publishing of trials where the FDA has access to their database most often would be caught.

CROs now monitor in REAL TIME entries into the database by investigators, and analyses are run to detect signals of an Investigator entering false information, wrong information, or just randomly entering to data to catch up.

I'm not arguing in favor of Pharma, because there are still issues.

However this is like arguing that cars are just way too dangerous based on highway safety data BEFORE crumple zones, airbags, and anti-lock breaks were widely implemented.

The main issue is that Regulatory Authorities have severely narrowed what "substantial evidence of efficacy" means to them, and honed in on "pseudospecificity" issues.

Real world pragmatic designs are almost never allowed for pivotal studies, which would really filter out the bad drugs a heck of a lot more often.

Simply offering Pharma some patent extensions now on a leading drug of their choice in exchange for giving database access to Regulator for ALL trials conducted could make the issues of publication much more transparent.

Allowing pragmatic designs for pivotal trials could solve the "hey this drug works great in this narrow patient subset bu sucks in the real world".

Permalink to Comment

24. Tuck on January 16, 2014 12:47 PM writes...

"...I'm one of those evil drug company scientists who mow down the customers by the hundreds of thousands."

Keep up the good work. ;)

In the after-life, all research will be conducted in a manner absent fault. In the real world, debates like this are a good sign, even if they cause pencils to snap.

Permalink to Comment

25. Anonymous on January 16, 2014 12:48 PM writes...

If only there was a magical place, where information could be stored, accessible by anyone, cheaply.

Permalink to Comment

26. Da Vinci on January 16, 2014 1:18 PM writes...

Yes of course they should. No brainer.

You know, at one point this used to be an interesting blog about chemistry and pharmacology. Now it's just turning into another American libertarian nonsense political blog. Such a shame.

Permalink to Comment

27. Not a doctor on January 16, 2014 2:02 PM writes...

I can see Rx drugs being one of the top causes of deaths if you include opoid/polydrug abuse. Lots of folks are taking stupid doses of Oxycodone.

Permalink to Comment

28. emjeff on January 16, 2014 3:37 PM writes...

Glad that they shared their feelings - I won't be sending anything else to them, then.

Permalink to Comment

29. Anon on January 16, 2014 4:21 PM writes...

It seems commenters are taking the statement "Prescribed drugs are the third leading cause of death" to invalidate the points about the effects of conflict of interest affecting the literature.

Let's say - I'll make it up - drugs are the 15th leading cause of death. There, settled.

Now - what about the points about the literature?

Permalink to Comment

30. Pennpenn on January 16, 2014 7:54 PM writes...

How'd you figure? Or is any voice that doesn't agree with what you're saying count as "libertarian nonsense political" speak?

Permalink to Comment

31. Anonymous on January 17, 2014 7:16 AM writes...

The tobacco industry does far more for society than pharma, by killing people before they draw on their state pensions and other health and welfare benefits. Compare that to keeping useless old people alive at great expense for years, just so they can go on being a huge drain on society, and vote to carry on with this crazy ponzi scheme.

Permalink to Comment

32. MTK on January 17, 2014 8:15 AM writes...

simpl, comment 4, is on the right track here IMO

The fact that industry funded published studies are skewed toward results favoring the company does not necessarily mean the studies are false or rigged. It's just that many negative studies never see the light of day.

Permalink to Comment

33. petros on January 17, 2014 8:31 AM writes...

Re #31,
The tobacco industry also accounts for nearly all patients with COPD, the majority of lung cancer cases and a major proportion of serious CV disease

Permalink to Comment

34. jbosch on January 17, 2014 8:43 AM writes...

@25

In Europe you can access clinical trial data
https://eudract.ema.europa.eu

Permalink to Comment

35. Anonymous on January 17, 2014 8:43 AM writes...

@33: Yep, and I'm one of them, so thank the tobacco industry for ensuring that I won't be around sucking our/your society dry when I (don't) get old.

Permalink to Comment

36. simpl @MTK (#32) on January 17, 2014 9:16 AM writes...

Sorry, if I wasn't clear. Bias towards interesting results is true, and part of science, and wasn't really my point.
I'm more concerned by the idea of forcing the publishing of non-interesting results. It makes for a bad newspaper, and would turn many a research journal into a garbage collector. In #23 Dave M describes nicely how far this goes today.

Permalink to Comment

37. RM on January 17, 2014 10:34 AM writes...

Vader@18 - Exactly

Biases in publishing are usually displayed through selective reporting. While "publish nothing" is one way to solve a positive/negative result bias, perhaps the better way is to publish *more*. Instead of blacklisting pharma, she should be twisting their arm to publish all the skeletons in their closets.

Permalink to Comment

38. MTK on January 17, 2014 10:41 AM writes...

@36 and 37,

Yeah, that's what I meant. Publish more rather than less.

Although I do understand your concern simpl that it doesn't make for as interesting reading most times.

Permalink to Comment

39. qetzal on January 17, 2014 12:47 PM writes...

Yes, but the concern is that Pharma routinely withholds data that makes their drugs look bad. So, in this case, making Pharma publish more is guaranteed to be interesting. If it contradicts the 'good' data, that's interesting. If it actually confirms the good data, that's still interesting because it refutes the original charge about Pharma withholding bad data.

Permalink to Comment

40. paper_CRF on January 17, 2014 4:40 PM writes...

Like paper CRFs, traditional journals are an anachronism. Let BMJ stop publishing drug-funded research. It's a rag, and it doesn't matter. Soon, regulators will have the authority to post online all industry-sponsored studies of approved drug products for everyone to view and (and copy and comment on). Eventually, summary study results will be supplemented with, or perhaps supplanted by, by data standards-compliant full datasets, and scholars will be free to re-analyze and meta-analyze the results to their hearts' content.

Permalink to Comment

41. Steven McKinney on January 18, 2014 12:37 AM writes...


"I can't find any support for any such figure; it appears in Gøtzsche's book and apparently nowhere else, so citing it in this article as if it were a well-established fact is a nice move."

I found support for such a figure with a few minutes of diligent searching. A print of Gotzsche's chapter 18 is available at

http://www.radcliffehealth.com/sites/radcliffehealth.com/files/samplechapter/gotzsche_chpt18.pdf

Gotzsche references

Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005; 294: 1934-43. (Reference 79 discussed below)

Dyer O. Lilly investigated in US over the marketing of olanzapine. BMJ. 2007; 334: 171. (Reference 78 discussed below)

The Schneider et al. meta-analysis reports

"Expressing the absolute risk difference as an inverse yields a number needed to harm of 100 with a very broad 95% CI from 53 to 1000, implying that there may be 1 death due to atypical drug use for every 100 patients treated over 10 to 12 weeks. Considering that many of these trials demonstrated that these medications are only modestly effective with numbers needing to treat ranging from 4 to 12 in specific metaanalyses, the likelihood for helping vs harming may be rather modest as well, such that for every 9 to 25 persons helped in these trials there possibly will be 1 death."

A meta-analysis of many trials is in this statistician's opinion pretty much a well established fact.

Gotzsche reasons as follows:

"Let's estimate how many people Lilly has killed with Zyprexa. In 2007, it was reported that more than 20 million people had taken Zyprexa. (ref 78) A meta-analysis of the randomised trials of olanzapine and similar drugs given to patients with Alzheimer's disease or dementia showed that 3.5% died on drug and 2.3% on placebo (P = 0.02). (ref 79, the Schneider et al. paper cited above) Thus, for every 100 patients treated, there was one additional death on the drug. Elderly patients are often treated with several drugs and are more vulnerable to their harms, which means that the death rate is likely higher than in younger patients. However, the reviewed trials generally ran for only 10-12 weeks, and most patients in real life are treated for years."

Note that Gotzsche did not quote the higher harm rate alluded to in the meta-analysis, "for every 9 to 25 persons helped in these trials there possibly will be 1 death". So Gotzsche is not just grabbing at the highest harm figure available.

Now we are all going to die, but there is plenty of evidence that people are dying sooner than they needed to, because of the insatiable need for drug companies to increase their sales figures. Human health should not be held hostage to the profit mandate codified in U.S. law. "Increasing shareholder value" at the expense of millions of healthcare patients quality (and quantity) of life is deplorable.

Permalink to Comment

42. kemist on January 18, 2014 10:13 AM writes...

Don't you think people "in the know" already ignore such publications.

People underestimate the value of phoney science, investors and "scientists" make money from it every day.

People who lived in poverty for so many years to get their education are all too willing to jump on board.

History will show that these times will be considered a setback in the progress of healthcare.

Permalink to Comment

43. Lloyd T J Evans on January 18, 2014 3:45 PM writes...

Refusing to publish papers authored by (or funded by) those in the Tobacco industry is completely different from refusing to publish papers funded or authored by Pharmaceutical industries. For the simple reason that Tobacco products are neither designed or intended to improve health in any way. Neither are Tobacco products designed or intended to treat or cure any disease. So the primary justification for excluding Tobacco related "science" from medical journals is lack of relevance. The fact that such "science" is likely to be biased at best and outright fraudulent at worst is a secondary justification.

Having said that, there clearly are problems of bias with respect to publishing of science which has been funded by Pharmaceutical industry. The solution however is not to simply refuse to publish science which might be biased.

Any competent scientist doing research will never (or should never) rely on just one source of information. Good scientists not only use multiple sources, but also analyse potential bias in those sources to determine which are the most trustworthy. Therefore what we have to do is make potential (or actual) bias obvious, or at least much easier to spot.

To make this possible, two important changes have to be made:

1. Whenever ANY clinical trial is done, the results MUST be published, even if the results are inconclusive.

2. All research papers must explicitly state who funded the research. No matter whether it was government research council, a charitable institute, or private business. If there are multiple sources of funding, then all must be listed - the biggest source first.

This will accomplish two objectives:

1. Nobody will be able to hide (by failing to publish) results which do not agree with whatever conclusion they would like to draw. This will force any and all such conclusions to be more honest.

2. Sources of potential bias will be immediately evident for all published research. Anyone reviewing such research will therefore be able to much more accurately determine how trustworthy it is. This will (sooner or later) force the authors of any research to become more honest.

Finally, I would agree that bias is not a problem restricted only to research funded by private business. Academic researchers are not completely immune. Academics can be (and often are) under pressure to publish research in order to justify grant applications, or to advance their careers. But there is an important difference:

The pressure on academic researchers forces them to either publish more papers, or publish higher quality papers in more prestigious journals.
Unless their research is being funded (either partially or wholly) by private businesses, academics are rarely under pressure to distort the conclusions drawn from within the actual research. Motivations to obtain funding to do research might be dishonest, but there is no inherent source of bias influencing the research itself.

Whereas whenever private business is funding research, the chances are that some conclusions will be looked upon more favourably than others. Therefore any such research has an inherent bias from the very beginning - researchers are under pressure to produce conclusions the business wants, and to hide results which don't support said conclusions.
This is why all studies must be published, and why explicitly identifying sources of funding is of utmost importance.

Permalink to Comment

44. sciencemonkey on January 20, 2014 1:44 PM writes...

@43 Lloyd

Good post, but I must disagree with one point. Like others have written in this thread, academics are under pressure to distort conclusions, because journals are interested in publishing positive and interesting results.

Permalink to Comment

45. DH on January 21, 2014 2:36 PM writes...

"Unless their research is being funded (either partially or wholly) by private businesses, academics are rarely under pressure to distort the conclusions drawn from within the actual research."

I completely disagree. Academics are under enormous pressure to publish *novel* work. If you do an experiment and its results simply confirm what everyone already knew, you are much less likely to succeed in publishing it. Thus, you have incentive to analyze or spin the results to look novel even if they are not. With all the watchdogs breathing down industry's neck, and very few doing the same for academia, I would not be surprised if the problem of bias in published research is greater for academia than for industry.

Permalink to Comment

46. Josh on January 22, 2014 10:23 PM writes...

Why don't we ask the millions of people who are *not* dead because of antiretroviral drugs how they feel about this?

Permalink to Comment

POST A COMMENT




Remember Me?



EMAIL THIS ENTRY TO A FRIEND

Email this entry to:

Your email address:

Message (optional):




RELATED ENTRIES
Scripps Update
What If Drug Patents Were Written Like Software Patents?
Stem Cells: The Center of "Right to Try"
Speaking of Polyphenols. . .
Dark Biology And Small Molecules
How Polyphenols Work, Perhaps?
More On Automated Medicinal Chemistry
Scripps Merging With USC?