These past few weeks a fascinating story came out about a researcher whose work was funded in part by a pharmaceutical company who is then later sued and threatened by the same company for publishing the research findings. Pretty intense. As you might guess, the findings were not favorable to the company, and they are claiming that the publication causes them financial harm, and are demanding a retraction or modification of the paper to reduce the economic harm to the company.
I haven’t given you any of the details yet, so let’s look at this cautiously. What questions be asked to determine who is the actual wronged party here?
* How authoritative or reputable is the research?
* Where was it published?
* Where there other funding sources?
* Is there actual economic harm to the company?
* Since this is a pharma company, it is about a drug, so it needs to be asked whether the drug causes actual harm to people?
* If yes, how serious is the harm to patients?
Weighing costs, benefits, and credibility. Now the answers, from my own personal point of view, with only the info ready to hand. I’m not doing any serious research into this, just looking at what is easily and readily available. If you have better information, please add that in the comments.
How authoritative or reputable is the research?
The article has 32 authors representing two major ongoing clinical trial research projects, specifically 6S Trial Group and the Scandinavian Critical Care Trials Group. It was a multicenter, parallel-group, blinded trial. The 6S Trial collected data from December 2009 to March 2012, with a sample size of 804, with this as the first report based on the final and complete data collection. I don’t know enough to comment on the methodology, but the peer review process of the Institutional Reviews at the various organizations involved with the trial should presumably have already done that.
Where was it published?
Was this in some rinkydink fly-by-night minor journal with only superficial peer review? Not at all. This contested article was in the New England Journal of Medicine, one of the very top most influential and highly regarded journals in all of healthcare.
Were there other funding sources?
Indeed there were. The article states the work was “Supported by grants from the Danish Research Council (271-08-0691 and 09-066938), the Rigshospitalet Research Council, and the Scandinavian Society of Anesthesiology and Intensive Care Medicine (funded by the ACTA Foundation).” Quite important and credible organizations that would have also reviewed the research methodologies before funding.
Is there actual economic harm to the company?
I don’t have a clue how many hospitals actually use the medication that was tested versus the comparison medication (yes, details to be revealed shortly), however when there is a recommendation that a medical cease being used for a given purpose, there will of course be economic impacts. How much impact would depend on whether the drug is safe for other purposes, and the size of the potential patient base. In the email list where I first heard about this, questions were asked about if the drug company could improve the medication, or test it for alternative uses.
In my mind, the larger question is whether the economic harm to the drug company could possible be larger than the harm they are doing to their overall reputation through this lawsuit.
Since this is a pharma company, it is about a drug, so it needs to be asked whether the drug causes actual harm to people?
The test was comparing two medications used with patients who have severe sepsis. This is a very serious condition that can be fatal, and in survivors can cause permanent organ damage. Some survive without apparent lasting harm, but data shows that even survivors in good health are at increased risk of death even many years later.
So the condition being treated is extremely serious. If a person is at risk of possibly dying, then every potential impact on survival, duration of life, and quality of life become huge. The findings of the study showed that the drug 1, compared to drug 2, was likely to cause additional harm to the patient and did not significantly extend either the duration or quality of life. In popular language, three strikes and you’re OUT! I would not want this med used on me for this purpose.
If yes, how serious is the harm to patients?
Pretty darn serious. People died more often, died faster, and were in more pain while dying. Nasty stuff.
The doctors on the email list had some pretty strong language to use while discussing this and the general ethics associated with the company suing the researcher. According to what I heard, it isn’t just this one study that shows concerns with using this medication. On the other hand, there is other research showing that this med is safe for infants and children, so it could be simply that it is a poor choice for this specific condition (sepsis).
It is probably a good idea to do more research about this drug for various purposes in many populations. Or perhaps this is simply a case of the science improving and moving to better treatments as they are discovered, leaving behind what was, at one time, the treatment of choice.
Pulling back the curtain now. If you haven’t already guessed, the actual article that is being contested is this one by Anders Perner.
Perner A, et al. Hydroxyethyl Starch 130/0.42 versus Ringer’s Acetate in Severe Sepsis. N Engl J Med 2012; 367:124-134. July 12, 2012 http://www.nejm.org/doi/full/10.1056/NEJMoa1204242#t=articleBackground
So who is doing what to poor Dr. Perner?
July 24, 2012
Science Nordic: Pharma giant threatens Danish scientist: http://sciencenordic.com/pharma-giant-threatens-danish-scientist
Based on that information various observers were upset and wanted the opportunity to communicate to Fresenius Kabi about their concerns. A large part of the concern was the effort to silence scientists about life-saving matters, and to change the scientific record. A petition was created.
Change.org: Fix Drug, Don’t Sue: http://www.change.org/petitions/fix-drug-don-t-sue
I’ve learned to not trust the information in Change.org petitions, so did some research on my own, and then went ahead and signed it. Here is what I said.
The goal of pharmaceutical research is to discover ways to improve the health and lives of living beings (people, animals, and plants). That this is the goal of Fresenius Kabi is supported by their mission statement, which includes the bold text, “Caring for life.” The nature of research is such that there is often insufficient evidence to support a claim, making it difficult to decide just how best to support “caring for life”. The correct strategy for disagreements about what is best is, first, to do more research and make sure there IS enough evidence to support a particular point of view; and second, in the meantime, to make the best decision possible for a particular patient based on the clinician’s knowledge of that patient, the patient and caregiver’s desires, and the evidence available at that time. To threaten researchers with punitive lawsuits is a strategy that is most likely to instead cause harm to both patients and the future of scientific enquiry on that question (possible scientific enquiry overall!). It is absolutely critical that this lawsuit be withdrawn as damaging to the nature of scientific enquiry as well as irresponsible, unethical, and contrary to the mission of Fresenius Kabi.
That was a few days ago. Now, continuing to follow the case, I learn more. There are questions about which formulation of the medicine was used, are the numbers significant, what is the actual risk. And when you did further, was there even really a lawsuit or threat of one?
August 2, 2012
Squabble Over NEJM Paper Puts Spotlight on Antishock Drug http://news.sciencemag.org/scienceinsider/2012/08/squabble-over-nejm-paper-puts-sp.html
August 13, 2012
Fresenius Threatened to Sue Doctor over Study:
August 14, 2012
A Bloody Mess: Pharma, Legal Threats, and Fraud: http://neuroskeptic.blogspot.com/2012/08/a-bloody-mess-pharma-legal-threats-and.html
Would I sign now, knowing what I know now? Probably not.