Disease Specific Survival vs. All Cause Mortality



The outcome for studies that look at mortality should be all cause mortality rather than disease specific or recurrence free mortality.  This is most often done wrongly in studies of treatments for cancer.  This allows bias to occur because death due to causes other than the disease being sought may still be related to that disease.  A recent study of Nesiritide, a natiuretic peptid, for the treatment of heart failure is an excellent example.  It concluded that cardiovascular mortality was the same in the treatment and control groups because the difference (increased mortality in the treated group) was small and didn't reach statistical significance.  (This of course goes against the aphorism; "failure to find an effect is not the same a lack of an effect".)  However, several of the patients that died of "non cardiovascular deaths" were not reported and could have died of a heart problem leading to another problem.  One subject who died of carbon monoxide poisoning may have had an arrhythmia while in her car and died when she sat there for hours without turning off the engine.  Another died in an automobile accident that may have occurred because they blacked out leading.



This leads to some comments on the interchange about "Big Pharma".  I think that there are two big issues to keep in mind.  "Big Pharma's" primary responsibility is to its shareholders.  The issues mentioned by Phil Hall all relate to the fiduciary responsibility that "Big Pharma" has to its shareholders.  Therefore, we should not be surprised that "Big Pharma" does not want studies that might show their drug is no better than current drugs on the market (i.e. "Me too drugs") and they don't want to do studies comparing their drugs to dirt cheap interventions (like generic drugs off patent).  However, the health care system has its primary obligation to its customers/clients/patients.  [At least the last time I looked I thought that we were still beholding to these people, but I might be wrong since the Bush administration market approach to medicine seems to be making us more responsible to shareholders.  Please forgive the diversion but I hope that you understand my point.]



Therefore, it seems that the pharmaceutical companies must be made responsible for supporting the social agenda of medicine, which physicians have allegedly or supposedly been doing all their careers.  This means that regulations must require "Big Pharma" to do either contribute 'blindly' to the dollars funding research or do the right type of studies themselves.  Without this we are pretty much at the mercy of poor science and the evidence obtained from tainted studies will always be of inferior quality.  It is up to the government (through the will of the people?) to regulate "Big Pharma" and the research agenda.  However, it is up to the individual clinician/health care worker to understand when she should and should not be using particular drugs because of their alleged benefit based on various types of "rigged studies."  It is only by having a solid foundation in EBM that physicians will be able to recognize when this happens and that's what we are all about.



Best wishes,



Dan



(Disclosure: The writer of this email is a dues paying member of "No Free Lunch", a non-profit organization that attempts to educate physicians on the dangers of too close associations with the pharmaceutical companies.   He receives no remuneration from this.)





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Dan Mayer, MD

Professor of Emergency Medicine

Albany Medical College

47 New Scotland Ave.

Albany, NY,  12208

Ph; 518-262-6180

FAX; 518-262-5029

E-mail; [log in to unmask]

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>>> Philip Hall <[log in to unmask]> 3/9/2006 11:27 AM >>>

This interchange and its "Big Pharma" riff suggests other variations on the original theme of "Best of..."



One is that perhaps we should all remember Voltaire's "The best is the enemy of the good." (Le meilleur est l'ennemi du bon.)



Another - Whatever the percent of research and publication that has no pharmaceutical backing, there are diverse reasons. One may be the most obvious, that the issue has little or nothing to do with Rx treatment. Alternatively, the pharmaceutical agent concerned may be so inexpensive to make that little to no profit is projected, or even cost recovery of research investment. It has been suggested that one reason that peri-conception folic acid prophylaxis against neural tube defects  has been so slow to penetrate public knowledge and behaviour is that no pharmaceutical company can afford to invest in its advertising as the stuff is so cheap to produce. In contrast, just about every pregnant woman in the northern hemisphere has been convinced that they need "prenatal vitamins", regardless of diet and personal circumstances, and their care providers probably believe so as well. But the evidence suggests that all that results in for most of them is expensive urine. Why the difference? Profit and marketing. 



At least in Canada, regular strength "ASA" can be bought cheaper than borscht. Not so for "mini" strength though, now widely marketed for prophylaxis in middle aged types such as myself for fatal MI prophylaxis. 81 mg, even in bulk, costs much more than 325 mg and cleverly, nobody is producting the latter in tabs that can be broken into quarters. Why the difference? Profit and marketing. 



In counterpoint, there are consistent undertones in this string and elsewhere that pharmaceutical companies are intrinsically evil. Consider what John le Carré did with this theme in The Constant Gardener, ramped up in the Hollywood-ized version, Oscars and al. I am not sufficiently naive to suggest that for profit motivation whether in drug production or anywhere else does not corrupt motives and practices. Vigilance, including self-vigilance, by all means. But season it with reason. Not all pharmaceutical companies, even the big ones, have plants located on the moral outskirts of Bhopal.



Phil. Hall

Winnipeg, Manitoba, Canada 

(Manitoba partially funded, and Winnipeg had two brief scenes in Constant Gardener, and  Capote was filmed completely here, for readers' unlikely interest)

(and Brokeback Mountain was filmed in Alberta)

 

>>> Paul Glasziou <[log in to unmask]> 3/9/2006 12:56 AM >>>

Dear Martin,

Good question. The pharmaceutical companies do 

invest *much* more in research than government 

and not-for-profit groups (in the UK this is 

about 5:1). However, often the research is me-to 

or marketing research that doesn't answer our 

clinical questions. So the research relevant to 

clinicians may be better balanced. I can't tell 

you how many of the 20,000 new randomised trials 

published each year are non-pharmaceutical 

interventions, but in a review of things we 

picked for the EBM journal we found about a 50:50 

split over 3 years. The split we found is similar 

to the split you can find in Figure 3 of a recent 

UK analysis of non-commercial trials:

Chalmers I, Rounding C, Lock K. Descriptive 

survey of non-commercial randomised controlled 

trials in the United Kingdom, 1980-2002. BMJ. 2003 Nov 1;327(7422):1017.

Cheers

Paul Glasziou







Philip F. Hall, MD BScMed FRCSC

Professor, Faculty of Medicine, University of Manitoba

Director, Fetal Assessment, Manitoba Obstetric Outreach and Maternal-Fetal Medicine Programs

President of Medical Staff

St.Boniface General Hospital, 409 Tache Avenue D2044

Winnipeg, Manitoba, Canada R2H 2A6

ph 204-237-2547 FAX 204-233-1751

(Past Chair, Obs & Gyn Specialty Committee,

Royal College of Physicians & Surgeons of Canada)



<www.umanitoba.ca/womens_health>







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