Rapid Responses to:
|
|
Rapid Responses: Rapid Responses published:
-
![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
Dictatorship of statistics, meta-analyses mess and sources of confusing conclusions
- AUGUSTO PIMAZONI (21 November 2007)
-
Don't shoot the messenger
- ARTHUR A. LEVIN MPH (8 December 2007)
-
Beyond any reasonable doubt
- AUGUSTO PIMAZONI, MD (11 December 2007)
|
|
|||
|
AUGUSTO PIMAZONI, Coordinator, Diabetes Education and Control Group - Kidney and Hypertension Hospital, UNIFESP, MED MARK Medical Marketing Consultants, Sao Paulo, Brazil
Send response to journal:
|
What is going wrong with clinical studies? What is going wrong with our renowned scientists that are still considered the last line of defense against the explosion of ignorance devastating the whole planet? What is going wrong with us, practicing physicians, who are no longer capable of correctly interpreting even the very basic clinical studies? What is going wrong with meta-analyses and the messing conclusions it yields? Who is to blame for the critical credibility crisis of medical sciences and for the sense of insecurity and uncertainty that promotes more confusion than conclusions? After all, what is going wrong with medical science as a whole? Statistics was once defined as the art and the science of proving whatever you want to prove. No matter how absurd your thesis might be there will always be a statistical method to help you prove your point. As a medical marketing consultant for the pharmaceutical industry in Brazil and Latin America, I once had the opportunity of producing in a same week two sets of arguments, pro and against cox-2 inhibitors, with totally conflicting conclusions but fully based on reliable articles and authors from the international literature. I did so in a very ethical way, without any guilt or ethical conflict, considering the scientific quality of the sources I used. Obviously, it would be impossible to carry out clinical studies without using statistics. But the extraordinary development of this branch of science produced a paradoxical side effect of complicating the planning and the interpretation of clinical studies to the extent of bringing much more fight than light to the medical science. Although considered level A in evidence based medicine, meta-analysis is now facing its most intense phase of lost credibility. Take the rosiglitazone affair as a sad example of the catastrophic effects of misguided selection and data misinterpreting. Quite a few different meta- analyses were conducted by different authors on this subject, leading to the most confusing and unreliable conclusions. Chances are that we might be crucifying an effective drug solely on the basis of statistical disputes with no bearing to the sacred medical truth. The arguments pro and against rosiglitazone are fully derived from conflicting results and conclusions of confusing and unreliable utilization of meta-analyses. AUGUSTO PIMAZONI, MD
Potential conflicts of interest: Medical marketing consultant for the pharmaceutical industry, but not a consultant for GSK. Competing interests: Medical Marketing Consultant to the Pharmaceutical Industry in Brazil and Latin America |
|||
|
|
|||
|
ARTHUR A. LEVIN MPH, DIRECTOR, CTR FOR MEDICAL CONSUMERS 239 THOMPSON ST NYC NY 10012
Send response to journal:
|
I am responding to Augusto Pimazoni's posting in which he complains about the confusion caused by those who believe that claims of effectiveness and safety made for pharmaceuticals should be based on evidence. In his response, the author cites the controversy over the safety of rosiglitazone and characterizes it as "sad" and with "catastrophic" effects." He anchors this rather stunning condemnation, in part, on the incorrect assertion that the conclusions of different meta-analysis were "most confusing and unreliable." I served as the consumer representative on the U.S. Food and Drug Administrations panel that heard the evidence about the cardiovascular safety of rosiglitazone (and was the lone vote to take it off the market). The results of three separate meta-analysis were presented; one by the sponsor, one by the FDA reviewers and of course, the one by Nissen and colleague published in the New England Journal of Medicine. All three arrived at more or less the same conclusion; that there was a suggestion rosiglitazone might pose excess CV risk. However, when the placebo- controlled studies were singled out, the evidence of CV risk turned out to quite robust. These results were confirmed a short time later by Furberg et al. I fail to understand how the significant relative risk revealed in the placebo studies can be characterized as "unreliable and most confusing." What evidence that a drug is unsafe would satisfy Dr. Pimazoni if such studies do not? What is truly "sad" about the rosiglitazone controversy is that clinician-specialists once again have shown their unwillingness to be guided in their practice by evidence that a popular, heavily marketed drug may be unsafe. Worse, if Dr. Pimazoni is any example, they want to shoot the messenger. Competing interests: None declared |
|||
|
|
|||
|
AUGUSTO PIMAZONI, MD, Coordinator, Diabetes Education and Control Group Kidney and Hypertension Hospital, Federal University of Sao Paulo, Brazil
Send response to journal:
|
This legal concept is fully applicable to scientific matters for the very simple reason that medical science should be guided by dispassionate and unbiased evaluation of available data and its implications are crucial to establish medical truth with the needed level of reliability. The drug approval and continuous evaluation processes must follow the principle that facts should be considered “beyond any reasonable doubt” to provide adequate grounds for the approval or withdrawal of a drug from the market. In response to Arthur Levine I have the following comments: 1-) First of all, unfunded criticism and personal innuendos do not belong to the healthy practice of democratic debate and is a factual demonstration of passionate, inappropriate and biased attitude towards the very basic ethical foundations that should guide the exchange of ideas and opinions about medical matters. And this is undebatable… 2-) Many meta-analyses can indeed be methodologically flawed because of threats such as combination of dissimilar studies, publication bias and inclusion of poor-quality studies (1,2). And this is undebatable… 3-) If the debatable conclusions of these meta-analyses were as strong as they intended to be, FDA, EMEA and other regulatory agencies around the world would have instantly withdrawn rosiglitazone from de market, as they did with many other drugs. To my knowledge this didn’t happen so far. And this is undebatable… To make a long story short, the concept of “beyond any reasonable doubt” is probably the most basic requirement for a wise decision on the issues surrounding the safety profile of rosiglitazone or any other drug: if proven guilty, this debate will be over. And this is undebatable… AUGUSTO PIMAZONI, MD
Competing interests: Medical Marketing Consultant for the Pharmaceutical Industry in Brazil and Latin America (Not a consultant for GlaxoSmithKline) Reference: (1) : “Applying a Meta-Analysis to Daily Clinical Practice”. Miser, WF, In: Evidence-Based Clinical Practice – Concepts and Approaches – Editors: Geyman, JP, Deyo, RA and Ramsey, SD. Butterworth Heinemann, 2000. Chapter 6, page 59. (2) : “Misleading Meta-Analysis: A Need to Look Beyond the Headlines”. Chaturvedi N. et al. Diabetic Medicine. DOI: 10.11 11/j.1464- 5491.2007.02139.x Competing interests: Medical marketing consultant for the pharmaceutical industry in Brazil and Latin America |
|||