Forgive me, for sometimes I see humor in very serious issues. I developed a hyper-realist viewpoint a few years ago after reading Robert Greene and Joost Elffers' "
48 Rules of Power ", Machiavelli's
"The Prince" and Sun Tzu's
"The Art of War ," the latter in the context of a strategic management course.
The events related to Avandia seem to me a brilliant depiction of power relationships and natural incentives. The science is nearly irrelevant, except to the extent that it is used (or misused) as a function of an individual's or a group's natural incentives.
The whole thing started with
Steve Nissen's somewhat flawed meta-analysis of cardiovascular mortality associated with rosiglitazone [I will use the generic name from here on.]
The important feature of this article is that it raises questions about rosiglitazone, but does not answer them. Perhaps a little more substantial is the fact that he did not have access to original source data, because it is proprietary information owned and controlled by the pharmaceutical companies. To me, this is an important point that does not yet seem to have reached to the popular consciousness.
Does Dr. Nissen have an ax to grind? I don't know, but he certainly does have an interest in publication and the more controversial the information, the greater the attention and the greater the security of future grant money.
Valid point: Pharmaceutical companies insist on controlling and potentially suppressing clinical information about the drugs they wish to sell. This is natural and indignation is laughable.
Valid point: It is difficult, if not impossible to separate epidemiologically the contributions of CV disease from the contribution of the medication. A meta-analysis is probably not the best way to do it; it is hypothesis-generating, not hypothesis-proving. Meta-analysis is the most practical method of monitoring for safety. However, finding an association where it could reasonably have been expected is not newsworthy. Now, find me a causal chain based on real-world observation and I'll stand up and pay attention. I acknowledge this to be virtually impossible given the lack of openness in pharmaceutical research.
Valid point: Dr. Nissen took pharma money and published an anti-pharma article. Brilliant... somewhat dishonest, but brilliant. He publishes the following conflict of interest statement:
Dr. Nissen reports receiving research support to perform clinical trials through the Cleveland Clinic Cardiovascular Coordinating Center from Pfizer, AstraZeneca, Daiichi Sankyo, Roche, Takeda, Sanofi-Aventis, and Eli Lilly. Dr. Nissen consults for many pharmaceutical companies but requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor a tax deduction. No other potential conflict of interest relevant to this article was reported.
It is a natural incentive for a researcher to seek funds and then seek publication, so attempting to place restrictions on researchers is not going to work in the long run. This is natural and indignation is laughable.
The drug industry's response was to vilify him. This is a
Medscape summary of the academic wrangling .
This from Science Daily .
This from the WSJ Health Blog .
But the fact is that the science of
meta-analysis is difficult, arcane and beyond the understanding of most scientists and physicians . There are a half-dozen epidemiologists I would personally trust to help interpret this information for me, if I thought it was worth it. But there are better things to save my favors for.
In fact, this is a
political issue and the considerations include the pharmaceutical industry's profitability versus the cost of and safety of new medications. Is it any wonder that the industry responds in the blogs, the media and scientific articles with
their own counter-arguments - The most prominent of these spokesmen is Peter Pitts, so
his position is predictable in advance.
This too is natural and indignation is laughable.
Does it make sense to expect the FDA to be the absolute arbiter on the safety of medications? Probably not; there is a threshold that needs to be recognized, because no extraneous substance can be consumed with impunity by the entire population. If the disease for which one takes a medication causes the side effect in question, greater caution must be taken; the epidemiology is extremely complex. People with diabetes get heart failure and people with depression commit suicide. This is not a causal link and the association is unsurprising.
So why the confusion? Follow the money:
- New medications are expensive for payers.
- New medications are profitable for the pharmaceutical industry.
- Physicians are susceptible to being style-mongers and trend-followers like anybody else; why not try the new and sexy drug?
- Impugning the safety of a new drug is an easy way to reign in the potential of over-prescribing and the unrealistic expectations bred by pharmaceutical marketing.
- The pharmaceutical industry has an interest in protecting their margins and their franchises.
- The research industry [yes, I said industry] has an interest in attracting attention for its research and securing future funding.
- The news industry is always looking for a new and sensational headline; "New Drug Risking Millions of Lives" is a great headline. The hair-splitting required of scientific reasoning does not make good copy.
- And then, there's the ambulance chasers... see the links at this blog post . Isn't this what it's all about?
I love this country because it is the balance of these lobbies and special interests that will determine what the regulation. For those who believe that there is an objective principle, such as truth, beauty or justice that will define our legislative and regulatory response, I applaud your "goodness."
But the naivety gets nobody anywhere.
The events related to Avandia seem to me a brilliant depiction of power relationships and natural incentives. The science is nearly irrelevant, except to the extent that it is used (or misused) as a function of an individual's or a group's natural incentives.
The whole thing started with Steve Nissen's somewhat flawed meta-analysis of cardiovascular mortality associated with rosiglitazone [I will use the generic name from here on.]
The important feature of this article is that it raises questions about rosiglitazone, but does not answer them. Perhaps a little more substantial is the fact that he did not have access to original source data, because it is proprietary information owned and controlled by the pharmaceutical companies. To me, this is an important point that does not yet seem to have reached to the popular consciousness.
Does Dr. Nissen have an ax to grind? I don't know, but he certainly does have an interest in publication and the more controversial the information, the greater the attention and the greater the security of future grant money.
Valid point: Pharmaceutical companies insist on controlling and potentially suppressing clinical information about the drugs they wish to sell. This is natural and indignation is laughable.
Valid point: It is difficult, if not impossible to separate epidemiologically the contributions of CV disease from the contribution of the medication. A meta-analysis is probably not the best way to do it; it is hypothesis-generating, not hypothesis-proving. Meta-analysis is the most practical method of monitoring for safety. However, finding an association where it could reasonably have been expected is not newsworthy. Now, find me a causal chain based on real-world observation and I'll stand up and pay attention. I acknowledge this to be virtually impossible given the lack of openness in pharmaceutical research.
Valid point: Dr. Nissen took pharma money and published an anti-pharma article. Brilliant... somewhat dishonest, but brilliant. He publishes the following conflict of interest statement:
It is a natural incentive for a researcher to seek funds and then seek publication, so attempting to place restrictions on researchers is not going to work in the long run. This is natural and indignation is laughable.
The drug industry's response was to vilify him. This is a Medscape summary of the academic wrangling . This from Science Daily . This from the WSJ Health Blog .
But the fact is that the science of meta-analysis is difficult, arcane and beyond the understanding of most scientists and physicians . There are a half-dozen epidemiologists I would personally trust to help interpret this information for me, if I thought it was worth it. But there are better things to save my favors for.
In fact, this is a political issue and the considerations include the pharmaceutical industry's profitability versus the cost of and safety of new medications. Is it any wonder that the industry responds in the blogs, the media and scientific articles with their own counter-arguments - The most prominent of these spokesmen is Peter Pitts, so his position is predictable in advance. This too is natural and indignation is laughable.
Does it make sense to expect the FDA to be the absolute arbiter on the safety of medications? Probably not; there is a threshold that needs to be recognized, because no extraneous substance can be consumed with impunity by the entire population. If the disease for which one takes a medication causes the side effect in question, greater caution must be taken; the epidemiology is extremely complex. People with diabetes get heart failure and people with depression commit suicide. This is not a causal link and the association is unsurprising.
So why the confusion? Follow the money:
- New medications are expensive for payers.
- New medications are profitable for the pharmaceutical industry.
- Physicians are susceptible to being style-mongers and trend-followers like anybody else; why not try the new and sexy drug?
- Impugning the safety of a new drug is an easy way to reign in the potential of over-prescribing and the unrealistic expectations bred by pharmaceutical marketing.
- The pharmaceutical industry has an interest in protecting their margins and their franchises.
- The research industry [yes, I said industry] has an interest in attracting attention for its research and securing future funding.
- The news industry is always looking for a new and sensational headline; "New Drug Risking Millions of Lives" is a great headline. The hair-splitting required of scientific reasoning does not make good copy.
- And then, there's the ambulance chasers... see the links at this blog post . Isn't this what it's all about?
I love this country because it is the balance of these lobbies and special interests that will determine what the regulation. For those who believe that there is an objective principle, such as truth, beauty or justice that will define our legislative and regulatory response, I applaud your "goodness."But the naivety gets nobody anywhere.