Friday, April 14, 2006

The unfairness of Merck's current problems

I was reading Yahoo finance today and came upon this Reuters article: "Study shows how painkillers raise heart risk." At the top of this article was the banner " No spin. No agenda. Just the facts. As they happen."

Right, I thought.

However, this banner got me to thinking about the "spin" that has caused a proud pharmaceutical company to suffer the indignity of the VIOXX trial losses and accusations of impropriety, and events such as this, "Merck May Face Criminal Probe in New Jersey."

This is unbelievable.

While I worked at Merck, I can state will full confidence that people there, including the senior Merck Research Labs personnel I worked with, were both ethical and highly concerned about the safety of the products they produced. Dr. Ed Scolnick, for example, then president of Merck Research Labs, was a consummate clinician and scientist, and it was clear to me he would have chewed the head off anyone who dared even think to compromise on patient safety issues. I saw it personally, just with reference to matters of science. Dr. Scolnick had his ways.

Dr. Scolnick commissioned me to establish a web-based worldwide training program in scientific information retrieval, which I did, to bring all Merck scientists to a basic level of competence in information searching. He felt this essential towards good science, and that included safe science.

The issue of VIOXX is one of science, not of malfeasance. While I will not go into the issues of what should have or could have been reported to FDA, for example, I believe honest difference of opinion was involved in decision making, not malfeasance.

The only problem I believe Merck may have had was one of overconfidence, of resting on past laurels. As head of the Merck Research Labs libraries 2000-2003, I noted upon my debut that there were informatics tools (cheminformatics, science literature retrieval, etc.) that were not, in my view, adequately available. CAS SciFinder, for example, critical to basic and preclinical phases of discovery (at least), as well as MDL/Beilstein Crossfire, were not widely available to scientists.

SciFinder and the other computer databases have really gutted the rationale for committing large numbers of transformations to memory. It's important to know what sorts of things can be done, but there's little point in memorizing exactly which reagents do them and what journal they appeared in. You can always look that up, and when you do you'll likely find a dozen alternatives that you didn't even know about.
The CrossFire Beilstein* database is the world's largest compilation of chemical facts. As the cornerstone database to organic chemistry, the CrossFire Beilstein database is essential for generating new leads, planning synthetic routes (including starting materials and intermediates), determining bioactivity and physical properties and ascertaining the environmental fates of compounds.
I set out to convince my management that additional funds were needed to substantially increase access to these tools, using a detailed and comprehensive department-by-department analysis, testimonial from scientific leaders as to the critical nature of such access, and comparisons to competitors where access was greater. I received only about one third of what I sought from the VP who headed research computing (who had difficulty understanding the ROI), although in the end I obtained a global unlimited license to Beilstein and significant increase to SciFinder with the limited funds.

I believed then, and believe now, that this represented the effect of overconfidence. In the past, Merck's scientists had invented fantastic drugs without such tools. It was thought they could continue to do so. In reality I believe that the "low hanging fruit" were largely picked, and to move beyond them required new informational tools.

One other symptom of overconfidence was in the background of that VP who oversaw research computing. That person had no background in medical science. As I've pointed out in my writings, in biomedical computing a person's skills and abilities should match their position and authority. However, that is a matter of opinion, not of unchallengable fact. This issue culminated in the closure of one of the research libraries last year in the Rahway site in the belief that eJournals were sufficient, something I'd advised against when I was there, and which I found out about from displaced employees.

As an information scientist I had my views, and the decision makers theirs. Again, the VP's making the decisions simply had a different opinion from mine. These decisions were not made in any negative light.

It's likely any perceived problems related to VIOXX clinical trials adverse events were, at worst, due to this issue and nothing more.

I believe it is extremely unfair for issues related to honest opinion, however those opinions were driven, to be spun into stories about unethical practices. Merck's leadership and line personnel were all highly committed to patient safety. The current sad events represent the abuses of the tort system, with which physicians are all too familiar, and represent a severe loss to biomedical science and the innovation that companies like Merck are capable of when not confronted by legal manipulation.

We will all suffer for this.

-- SS


Anonymous said...

I'm not so sure. The crux of your argument seems to lie in the sentence :

"I believe it is extremely unfair for issues related to honest opinion, however those opinions were driven, to be spun into stories about unethical practices. "

The problem relates to an approach to science that leads to generation of this so called "honest opinion". Over two decades, pharmaceutical companies have ridden roughshod over fundamental principles of scientific enquiry such as proper access of scientists to unadulterated raw data. They have done this with the quiet acquiescence of governments and regulatory bodies. The fact that Merck's approach is perhaps no worse than that of other companies is irrelevant - they happen to have been burned as a result of the outcome and the fact that the tort system to which you refer has chosen to focus on this particular issue -- so be it.

1) There is incontrovertible evidence that work funded, supported and designed by pharmaceutical companies produces findings which are almost invariably in accordance with the desires of that company.

2) The reasons for this are complicated (ranging from subconscious selection of non-challenging study design to outright cheating). The exact reasons are irrelevant here.

3) Companies have to accept that if they allow a mode of science that is predicted to lead to predictable findings, they bear responsibility when those findings are incorrect.

4) The question then is whether science was conducted in a way that would have been predicted to lead to predictable outcomes. So one might ask for example whether:

a)In designing, presenting and publicising "science" did Merck recruit and pay predictable "thought leaders" or did they ask scientists to attempt falsification of Merck's desires (read Popper)

b) Did all academic authors and interested parties have full and proper access to raw data?

c) Did authors of work independently analyse all data?

d) Were academic authors encouraged to analyse data in a way that was designed to falsify rather than confirm preconceptions.

and so on....

Aubrey Blumsohn

InformaticsMD said...

The crux of your argument seems to lie in the sentence

The crux of my "argument" lies in the fact that I was there and know the principals. In fact, I am offering an opionion based on personal experience.

-- SS

Anonymous said...

The issue is probably much more complex.
May I suggest the reading of a thoughtful review of this issue in an article by D. Michaels entitled "Doubt is their product" Sci Am 2005;292(6):96-101.
One paragraph says:
"Uncertainty is an inherent problem of science, but manufactured uncertainty is another matter entirely. Over the past
three decades, industry groups have frequently become involved in the investigative process when their interests are
threatened. If, for example, studies show that a company is exposing its workers to dangerous levels of a certain
chemical, the business typically responds by hiring its own researchers to cast doubt on the studies. Or if a
pharmaceutical firm faces questions about the safety of one of its drugs, its executives trumpet company sponsored
trials that show no significant health risks while ignoring or hiding other studies that are much less reassuring. The
vilification of threatening research as "junk science" and the corresponding sanctification of industry-commissioned
research as "sound science" has become nothing less than standard operating procedure in some parts of corporate
Mayer Brezis, MD MPH
Professor of Medicine
Hadassah University Hospital