Saturday, May 31, 2014

The Top Five Ways that Pharma Affects You recently published a piece:
--that cuts to the chase in the ways that the media can either bring us up to date or else pull the wool farther over our eyes.

The main thrust of the piece is a review of the five most common ways that the pharmaceutical industry manipulates physicians and keeps things favorable to their own goals--which means, replacing what's true with what's valuable. The five ways are no surprise to anyone, but as we increasingly get into the thick of the swamp, it's valuable to be reminded of the big picture every so often:
  • Spying on prescribing
  • Easy CME access for shilling docs
  • Ghostwriting
  • Speakers' bureaus
  • Clinical trials (how the enterprise is conducted so that who pays the piper calls the tune, when at least 70 percent of the piper is paid by Pharma)
It's valuable at times to recollect certain aspects of the big picture. Take ghostwriting. The main features of the extent of medical ghostwriting, how as many as half the stories in med journals on some sensitive topics might be ghostwritten, have been out for at least 10 years. What has happened? About zilch. Everyone agrees that ghostwriting is an especially egregious offense, and so far as I can tell, it goes on just about as before. Ditto for most of the other sins.

In another smart move:
--the BMJ ran a study of the current state of the publication of clinical trials. Not surprisingly, there was disagreement over most issues. But at least there was finally a sense that something was starting and that the end results might be useful.

We're getting out toward a decade from the publication of the first wave of studies that started to shed light on the real implications of Pharma's rigid control over the system. What's changed? To a large extent, nothing.

Wednesday, May 14, 2014

Are KOLs drying up? Praise be

Back in 2011 I heard from Cutting Edge Information on the subject of key opinion leaders (KOLs):
I figured that once I outed them on this blog, they would know better than to send me any more e-mails, but apparently they are still at it; the cold-call e-mail that’s reprinted below arrived this week. The content would seem to suggest that Pharma firms are having greater difficulties finding “Key opinion leader” physicians (aka shills) due to the increased transparency requirements of the pending Sunshine Act. If this is the case, then of course it is what I have been advocating for years. I read both the e-mail and the attached detailed brochure but could not find a figure as to the actual cost of this 179-page report, so you’ll have to contact Cutting Edge Information directly if you want to buy a copy. (I have a feeling there might be some sticker shock…)

Unsolicited E-mail message:


Key opinion leading physicians face pressure from increasing transparency via the Sunshine Act and organizational restrictions on pharma-physician relationships. Has your organization made the strategic, resource and operational shifts necessary to compete for KOL services in this new environment?

Cutting Edge Information worked closely with senior-level medical and KOL management executives at more than 30 leading pharmaceutical and biotech companies to distill the latest strategies, benchmark data, executive insights and best practices that are enabling the top-performing KOL management organizations to continue to achieve results for their companies in our new report, “Pharmaceutical Key Opinion Leader Management: Effective Strategies for Segmenting Thought Leaders.” Use this report to:

• Benchmark extensive, deep thought leader segmentation data and analysis
• Prepare your KOL management team(s) to combat shrinking KOL pools
• Leverage third-party vendors’ expertise to develop and refresh robust thought leader directories
• Reach beyond traditional specialist KOLs to fill out thought leader listings
• Compare your company’s organizational structure, staffing and budget support to those of your peers and competitors

I have attached a summary document with more details about this new report for your review. I would appreciate the opportunity to answer your questions about how this report will be of value to you and your organization. Please call me directly at +1-919-433-0211 or reply by email. I look forward to hearing from you soon.

Pharmaceutical Key Opinion Leader Management: Effective Strategies for Segmenting Thought Leaders
Pages: 178
Data Charts/Tables: 95+
Metrics: 500-plus
Companies Consulted: more than 30, including Boehringer Ingelheim, CSL Behring, Ferring, Novo Nordisk and Sanofi


For more information on any of our other medical affairs reports below, please reply by email and I will be happy to send a brochure:

1. Pharmaceutical Advisory Boards: Uncovering Clinical, Market and Payer Insights to Enrich Product Opportunities
2. Promotional Speaker Programs: Successfully Managing Speaker Bureaus and Recruiting Thought Leaders
3. Educational Speaker Programs: Medical Event Management and Recruitment in a Complex Regulatory Environment
4. MSL Activities and Performance Measurement: Harnessing KOL Relationships for Optimal Clinical Support
5. Managing MSL Teams: Budget, Staffing and Compensation Benchmarks
6. Medical Information Teams and Call Center Management

Kind Regards,

Jon Hess
Account Executive, Cutting Edge Information
1000 Park Forty Plaza, Durham, NC 27713
O: (919) 433-0211 | F: (919) 433-0220 |

Monday, May 5, 2014

The Ongoing Statin Debate, or Is It?

Those of you who are heartily sick of my talking about statins, please skip this post.

By way of joining in on the controversial new statin guidelines:
--the New England Journal offered in their April 24 issue a debate over the guideline recommendations. Three authors were assigned to take positions on a hypothetical 52-year-old male smoker with a normal cholesterol and LDL level (subscription required):
  • Do not treat with statins: Dr. Benjamin J. Ansell
  • Treat with statins and monitor LDL levels: Dr. Samia Mora
  • Treat with statins but do not monitor LDL: Dr. Harlan M. Krumholz

OK, so this sounds at first like one person taking the position I have argued for in this blog, and two others taking positions more favorable to the drug manufacturers. But things may not be quite as they seem.

Dr. Ansell does indeed argue against statins, using arguments we've reviewed previously, and noting the much bigger bang for the buck with lifestyle interventions, notably smoking cessation. But Drs. Mora and Krumholz don't dispute the importance of lifestyle--indeed you could say that we have here three arguments, all in favor of pushing lifestyle modification as the first step.

Dr. Mora makes out his favorable case for statin treatment and monitoring LDL by selecting some studies that seem to him to support this approach, but his concern seems to be that by closely watching LDL levels, the physician might find a low dose of statin that reduces risk sufficiently while avoiding the potential adverse effects of statins. So at least one of the "statin advocates" in this debate admits that statins can be harmful and should be used in lowest possible doses.

Dr. Krumholz is not really advocating for statins at all, it seems, but rather for patient choice and shared decision-making. And what information would he give the patient for this purpose? He'd stress that 50-60 people like this patient would have to be treated with statins for 10 years for a single one of them to avoid having a heart attack. He says that if he told the patient this, and the patient still wanted to take statins, he'd prescribe them--certainly a reasonable choice in my view.

In short, even the debaters that supposedly take the pro-statin positions in this "debate" actually have more negative things to say about statin therapy than the title would suggest.

D'Agostino RB, Ansell BJ, Mora S, Krumholz HM. The guidelines battle on starting statins (clinical decisions). New England Journal of Medicine 370:1652-1658, April 24, 2014.

Yet More Corruption in Pharma

Once again I'll move over and give the floor to Dr. Roy Poses at Health Care Renewal:

In the past, also following Dr. Poses' lead, I have blogged about corruption in the pharmaceutical industry:

This new post reviews five recent cases in which  drug companies have paid out large settlements in Federal court actions. While one or two of the cases mainly deal with financial wrongdoing (such as price-fixing), most have implications for the safety and quality of drugs supplied to patients. In none of these cases were any individuals working for the companies assigned any blame--Dr. Poses suggests that, since the whole purpose of most of the skullduggery was to make more money for the company, it is likely that instead a number of primary actors earned big bonuses. He then reminds us of the basic definition of 'corruption'--using one's power and position for personal gain. By this definition the behavior of these corporate executives was clearly corrupt.

And yet, for some reason, we think it impolite and indelicate to use such terminology in describing the behavior of U.S. corporations and their leaders. Dr. Poses suggests, and I agree, that it's time for this false delicacy to end.

Sunday, May 4, 2014

What Dead Salmon Are Thinking--and How That Relates to Drug-Industry-Sponsored Research

The Hastings Center Report, a prominent bioethics publication, published a special supplement (March/April 2014) on "Interpreting Neuroimaging," which contained an especially useful article by Dr. Martha J. Farah of the University of Pennsylvania Center for Neuroscience and Society. (If you want to know what this has to do with the topic of this blog, hang in with me for a little bit.)

What Dr. Farah is basically up to here is finding a middle course between extreme advocates of the new wave of neuroimaging studies in psychology, who claim incredible insights into human brain function and thinking, and extreme critics, who attack these findings as nothing but misguided statistical manipulations and artifacts.

I'm especially grateful to Dr. Farah's article because it referred me to a fascinating paper by a group of psychologists led by Craig M. Bennett of UC-Santa Barbara:

Dr. Bennett and colleagues are concerned about one particular error that they believe is all too common in the neuroimaging field (with around a quarter of papers in widely cited journals exhibiting the error at the date the article was written). A typical functional magnetic resonance (fMRI) scan of the human brain gathers data on 130,000 units of activity and makes many tens of thousands of comparisons. When we set the standard for statistical significance at the traditional p < 0.05, we accept that there's a 1-in-20 chance that any comparison that produces a positive result could do so by chance rather than because of a true causal link. When there are tens of thousands of comparisons, then a 1-in-20 chance produces an incredibly large number of findings that are actually due to random noise.

Bennett and colleagues recommend two particular statistical tests to avoid this problem, that are especially designed to address the way these large data sets behave. By contrast, the way some investigators typically try to resolve the problem is to set the bar higher for statistical significance, such as p < 0.001. There are so many comparisons in a typical fMRI study that this method, say Bennett et al., that this ploy does not work reliably.

They chose to demonstrate what they are talking about by setting up a parody of a real psychological study, in which a human subject is put in an MRI machine, shown photos of people in social interactions, and then asked to imagine what emotions those people must be experiencing. In their experiment, the subject was a dead salmon (about 18 inches long). They put the salmon in the MRI machine, told it what to do when looking at the photos, and then scanned its brain.

When they processed the scans in the usual way, they found two areas of heightened activity, in the dead salmon's middle brain and upper spinal cord. When they set the higher threshold for statistical significance, they still found these two areas of supposed activity. When they used instead the corrections that they recommended, there was no significant brain activity recorded. Bennett et al. concluded that unless you use the right statistical approaches, it was easy to get spurious results from brain scans.

As I read this study, I was reminded of one of the themes we've previously discussed many times in this blog--how industry-sponsored studies can be doctored to make new drugs look better than they are. One way we've seen this done is--you guessed it--multiple comparisons. If you look at enough different variables in the drug vs. placebo group, by chance, one is likely to be favorable to the drug. If you can spin the study to pretend that that particular measure was the one you were really interested in all along (instead of something you just happened to trip over when you analyzed the data at the end of the study), you can make a study sound impressively positive.

Bennett and colleagues mentioned in passing another statistical flaw that is not addressed by their favored methods, a form of circular reasoning. Because there are so danged many regions of the brain all firing off at various times, most of which have nothing whatever to do with the process psychologists want to investigate, it is tempting to use some statistical tools up front to narrow the field of vision to look only at the brain regions thought most likely to be informative. If one is not careful, one may then use the same statistical tools to decide that the information gleaned from those regions is of significance. (This is a variant of the classic joke about the drunk looking for his lost quarter under the lamppost because the light's better there.)

That trick, too, we have frequently seen in industry-sponsored pharma research. The major tools used are run-in and wash-out periods before the start of the formal data gathering. The pre-trial manipulations are designed to eliminate those subjects who respond too well to the placebo, or those who don't respond well to the drug, or other things the researcher does not want to see. This helps assure that when the "study" begins, the scale has already been tipped in the direction of the drug looking better than it really is.

Dr. Farah admits that neuroimaging data can be spun in incorrect ways due to insufficient attention to these statistical booby traps, but she immediately adds that this does not make neuroimaging research unique (or uniquely unreliable when done well). She gives examples from other fields of research where the same statistical flaws can be found.

She did not mention pharmaceutical clinical trials.  But she could have.

Bennett CM, Baird AA, Miller MB, Wolford GL. Neural correlates of interspecies perspective taking in the post-mortem Atlantic salmon: an argument for proper multiple comparisons correction. Journal of Serendipitous and Unexpected Results 1: 1-5, 2010. (Note: for people suspicious that the dead salmon paper is nothing by a hoax, there does indeed appear to be a journal of this title; and one would think that someone as familiar with the neuroscience field as Dr. Farah would know if the paper was phony. For more on the "study" see: