More on Guinea Pigging--The Quality of Pharmaceutical Research

Two longish articles by our old friend Dr. Carl Elliott and by Peter Aldhous:
https://medium.com/matter/did-big-pharma-test-your-meds-on-homeless-people-a6d8d3fc7dfe
https://medium.com/matter/why-are-dope-addicted-disgraced-doctors-running-our-drug-trials-aff6d20843bf
--raise interesting questions about clinical research on pharmaceuticals.

Dr. Elliott addresses the selection of subjects for research on new drugs, and shows that in many instances, they are taken from places that raise suspicions about the quality of the research--such as homeless  shelters, and other places that have a high incidence of mentally ill. Aldhous looks at the credentials of the physicians who do this research and shows that some cases, the physicians have been disciplined for serious violations.

Perhaps the best short summary of these two pieces appears toward the end of the Aldhous piece:

"Some experts agree that the FDA's entire rulebook for clinical trials, with its talk of things like 'institutional' review boards, reflects the academic past of clinical research--not today's industrial juggernaut of for-profit clinical trials firms and for-hire review boards, which oversee a workforce of doctors drawn from regular medical practice. 'They are regulations for a world that doesn't exist anymore,' says Elizabeth Woeckner, president of Citizens for Responsible Care and Research, which campaigns for the safety of medical research volunteers."

Therefore, when one reads that scientists have tested new drugs on patients and have yielded the following information, one has to wonder, first, whether those "patients" actually have the diseases the scientists are studying and have honestly reported their status (as opposed to making up what seems most fitting for payment for inclusion in the study, and getting away alive afterwards); and second, whether those "scientists" are properly trained physicians and can observe the variables required. There seems little concern, presently, to reassure the public that either is the case.

Rating New Hepattits Drugs: What Standard?

There seem to be two problems with the newest drugs for hepatitis C,  simeprevir (Olysio) and sofosbuvir (Sovaldi). The problem most discussed these days is "miracle drugs cost too much." For example, guru David Blumenthal, MD, holds forth on the Commonwealth Fund website--
http://www.commonwealthfund.org/publications/blog/2014/jul/drugs-and-dollars?omnicid=EALERT526507&mid=brody@msu.edu
--that Sovaldi is "dramatically effective and extraordinarily expensive." Robert Steinbrook and Rita F. Redberg, in an editorial in JAMA Internal Medicine, declare the new drugs "a scientific triumph". They then go on to note the problem--that Sovaldi can cost $1000 per tablet for 12 weeks' treatment, putting the cost at $84,000 ($168,000 for 24 weeks).

Our old friend Dr. Roy Poses at Health Care Renewal seems to be one of the few who's discussing a radically different problem--"maybe the drugs that cost so much are not miracle drugs at all." In his latest post: http://hcrenewal.blogspot.com/2014/07/sovaldi-quantum-leap-backwards-to-days.html--
he highlights the most recent article in JAMA, which is fawned over in an accompanying editorial despite the fact that it's non-randomized and non-controlled. Dr. Poses points out that the FDA decided to approve Sovaldi as a "breakthrough drug" which seems to have undercut the requirements that it be documented by something akin to science.

The article that accompanied the editorial in JAMA Internal Medicine addressed an evidence report by the Institute for Clinical and Economic Review, Boston, prepared for a meeting of the California Technology Assessment Forum. They concluded a need for caution regarding the two newest drugs:
"First, the evidence base on the comparative clinical effectiveness of these 2 new drugs remained thin in most areas and notably incomplete in others. For example, in some subgroups, such as patients who have failed earlier treatments, there were little or no data available. There were no long term data demonstrating the durability of short-term sustained virologic response rates for either drug; nor had either drug been compared head-to-head in a randomized clinical trial with each other or with a first-generation direct-acting antiviral drug. Finally, the evidence necessary for sofosbuvir to gain marketing approval through the FDA’s breakthrough designation was particularly sparse and did not include requirements for controlled trials." They noted that as a result of this presentation, the California forum voted the use of these drugs a "low value" for the health system.

Steinbrook and Redberg noted that Sovaldi had grossed $2.3B in the first quarter of 2014. So "low value" by one standard seems to be pretty high value by another. If the past is any indication, it will be some years before we find out which standard is the correct one; and meanwhile, the profiteers at the makers of the two drugs can expect a killing.

Steinbrook R, Redberg RF. The high price of the new hepatitis C virus drugs. JAMA Internal Medicine 174:1172, 2014.

Ollendorf DA, Tice JA, Pearson SD. The comparative clinical effectiveness and value of simeprevir and sofosbuvir for chronic hepatitis C infection. JAMA Internal Medicine 174:1170-71, 2014.





   

USA: Worse than Two Countries in Health Costs

Every so often, it’s worth taking a look at how badly we’ve allowed ourselves to distort reality. We generally think that health care costs in the U.S. are about what they are in the rest of the world, or maybe just a bit worse. We seldom allow ourselves to see the true state of affairs. Accordingly, when a wake-up call comes along like the recent announcement from the Commonwealth Fund:
http://www.commonwealthfund.org/publications/fund-reports/2014/jun/mirror-mirror?omnicid=EALERT495214&mid=mh@cmwf.org
--we either don’t know what to do with it at all, or quickly look for someplace to hide.

A while ago, I was glancing at a talk given by Michael Fine, head of public health in Rhode Island. He made the interesting point that health care in the U.S., calculated on a per capita basis, costs more than it does in the United Kingdom and Japan. Let me be very clear about this: The average annual cost of health care, per person, in the UK, plus the average annual cost of health care, per person, in Japan, is less than the cost of health care, per person, in the U.S.

Maybe a few Americans have an idea that health care costs more in the U.S. than elsewhere, and that we actually get less for what we spend here than elsewhere. But I rather doubt that most Americans realize just how bad it is—that people in two other advanced nations of the world pay as much as we do per person (actually, not quite so much) for health care.

I was reminded of these figures thanks to the Commonwealth Fund’s handy reminder. They don’t include Japan in their list of 11 countries, but they give several other examples. You can assemble the figures for “almost as much as the U.S. spends on health per person per year” in several different ways:

The U.K. or Sweden or New Zealand or Australia

Plus

Canada or France or Germany

Either approach would come in less than the U.S., which tops all of the countries at $8508 per person per year. The next highest country is Norway, far back at $5669. (The first batch of countries I picked all spend between $3000 and 4000 per person per year; the second set spend between $4000 and $5000.)

The remainder of the report is not terribly auspicious for the U.S. America often spends the most money and gets the worst results. A few areas show some modest improvement since the last time the people looked, but generally things are down in the cellar and mostly staying there.

For many decades we have been used to hearing that the U.S. has “the best health care system in the world.” This has pretty much gone by the boards, though we’ll still find some dumb politico repeating it occasionally. But how far we have sunk from that status is not seen clearly by the vast majority of citizens.

Pharmaceutical costs play a relatively small role in the excessive costs of U.S. health care, making up only about 10 percent of American total health care costs. But the average American has no idea whatsoever of how incredibly pricey American health care is, compared to any other country.

The Top Five Ways that Pharma Affects You

Salon.com recently published a piece:
http://www.salon.com/2014/01/25/5_evil_ways_the_multi_billion_dollar_drug_industry_is_in_bed_with_your_doctor_partner/
--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:
http://blogs.bmj.com/bmj/2014/05/30/jane-feinmann-is-the-current-system-of-publishing-clinical-trials-fit-for-purpose/
--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.

Are KOLs drying up? Praise be

Back in 2011 I heard from Cutting Edge Information on the subject of key opinion leaders (KOLs):

http://brodyhooked.blogspot.com/2011/06/keeping-kols-fat-and-sassy-these.html

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:

Howard,

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.


REPORT SUMMARY:
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


ADDITIONAL MEDICAL AFFAIRS REPORTS:

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
Jon_hess@cuttingedgeinfo.com | www.cuttingedgeinfo.com

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:
http://brodyhooked.blogspot.com/2013/11/new-cholesterol-guidelinesthe-devil-in.html
--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:
http://hcrenewal.blogspot.com/2014/04/the-pervasiveness-of-health-care.html

In the past, also following Dr. Poses' lead, I have blogged about corruption in the pharmaceutical industry:
http://brodyhooked.blogspot.com/2013/07/the-corrupt-us-health-system-and.html

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.