Erick Turner, MD: Selective publication of positive trials on antidepressants

Interviewed and produced by Steven Greer, MD

Erick Turner, MD, psychiatrist at Oregon Health and Science University and former FDA medical officer reviewing psychotropic drugs, discusses his new England Journal of Medicine paper on the problem of selectively publishing only the positive trials on antidepressants and the failure of drug companies to publish the negative trials, thus skewing the body of literature.

 

The Yale led reanalysis of the BMP-2 InFuse trials

Interviewed by Steven E. Greer, MD

Medtronic granted rare access to a team led my Yale’s Harlan Krumholz and turned over the complete datasets on 17 InFuse (BMP-2) clinical trials. The goal was to determine whether adverse events being reported in real world usage were significant trends requiring new label warnings. Yale contracted Oregon Health and Sciences University to conduct one of the meta-analysis. We interviewed the lead author, Rongwei Fu, PhD.

Dr. Fu explains her findings. BMP-2 showed no efficacy advantage over other methods to fusing the spine, while also showing increased adverse event rates. In the cervical spine, their group concluded that BMP-2 was contraindicated.

Early breast cancer screening leads to false positives and overdiagnosis

Archie Bleyer, MD, radiation oncologist at the Oregon Health and Science University, discusses his NEJM paper that concluded early breast cancer screening using mammography led to more findings of false positives.

Roger Chou, MD: How the AHRQ creates and grades a meta-analysis

Produced and interviewed by Steven Greer, MD

A meta-analysis is the most influential form of systematic review now, but are all meta-analysis worthy of the highest level of quality in the hierarchy of the AHRQ? Are some meta-analyses “garbage in, garbage out”? Are there standardized, widely accepted, methods for going about a meta-analysis, or are the drug and device industries manipulating this process to create marketing junk science? Are academic doctors doing more meta-analyses because they end up being referenced by more journals and boost their CV?

In Part 1, Dr. Roger Chou of Oregon, a researcher for the AHRQ via a contracted Evidence-based Practice Center, and also a contributor to the U.S. Preventive Services task Force, discusses the rulebooks used by the AHRQ to go about systematic reviews of medical literature.

In Part 2, Dr. Chou discusses how they spot a bad meta-analysis and exclude it from their systematic reviews. He lists as a specific example of a sloppy meta-analysis.

Why the Oregon health experiment “failed”

In 1989, Oregon reformed their Medicaid program in part by using comparative effectiveness research to generate a prioritized list of services that they used to define covered benefits. The goal was to restrict wasteful or needless therapies (like spine surgery for uncomplicated low back pain) rather than restrict the number of people covered by health insurance. The plan eventually hit regulatory roadblocks, and Oregon was forced to limit the number of people covered after all. Critics subsequently dismissed the plan as a failed attempt at rationing health care.

Somnath Saha, MD, MPH, Chairman of the Oregon Health Services Commission and author of a recent Perspective in the New England Journal of Medicine on the matter, spoke with The HCC about lessons learned and what a national healthcare reform effort would need to do in order to allow an approach like Oregon’s to succeed.

In Part 2, Dr. Saha gives a primer on comparative effectiveness research.

Will 2010 be a depressing year for antidepressants?

January 7, 2010, The Healthcare Channel http://thehcc.tv/

Much as 2009 was a bad year for the spine surgery industry, has a critical mass of negative data on antidepressants been reached to make 2010 the year where prescription trends decrease? The current JAMA has an article that is making national news. In the paper by J. Fournier, et al, the conclusion was:

“True drug effects (an advantage of ADM over placebo) were nonexistent to negligible among depressed patients with mild, moderate, and even severe baseline symptoms, whereas they were large for patients with very severe symptoms…….

Prescribers, policy makers, and consumers may not be aware that the efficacy of medications largely has been established on the basis of studies that have included only those individuals with more severe forms of depression. This important feature of the evidence base is not reflected in the implicit messages present in the marketing of these medications to clinicians and the public. There is little mention of the fact that efficacy data often come from studies that exclude precisely those MDD patients who derive little specific pharmacological benefit from taking medications. Pending findings contrary to those reported here and those obtained by Kirsch et al and Khan et al, efforts should be made to clarify to clinicians and prospective patients that whereas ADM can have a substantial effect with more severe depressions, there is little evidence to suggest that they produce specific pharmacological benefit for the majority of patients with less severe acute depressions.”

The JAMA article recommends that policymakers be informed of the limited efficacy of antidepressants and reassess recommendations. Some specific examples of changes that could be made at the policy level would be raising the tier level in Medicare Part D, making the drugs more expensive to use, or a revaluation of the label indications by the FDA, just to name a few.

The New York Times discussion of the Fournier JAMA paper quotes Erick Turner, MD: psychiatrist and former medical officer for the FDA who evaluated antidepressants. The HCC interviewed Dr. Dr. Turner about a related matter whereby industry-funded studies supporting the efficacy of antidepressants were biased because the negative studies were never published in many cases.

In addition to the above, a prominent Senator is now on the case of antidepressant abuse.

Senator Benjamin Cardin (D-MD) is investigating the high usage rate of antidepressants in the military. In many cases, the medications are administered in unsupervised battlefields. Coinciding with this is the soaring rate of suicide in the military. The HCC interview with Senator Cardin may be viewed in the video player section.

In 2008 and 2009, Senators Grassley and Kohl addressed the biasing influences of drug industry payments to psychiatrists. Prominent psychiatrists at Harvard, Emory, Stanford and others have been reprimanded for concealing large payments from the makers of antidepressants. Moreover, if healthcare reform becomes finalized, the Physician Sunshine Payment Act will add more pressure on the ability for drug companies to create “thought leaders” promoting antidepressants.

The growth of total prescriptions for all forms of antidepressants has been stagnant. The HCC combined the Total RX data from IMS Health for the class of drugs including SSRI (Prozac, Zoloft, Celexa, Paxil, etc), SNRI (Effexor, Pristiq, Cymbalta, etc), and newer classes (Wellbutrin, etc).

Although an astonishing 200 Million prescriptions for antidepressants were written in 2008, growth has been nearly flat for the last three years (we have preliminary 2009 numbers of TRX being 208 Million). Of note, all prescription drug usage as a whole is also down with the economic depression.

	2004	2005	2006	2007	2008
Total RX all forms of antidepressants (000)	181,815	183,468	195,856	202,313	206,468
year over year growth		1%	7%	3%	2%
IMS health data

Is this indicative of a market close to imploding rather than growing? The HCC will be following these trends and developments in 2010. Stay tuned.