1 Boring Old Man

Tripartite Conflicts of Interest and High Stakes Patent Extensions in the DSM-5

by Cosgrove L. · Krimsky S. · Wheeler E.E. · Kaitz J. · Greenspan S.B. · DiPentima N.L.a

Psychotherapy and Psychosomatics. 2014 83:106-113.

[full text on-line]

Background: The revision process for and recent publication of the DSM-5 initiated debates about the widening of diagnostic boundaries. The pharmaceutical industry had a major financial stake in the outcome of these debates. This study examines the three-part relationship among DSM panel members, principal investigators [PIs] of clinical trials for new DSM-5 diagnoses, and drug companies.

Methods: Financial conflicts of interest [FCOI] of DSM panel members responsible for some new diagnoses in the DSM-5 and PIs of clinical trials for related drug treatments were identified. Trials were found by searching ClinicalTrials.gov. Patent and revenue information about these drugs was found using the US Food and Drug Administration’s Orange Book and manufacturer Annual Reports.

Results: Thirteen trials met inclusion criteria [testing drugs for some new DSM disorders]. Sixty-one percent of the DSM Task Force members and 27% of Work Group members reported FCOI to the trial drug manufacturers. In 5 of the 13 trials [38%], PIs reported ties other than research funding to the drug manufacturer. In 3 of the trials [23%], a PI had financial ties to the drug manufacturer and was also a DSM panel member who had decision-making authority over the revision process.

Conclusions: These findings suggest that increased transparency [e.g., registration on ClinicalTrials.gov] and mandatory disclosure policies [e.g., the American Psychiatric Association’s disclosure policy for DSM-5 panel members] alone may not be robust enough strategies to prevent the appearance of bias in both the DSM revision process as well as clinical decisions about appropriate interventions for DSM disorders.

A Pill for Every Ill

Newsweek

By John Ericson

February 6, 2014

[full text online]

… When the APA released the fifth edition of its manual in May 2013, it was instantly criticized by several researchers and clinicians, who claimed that some of the revisions and modifications reflected the agenda of an editorial panel that did not have the public’s best interest in mind. For example, many therapists and parents denounced the decision to define Asperger’s syndrome as a part of the autism spectrum rather than a stand-alone diagnosis. Some said it would skew statistics. Others said it would mess with identities…

… That, however, wasn’t the biggest concern. Other experts, including Sheldon Krimsky, professor of Urban & Environmental Policy & Planning at Tufts University, have pointed out that changes to the DSM can also be big business, with lots of downstream profit for everyone involved. If, for example, the DSM-5 finds a new "indication" for a particular drug, the developer can renew its patent and keep generic competitors off the market for another three years. For most industries, this would have a pretty modest impact on revenue. But in the business of curing ills, in which price tags can be very high and demand is often buoyed by nature, those three years can make a huge difference.

Thirteen clinical trials met inclusion criteria. These clinical trials were designed to investigate 10 patented drugs and one investigational new drug. Nine of these trials were testing ‘blockbuster’ drugs with patents that had expired or would expire in the next 2 years. Table 1 [see full text] provides a summary of trial drugs, their patent status, and their 2012 revenue [obtained from the drug manufacturers’ 2012 annual reports]. The trial drug manufacturer was one of the sponsors or collaborators for 8 of the 13 trials [62%].

… Take, for example, the drug Cymbalta – one of a group of drugs referred to by the industry as "blockbusters" – drugs that rake in at least $1 billion in annual revenue. Cymbalta, which is prescribed for major depressive disorder and generalized anxiety disorder, earned its blockbuster title almost five times over in 2012, bringing in nearly $5 billion to developer Eli Lilly. Lilly’s patent on Cymbalta expired in December 2013, and the developer should soon begin to lose revenue to generics… But thanks to the changes made by the APA to the DSM, the money will likely keep rolling in.

… In past editions of the DSM, a so-called bereavement exclusion from major depressive disorder recommended that actively grieving individuals not be diagnosed with depression. In the DSM-5, this recommendation has been erased, giving rise to "bereavement-related depression" – a subset of major depressive disorder that is treatable by all the standard methods [and drugs] that ease depression. But if you didn’t need to treat the loss of a loved one with medication in 2000, is it really necessary in 2014?

… Companies like Lilly certainly want it to be – and they may just get their way. Public records regarding clinical investigations show that Lilly’s expired patent on Cymbalta will in all likelihood be renewed, as it is currently the focus of a new trial for the pharmacological treatment of bereavement-related depression. In other words, it’s going to end up being the drug of choice for treating what was merely called "grief" at the time of Lilly’s original patent filing.

… The APA’s disclosures regarding the DSM-5 include several instances that appear to support the contention that the public’s best interest has fallen in the shadow of financial gains. Take, for example, the Cymbalta trial: Of the 43 APA panel members involved in the implementation of this new diagnosis, 20 had disclosed financial conflicts of interest with drug manufacturer Lilly. These disclosures, which range from stock holdings and consultancies to honoraria and research funding, suggest that more diagnoses ultimately means more money for everyone involved…

hat tip to Altostrata…

Was there a direct connection between the influence exerted by the pharmaceutical companies and their affiliated psychiatrists in high places that opened up this possibility of patent extensions? Given the track record of the industry/academic psychiatry alliance for decades, only a fool would say "No." And whether that could be proved in court doesn’t even matter. That’s the kind of thing David Kupfer, Derral Regier, James Scully, and the APA Presidents/Trustees are there to protect us from having to even think about. Instead of handing out defensive homilies and damage control press releases, we could’ve used a lot more evidence that they were doing their jobs. And this is also why even the appearance of Conflict of Interest has been the traditional standard in medical ethics until the recent era.

Frances believes that while pharmaceutical companies may indeed pounce at every opportunity to drive revenue and retain exclusivity, the panel members themselves have also been blinded by their desire to help "the missed patient" – the individual in pain who, for one reason or another, disappears through cracks in the system. "The experts on the DSM-5 were given a tremendous amount of freedom, and what this resulted in was a kind of dream list of new diagnoses that turned the everyday problems of life into mental disorders," he tells Newsweek. "They are naive about how something that may work in their hands will be misused in the average practice." adding "The biggest risk is not financial conflict of interest, but intellectual conflict of interest," he says. "The pressure of experts is always to expand their area."

Finally, as a policy objective, it is critical that the APA recognize that transparency alone is an insufficient response for mitigating implicit bias in diagnostic and treatment decision-making. Specifically, and in keeping with the Institute of Medicine’s most recent standards, we recommend that DSM panel members be free of FCOI. In the future, DSM panel members should also be prohibited from serving as PIs of trials for any disorder being considered for inclusion in the DSM.