I thought I read the final chapter in the tale of Pfizer’s shady marketing practices for Neurontin years ago. Sadly, there’s at least one more chapter to go.

Recall that in in 2008, leaked documents from a US District Court revealed that Pfizer had covered-up the results of a clinical trial which showed the drug didn’t work for chronic nerve pain, even as it promoted off-label use of the anti-seizure drug for that purpose. The next year, it was revealed that Parke-Davis (now a subsidiary of Pfizer) took advantage of lax disclosure policies by certain medical journals to publish 13 articles promoting off-label use of Neurontin that were ghostwritten and funded by the company without disclosing such arrangements.

Now, it has come to light that Parke Davis’ marketing department sponsored a Seeding Trial of Neurontin back in the day—that is, a trial portrayed deceptively as a patient study but whose real aim was to encourage prescribers to use the drug.

The trial was STEPS, the ‘Study of Neurontin: Titrate to Effect, Profile of Safety’ trial. More than 772 physician ‘investigators’ and 2800 patients participated in STEPS.

The stated objective of STEPS was to study the safety, efficacy and tolerability of Neurontin. However, after reviewing documents compiled for a pair of lawsuits against Pfizer and its subsidiaries, Joseph Ross and colleagues concluded that the actual objective was to increase prescribing rates by ‘investigators’ in the study. Neither the ‘investigators’ nor their patients were informed about the real purpose of STEPS.

The trial worked, from Parke-Davis’ point of view. Physician ‘investigators’ prescribed 38% more Neurontin as a result of their participation in the trial.

The drug company also leveraged the patient recruitment process to market Neurontin to ‘investigators,’ Ross’ group found. Company representatives asked ‘investigators’ to set-aside certain days on their schedule in which epilepsy patients comprised the bulk of the appointments, thereby permitting the reps to be present and promote Neurontin at the moment of truth. The reps even helped collect patient data for the trial.

The smoking gun though, was uncovered in the company’s marketing plans, which cited the trial itself, not its anticipated results, as central to the promotion of Neurontin. For example, a 1995 report listed STEPS as a deliverable under the strategy “Solidify Neurontin’s position with neurologists and select primary care physicians as the safe and easy add-on for refractory patients.” Another document stated that “the rapid growth of Neurontin depends on the ability to influence the large population of community neurologists that see the majority of nonrefractory seizure patients. The STEPS trial…was a strong start to this…”

To be clear, Parke-Davis’ marketing department, not its clinical research department designed and conducted STEPS.

What’s Wrong with Seeding Trials?
Seeding trials are not illegal, but they are profoundly unethical. They don’t permit patients to make informed decisions about participating, since the real (marketing) objectives are not disclosed. Ross’ group reports that 11 patients died and 73 more experienced serious adverse events during STEPS, so they were exposed to considerable risk. Physician ‘investigators’ were also not informed that they, in fact, were the real study subjects in STEPS. Indeed, the very success of STEPS relied on deception; few physicians or patients would participate in studies with primary marketing objectives and little scientific value.

Remarkably, no one knows how many seeding trials have been carried out over the years, since their results are often not published (after all, the goal is to impact prescribing, not to contribute to medical knowledge). Other than Ross’ account of STEPS, the only other seeding trial to have been exposed in detail was Merck’s ADVANTAGE trial, which was designed to increase prescribing for Vioxx, a drug that was later pulled from the market after being linked to cardiovascular disease. As was the case in STEPS, a review of documents obtained during litigation was required to expose the problem.

What Can Be Done?
The FDA is largely powerless to prevent seeding trials. It only oversees trials designed to support new drug applications or to support label or advertising change requests. That leaves things up to the institutional review boards at individual institutions, which is not comforting since only one IRB (at Johns Hopkins) spotted problems with STEPS and failed to approve it.

It may finally be time to ramp-up government oversight of IRBs, therefore. Why not require all IRBs to register and become accredited, for example? Why not penalize institutions whose IRBs approve trials that are unethical, as was the case in STEPS? Why not proscribe commercial (as opposed to institutional) IRBs altogether, since they have intolerable conflicts of interest? Why not require that all research protocols be posted in a publicly available repository? At a minimum, this would make it easier to identify seeding trials—at least retrospectively. We wouldn’t have to wait for a lawsuit.

Even if all these recommendations were implemented however, clinical investigators and physicians themselves must ultimately step-up and accept their roles as ‘the last line of defense’ (as I mentioned here). It comes down to asking yourself this question: does the post-marketing study in which you have been invited to participate seem to have marketing objectives or actual science in mind?

African-American Men More Likely to Stay Alive In Prison than Out. A study of North Carolina inmates found that African-American males are half as likely to die in prison as out of prison. The study, in the Annals of Epidemiology, found that African-American inmates were protected against drug and alcohol-related deaths, fatal accidents and some chronic diseases.

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FDA Issues Draft Document on Mobile App Regulations. The 30-page draft provides guidance outlining how mobile medical apps should be regulated as medical devices, targeting an issue that has long plagued physicians looking to adopt apps and vendors wondering how far they can go without incurring the regulations.

Reddit Cofounder Charged With Hacking MIT Computer. Federal prosecutors have accused Aaron Swartz of stealing 4 million documents over a 3-month period in 2010. He faces charges of wire fraud, computer fraud, unlawfully acquiring information and recklessly damaging a protected computer. If found guilty, Swartz could spend 35 years in jail and be fined $1 million.

Patients Pick Hospitals for their Social Media Presence. In a survey, 57% of consumers said that a hospital’s social media connections would strongly affect their decision to receive treatment at that facility, according YouGov Healthcare. 81% consider a hospital with an active online presence to be more “cutting edge.”

eRx Systems May Not Reduce Medication Errors. Outpatient electronic prescribing systems don’t cut out the common mistakes made in manual systems, according to a study in the Journal of the American Medical Informatics Association.

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Mass. General Disciplines Three Psychiatrists. The Harvard-affiliated teaching hospital disclosed sanctions against Joseph Biederman, Thomas Spencer and Timothy Wilens for violating hospital ethics guidelines by failing to adequately report seven-figure payments they received from drug companies.

Facebook To Unveil Skype-Powered Video Chat Next Week. The social networking behemoth reportedly will unveil a Skype-powered video chat platform later this week.  The move may be a response to Google+, the search giant’s answer to Facebook, which already has a group video chat feature.

Social Media Shows Promise for Clinical Trials. Social media can be used to increase enrollment and reduce clinical trial delays, according to a new survey by Blue Chip Patient Recruitment.

ACSM Releases New Exercise Guidelines. The new guidelines by the American College of Sports Medicine aren’t all that different from their old ones, except they emphasize that sitting for long periods is a health risk that can’t be negated simply by exercising regularly.

Spine Journal Takes Aim at Infuse Research. The Spine Journal is devoting an entire issue to critical reviews of published studies of Medtronic’s bone morphogenetic protein-2 product known as Infuse (see Pizaazz coverage of the matter here).

Google+ Begins Limited Field Testing. The company’s top secret social layer supposedly turns the search engine into a giant social network. It’s the culmination of a year-long project, and amounts to Google’s answer to Facebook.

Social Media Being Used as a Platform to Disclose Illness. The Internet has not only transformed how consumers gain access to health information, it is also significantly changing how they seek comfort during a health crisis, according to new research from Russell Herder. 

Spinal fusions jumped 1,500% among Medicare patients between 2002 and 2007. The explosion had nothing to do with changes in prevalence of the conditions for which the complex surgery is performed. It had everything to do with the release of Infuse, a bone growth stimulator that reduces the complexity of the procedure.

Infuse (pictured) is marketed by Medtronic. It was approved by the FDA in 2002, specifically for spinal fusions of the lumbar (lower) spine using a particular surgical technique: the frontal approach. Soon after the FDA green-light however, surgeons began using it for other kinds of lumbar fusions and cervical (neck) fusions as well. Peer-reviewed studies of these non-approved uses helped drive the explosion in spinal fusions. Now, remarkably, off-label use accounts for 85% of Infuse use. The biological garners nearly $900 million in annual revenues for Medtronic.

There’s More to the Story
Unfortunately, newer studies of spinal fusion have found it to be no more effective for common back pain than physical therapy. Use rates of Infuse have not responded to this growing literature.

Beyond this, the off-label use studies mentioned above were sponsored by Medtronic and led by scientists that received tens of millions of dollars’ worth of royalty payments and consulting fees from Medtronic. It has recently been alleged that these scientists knew about certain complications caused by Infuse, and either failed to disclose them or de-emphasized them in their write-ups.

The complications include some that are potentially fatal– neck swelling severe enough to compromise breathing, and possibly an increased cancer risk, for example. They also include sterility in men, a complication Medtronic and surgeons with financial ties to Medtronic appear to have been aware of—but did not report–since 2002.

These alleged shady behaviors came to light just recently, when researchers re-examined data from the Medtronic sponsored trials. The data was submitted to the FDA, but never made it into the literature that spawned widespread, off-label use of Infuse.

The matter has now escalated all the way to the Senate Finance Committee. In a letter to Medtronic last week, Committee members Max Baucus and Charles Grassley claimed that “doctors conducting clinical trials examining the safety and effectiveness of Infuse on behalf of Medtronic (knew that Infuse could) cause medical complications, but failed to report this in the medical literature.” The senators asked Medtronic to send them all documents and communications relevant to these studies, as well as a detailed account of payments made by Medtronic to all surgeons involved in the studies.

The run-in with Senate Finance is just the latest in a series the company has had with federal officials. In 2008, the Justice Department opened an investigation to determine whether the company illegally promoted off-label uses of Infuse. A year later, an Army investigation found that a former Army surgeon, paid by Medtronic, had falsified the results of a study involving Infuse. That’s not counting recently unsealed testimony given in a 2002 lawsuit filed by a former Medtronic lawyer which alleged that the company illegally gave surgeons incentives to use its products.

What Do We Make of This?
Senators Baucus and Grassley have turned harpooning the business practices of companies that profit from health care into an art form. They’re particularly adept at selecting issues that garner popular support. In this case, they argue that patients and physicians have a right to expect that the information on which they rely is accurate, unbiased and comprehensive. Applying that thesis to the Medtronic situation, the point is that when studies of drugs or devices are published by scientists with financial ties to the company that markets the product in question, this needs to be disclosed, even if the payments aren’t linked to the product being evaluated. We couldn’t agree more.

Then again, Senate Finance isn’t equipped to take-on more than a few of the many egregious spectacles in which health companies have recently become enmeshed. More potent lines of defense include the editors of peer reviewed journals, who need to re-evaluate their disclosure policies. They also include physicians, who must step to the plate more often in a watchdog role, alerting others in the profession about potentially unsavory behavior or previously unreported complications associated with drugs and devices. Finally, as Maggie Mahar points out, the mainstream media also plays a role by continuing to pursue the story of money-driven medicine.

“The repetition is crucial,” she said. “Education depends on repeating the same message, and making it clearer over time.”

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North Carolina Mulls Amends for Sterilizations. A consensus is emerging on how to compensate men and women sterilized as part of one of the nation’s largest eugenics programs. But the state’s fiscal problems mean it’s unlikely the aging victims will get paid anytime soon.

HIV Cases Fall by 25% between 2001-1009. The data comes from a press release by the Joint United Nations Programme on HIV/AIDS. Researchers attribute the drop to safer sex behaviors in men and women, in part because of increased awareness and prevention campaigns.

Twitter Limited as a Tornado Warning Tool. Twitter has limitations as a means for notifying the public about imminent tornado danger, says Crisis Commons, an organization dedicated to developing innovations in crisis management through open data and volunteer technology communities.

Bomb Blast Damage Found in Brain Scans of GIs. Neuron damage in explosion-related “mild” traumatic brain injuries can be more extensive than previously thought and is not necessarily related to the severity of clinical symptoms, researchers said.

CBO Says Advertising Moratorium on New Drugs Will Have Little Effect. The Congressional Budget Office examined the consequences of proposals to place a moratorium on consumer advertising of newly approved drugs during their first two years and concluded such a measure would have little effect.

Rule Would Give Patients Access to Privacy-Related Data. Under HIPAA law, providers, health plans and other healthcare organizations must track electronic access to protected health information, but they are not required to share this information with patients. A rule proposed by CMS would require providers to inform patients that they can request this information.

Retraction Sought, Refused on XMRV-CFS Study. Authors of the original paper linking a mouse retrovirus to chronic fatigue syndrome have refused a request from the journal’s editor to retract it, in the face of growing evidence suggesting their findings were caused by lab contamination.

Cellphone Use Possibly Carcinogenic. Cellphones are “possibly carcinogenic to humans,” according to experts working on behalf of the World Health Organization. 

BCBS of Florida Releases App for iPhone, Android. Known as Florida Blue, the mobile app provides general health information, health management tools and benefit information for members.

Egyptian General Admits ‘Virginity Checks’ Conducted on Protesters. A senior Egyptian general admits that “virginity checks” were performed on women that were arrested at a demonstration this spring, the first such admission after previous denials by military authorities

Proposed Bill Would To Expand Telehealth Services for Service Members. The “Telemedicine and E-Health Portability Act” has bipartisan support. It is designed primarily for mental health services but it can be extended to other services as well.

Privacy Issues Raised as Prisons Roll-Out EHRs. As prisons take steps to implement electronic health records, debate is stirring over whether mining inmates’ medical data would violate their privacy.

‘DC to VC’ Summit Seeks To Fund New Health IT Ideas. Morgenthaler Ventures has announced a nationwide contest to find the best startup ideas in health IT. The competition is open to entrepreneurs seeking seed or Series A funding.

Lower Risk of Death Linked to Optimism in Heart Patients. If newly diagnosed heart disease patients who must undergo treatment are optimistic and expect they’ll resume normal activities, they do better according to Duke researchers.

Artsy, Museum-Going Men Are Happier. Men who enjoy taking in the ballet or browsing art museums are more likely to be happy with their lives and satisfied with their health than men who don’t, a study has found.

Transgender Detainees Cut-Off from Hormone Drugs. An advocacy group is claiming that jail is depriving immigration detainees of  ’adequate health care’. The group, supported by the AMA and others, says that hormone replacement therapy is indicated for cases of gender identity disorder.

Vermont Senate Approves Single-Payer Health Care. The state is on track to become the first one in the nation to offer a single-payer system and universal health coverage.

Wolters Kluwer in Deal to Acquire Lexi-Comp. Drug information provider Lexi-Comp is the latest of several WK acquisitions that have focused on providing decision support at the point-of-care. 
 
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Guantanamo Docs Neglected, Concealed Medical Evidence of Torture. The evidence includes bone fractures, lacerations, and symptoms of post- traumatic stress disorder, according to Physicians for Human Rights.

Convicted Rapist Next in Line for a Heart Transplant. New York taxpayers would pick up the $800,000 tab.

New Health Wonk Review is Posted! ‘Spring Has Sprung and Mud Still Flung’ edition, created by the folks over at The Incidental Economist. Features @Pizaazz post on Alzheimer’s guidelines.