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 – 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 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…” (more…)

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. (more…)

Today, consumers can purchase dozens of medical tests without a prescription–tests that tell them whether they are pregnant, have a urinary infection, their cholesterol is too high, and so on.

Should direct-to-consumer (DTC) genetic tests be as readily available? These are the mail-in saliva tests that tell consumers about their genetic susceptibility to Alzheimer’s disease, type 2 diabetes, heart disease and other conditions.

DTC genetic tests are different from the genetic tests that have been used for decades in prenatal and newborn screening, and more recently in predictive testing (like the BRCA test for breast cancer risk).

The difference is not the substrate being tested. In both cases, it’s DNA. Rather, it’s who owns the testing process.

For the legacy DNA tests, health professionals own the process. As per protocol, they obtain permission (informed consent) from patients before ordering the test. Then, they consult with and support the patient once the results are known.

In contrast, DTC genetic tests transfer ownership of the genetic testing process to consumers. A person can decide for herself whether to get a DTC genetic test. She doesn’t need permission from a provider, and has no obligation to share the information with her provider.

This bothers many physicians, bioethicists and consumer advocates. They point out that DTC genetic test reports can be difficult to interpret (for physicians as well, I might add, despite claims that they are universally qualified to do so). They decry the lack of regulatory oversight of testing facilities which might help assure the accuracy and reliability of the information. Furthermore, reports of “egregious…deceptive marketing” by some DTC genetic testing vendors suggest that consumers maybe harmed, they say.

These people call for regulatory oversight of DTC genetic testing. The FDA has in certain limited instances, already begun to do just that.

Physician organizations tend to support the regulation of DTC genetic testing. In particular, they favor rules that transfer ownership of DTC genetic testing to (guess who?) physicians who can then serve as custodians of the information, just as they do for the traditional genetic tests mentioned above.

Set the Data Free
I disagree. People who want access to their genetic-risk information should be free to pay their own money to obtain it, period. The only place where regulation has a role in DTC genetic testing is to assure the quality of the results being generated. That’s it.

(more…)

For the first time in 30 years, an expert panel has updated guidelines for the diagnosis of Alzheimer’s disease. The long overdue facelift should favorably impact care for millions and accelerate badly needed research on the disease.

The guidelines were produced by representatives from the National Institute on Aging and the Alzheimer’s Association. They portray Alzheimer’s for the first time as a three-stage disease. In addition to ‘Stage 3,’—the full-blown clinical syndrome that had been described in earlier versions of the guidelines—the new guidelines describe an earlier ‘Stage 2,’ of mild cognitive impairment due to Alzheimer’s, and a ‘Stage 1, or preclinical’ phase of the disease. The latter can only be detected with biochemical marker tests and brain scans.

The guidelines legitimize years’ worth of observations by the family members of Alzheimer’s patients, who recognize in retrospect that Grandpa had a slowly progressive cognitive disorder long before he was diagnosed. The guidelines also reflect progress on the research front, where it has now been established that the disease begins years before patients become symptomatic.

Alzheimer’s patients and their families, and the teetering US health system that supports them, would have been better served by the publication of these guidelines 2-3 years ago.

The science was compelling enough back then, and a 2 to 3 year lead-time on research could have had an enormously positive impact on our economy and our health system. In a report last summer for example, the Alzheimer’s Association concluded that unless disease-modifying treatments are found quickly, the number of Americans with Alzheimer’s disease will jump from 5.1 million to 13.5 million by 2050. The total costs of caring for these folks will have exceeded $20 trillion, in today’s dollars, by then. A lions’ share of these expenses will be borne by government entitlement programs, Medicare and Medicaid.

The New Guidelines Will Improve Care
Meanwhile, several commentators have criticized the new guidelines as confusing and stress-provoking. ‘Why should we rush to tell people they have something we can’t treat?’ is the crux of their argument.

These people have it wrong. Denial is not the way to go with Alzheimer’s. The sooner patients and their families find out they have it or are at risk to develop it, the more time they have to develop care plans that reflect their preferences. Mildly affected individuals get to decide for themselves how to enjoy what may be a limited number of years-worth of relatively unimpaired mental functioning. They also get to decide whether to participate in clinical trials and which ones to participate in. They and their families can access counseling and support groups more quickly, a benefit that can improve the quality of life for everyone involved. Even providers themselves can use the enhanced lead-time to implement a patient support plan that respects the needs of the patient and his family.

Today, full-blown Alzheimer’s affects 5.1 million Americans. In all likelihood, at least that many have mild cognitive impairment due to Alzheimer’s (the new ‘Stage 2′). These are the people that will benefit immediately by the expanded definition.

The New Guidelines Will Improve Research
By formally recognizing that Alzheimer’s is slowly progressive and establishing criteria for each stage of the disease, the guidelines facilitate scientific inquiry into various diagnostic and therapeutic options. They allow patients to be grouped by stage of illness (a breakthrough similar to what tumor staging has done for cancer research). Most importantly, they encourage patients to enter clinical trials at a time in the natural history of their disease when treatment success is more likely. (more…)

Younger, healthier patients would be more likely than older, sicker ones to get the best kidneys if a new proposal by UNOS, the US’ organ transplant network is accepted. The proposal would supersede an existing first-come, first-served policy. It is designed to match-up the life expectancies of patients with the expected functional life of donated organs.

According to the proposal by the United Network for Organ Sharing, recipients and donor organs will be graded. The top 20% of patients and kidneys—based on age and health—will be placed in separate pools such that patients with the longest life expectancies will receive the best kidneys. The other 80% will be assigned to a separate a pool from which UNOS will match recipients and donors such that the age difference between the two is no greater than 15 years. For example, a 60 year-old person could only receive a kidney from donors who are between the ages of 45 and 75.

“Right now, if you’re 77 years old and you’re offered an 18-year-old’s kidney, you get it,” Richard Formica, a member of the UNOS  panel that penned the new proposal said in an interview. “You’ll die with that kidney still functioning…a 30-year-old could have gotten that kidney and lived with it to see his kids graduate college.”

The new proposal would affect the 90,000 or so people that are currently on waiting lists for donor kidneys. In 2009, 10,442 kidney transplants were performed using organs from deceased individuals. An additional 6,387 procedures involved live donors who typically specify the recipient. Nearly 5,000 people die while waiting for a kidney transplant.

Many transplant surgeons and medical ethicists support the proposal. Arthur Caplan, a leading bioethicist at the University of Pennsylvania reflected this sentiment as follows: “If it’s a choice between saving grandpa or granddaughter, I think you save granddaughter first.” (more…)

Although Facebook has long-since been woven into the fabric of modern life, it continues to pose ethical challenges for government officials and professionals in many fields. How much personal information should they share with others? Are their traditional codes of conduct robust enough to cover the behaviors associated with the use of Facebook and other social media outlets?

Physicians, nurses and other health professionals know they must never disclose confidential health information concerning their patients on Facebook or anywhere else. Beyond this, new media outlets create countless situations in which “acceptable” behavior for government officials and professionals remains unclear.

To their credit, some professional societies including the AMA have recently issued guidelines for acceptable behavior on social media outlets. Surprisingly however, scientists have published few studies describing professionals’ actual use of such sites.

Recognizing this gap, Ghassan Moubarak and colleagues at Hopital Lariboisiere in Paris designed a questionnaire to study the way young physicians use Facebook. Moubarak’s group mailed the survey to 405 residents and fellows at Rouen University Hospital. Nearly half of them responded, including 160 residents and 42 fellows. The mean age of respondents was 29.

Seventy-three percent of the survey respondents reported having a Facebook profile. Nearly a quarter of them, 24%, said they visited the site several times per day, and an additional 28% reported visiting it once per day.

Ninety-nine of the respondents who had a Facebook profile used their real name on it. Over 90% of the respondents also displayed their birthdates and a headshot, although only 59% listed their current university and 55% listed their current position. Sixty-one percent of the respondents had modified privacy settings on the site, and 85% said they would never accept friend requests from patients. The remaining 15% said they would decide about friend requests from patients “on an individual basis.” None of the respondents said they would automatically accept a friend request from a patient. (more…)

US scientists are more likely than their counterparts in other countries to publish research studies containing fabricated or falsified data, according to a study by R. Grant Steen. And scientists who perpetrate fraudulent research like this are more likely than most to repeat the egregious behavior.

To reach these conclusions, Steen reviewed all 788 English language research papers that had been retracted from the PubMed database during the past decade. Compiling relevant information from the associated retraction notices, Steen classified the causes for retraction as being due to either fraud or an honest procedural mistake.

Steen found that about 75% of the retractions resulted from procedural error, and 25% were caused by fraud. Remarkably, papers retracted because of fraud were published in journals with a higher “impact factor,” that is, journals containing articles that are cited more frequently by other scientists.

Steen also found that articles retracted because of fraud tended to have more co-authors and to take longer to retract than the ones retracted because of procedural mistakes.

Of the 788 retracted papers, fully one-third featured a US-based scientist as the first author, and one-third of these were retracted because of fraud. Asian nations accounted for an additional 30% of the retracted papers, although only one-fourth of them were retracted because of fraud. In fact, the US was the only country in which significantly more papers were retracted because of fraud than procedural errors.

A stunning 53% of all fraudulent papers had been penned by a “repeat offender,” a first author that had been associated with a retracted paper in the past. In contrast, only 18% of the papers retracted because of mistakes featured first authors that had been previously involved with a retracted paper.

“The duplicity of some authors is cause for concern,” Steen wrote. The results of this study, “suggest that papers retracted because of data fabrication or falsification represent a calculated effort to deceive. It is inferred that such behavior is neither naïve, feckless nor inadvertent.”

Unsealed documents from a dispute involving Wyeth Pharmaceuticals show the drug company paid ghostwriters to prepare articles that emphasized positive findings about post-menopausal hormone replacement therapy as part of a strategy to stem growing public concern about the treatment.

The articles include several dozen clinical trial reports and literature reviews. They were reviewed by Adriane Fugh-Berman, an associate professor in the Physiology Department at Georgetown.

Fugh-Berman published her review in PLoS Medicine. She presented her findings while serving as a paid expert witness in a court case brought by 14,000 plaintiffs. These people allege that their breast cancer might have been caused by a Wyeth-made hormone replacement drug known as Prempro.

In her testimony, Fugh-Berman said the ghostwriting strategy included promoting off-label, unproven uses of Prempro such as the prevention of dementia, vision problems, wrinkles and Parkinson’s disease. The strategy also featured a hearty defense of supposed cardiovascular “benefits” of hormone replacement therapy and an attempt to cast doubt about several competing therapies.

The ghostwritten articles were circulated to drug representatives and eventually to physicians.

The ghostwriting outfit at the center of the matter is DesignWrite, medical education and communication company. Wyeth or its representatives apparently paid DesignWrite $25,000 per ghostwritten report of a clinical trial. DesignWrite also wrote 20 review articles, receiving $20,000 a pop.

“The medical profession must ensure that prescribers renounce participation in ghostwriting, and ensure that unscrupulous relationships between industry and academia are avoided rather than courted,” the PLoS study says.

In a statement to Reuters, Pfizer (which now owns Wyeth) tried to dismiss the report. “Even with her critical perspective, (Fugh-Berman) could not establish that there were inaccuracies in any of the peer-reviewed articles, or that their authors relinquished control over their work,” the statement said.

The Affordable Care Act has catapulted the US Preventive Services Task Force from an obscure agency which produced unenforceable guidelines about screening and preventive services into one whose recommendations directly impact reimbursement.

The health reform law requires insurers to pay in full for services receiving an A or B recommendation from the Task Force. The flip-side is that insurers may not have to pay at all for services that are not recommended by the Task Force. As a result, the Task Force’ new best friends include lobbyists and disease advocates who want their priorities – things like screening for Alzheimer’s disease, HIV and diabetes or HIV – to get covered.

The American Diabetes Association, for example, is advocating that insurers be required to cover a broader population than current Task Force recommendations suggest. Current recommendations are that only patients with high blood pressure should be screened.

The HIV Medicine Association has made a similar argument to the Task Force. It claims that a key reason why 20% of people infected with HIV are unaware of that fact is because most insurers don’t cover the costs of testing.

“If you want to be evidence-based, lobbying doesn’t fit,” Ned Calonge, the chairman of the Task Force told the Washington Post. “My charge to members would be to stay true to the methods and the evidence.”

The Task Force, by the way, is the same one that caused a stir before the 2008 presidential election when it recommended that women should start receiving screening mammograms at the age of 50, rather than 40. That move was eventually trumped by an amendment to the Affordable Care Act which required insurers to cover mammograms for women in their 40s.

A Presidential commission tasked to explore ethical issues associated with man-made life has held initial meetings to better understand the matter and begin figuring out whether additional regulations are needed for the burgeoning new field.

In May, J. Craig Venter and colleagues reported creating a self-replicating synthetic bacterial cell, a landmark achievement that many believe represents the dawn of an era in which man can create brand-new organisms that produce drugs and fuels, and perhaps gobble up oil spills on the cheap.

The report prompted President Obama to organize the commission. He has asked it to produce recommendations within 6 months.

Venter attended the opening meetings himself. He suggested that researchers in the field could, perhaps, produce seed stock for a flu vaccine in just 12 hours. “With rapid DNA sequencing, we can predict, we think, well in advance what the changes will be for next year’s flu before the WHO even makes the decision as to the vaccine stocks,” he told  BurrillReport.

Venter added that synthetic biologists could also potentially cause harm—as by producing new, highly lethal viruses. Venter insisted however that such behavior could “be readily prevented by some straightforward regulations.”

Kristala Prather, a Chemical Engineering professor at MIT concurred that, that although the potential benefits are large, so too are the risks. “Because there is this information gap between what we understand about biology and what our capabilities are, it is impossible to predict what’s going to happen in every experiment,” she told GenomeWeb News.

The commission will hold more meetings in September and November.