Life Science Compliance Update

March 23, 2016

Senate HELP Committee Continues Work on 21st Century Cures Corollary

Earlier this week, the Senate Health, Education, Labor, and Pensions (HELP) Committee held a hearing on a package of legislative measures that are targeted at facilitating medical innovation. This hearing, the second in a set of three, is the Senate's response to the House-passed 21st Century Cures Act (H.R. 6). We wrote about the first hearing, and a recap can be found here.

While the second meeting featured much partisan debate and fanfare, the Committee advanced all seven medical innovation measures before them, with six passing by voice and one measure passing by roll call vote of 20-2.

In opening statements, Senator Lamar Alexander, Committee Chairman, acknowledged the anticipated contention on the panel over what he referred to as a "surge" of additional mandatory funding requested by Democrats for the Food and Drug Administration (FDA) and the National Institutes of Health (NIH). Even expecting contention, the Chairman expressed optimism about the Committee's capacity for compromise, stating that if the Committee successfully creates an innovation agenda, it may be the "most important legislation passed this year."

As may be expected, Ranking Member Senator Patty Murray and Senator Elizabeth Warren both showed strong support for increasing mandatory funding for the FDA and the NIH, each introducing an amendment to S. 1878: one to create a medical device evaluation system and the other to create a biomedical innovation fund. Senator Murray also expressed concern that some of these bills may increase FDA responsibilities and not compensate the FDA for that. While both senators started out firmly believing that any agreement needed to include increased funding, they both withdrew their amendments, including any requests for additional funding, in order to find other consensus points and come to an agreement.

The measures approved in the Committee are as follows:

The Advancing Hope Act of 2015

This bill amends the Federal Food, Drug, and Cosmetic Act (FDCA) to expand the priority review voucher program for rare pediatric diseases to including treatments for both sickle cell disease and pediatric cancers. The voucher program will be extended by removing the provision that terminates the program one year after the FDA's issuance of three rare pediatric disease vouchers. However, a voucher may not be issued for a rare pediatric disease product, if a voucher was ever issued for the product as a tropical disease product. Additionally, a drug sponsor that intends to request a voucher for a rare pediatric disease drug must notify the FDA of their intent to do so upon submission of their new drug application.

The bill's sponsor, Senator Robert Casey explained that this program is integral to fostering innovation and incentivizing private companies to invest in rare children's diseases. Such an incentive is necessary because private companies tend to not see a return on research investment in this area.

This is the one measure passed via a roll call, following adoption of the following amendments: (1) specify the criteria for "rare pediatric disease," (2) insert a section related to rare pediatric disease product applications, (3) require the comptroller to conduct a study on the GAO report on the effectiveness of awarding priority review vouchers for the sponsorship of rare pediatric disease product application, and (4) require the results of the study to be reported to congress.

The Advancing Breakthrough Medical Devices for Patients Act of 2015

This bill amends the FDCA to expand the FDA's priority review of breakthrough medical devise to include all classes of devices. Currently, only new or highest risk (Class III) devices are eligible. However, this bill would make it so that upon a sponsor's request, the FDA would be forced to determine whether a device meets the criteria for priority review as a breakthrough device.

To expedite the development and review of designated medical devices, the FDA must: "assign a team of staff for each device, adopt an efficient process for dispute resolution, provide for interactive and timely communication with the device sponsor, expedite review of manufacturing and quality systems compliance, disclose to the sponsor in advance the topics of any consultation between the FDA and external experts or an advisory committee and provide the sponsor the opportunity to recommend external experts, [and] assign staff to address questions by institutional review committees concerning investigational use of the device."

Senator Richard Burr emphasized the idea that this measure would not change the standards that devices are required to meet in order to reach the market, but instead simply changes the approach by which device approvals can be accelerated.

The Medical Countermeasures Innovation Act of 2015

This bill encourages the development of medical countermeasures in case of biological attacks and naturally occurring outbreaks. This bill is intended to build upon the Pandemic and All-Hazards Preparedness Act, by leveraging the innovation of the private sector through priority review vouchers. The urgency of this problem has been exemplified with the Ebola and Zika outbreaks over the past year.

The Medical Electronic Data Technology Enhancement for Consumers Health Act

This bill amends the FCPA to exclude several classes of devices from FDA-regulation as a medical device. Some of the included classes are: administrative, operational, or financial records software used in health care settings; software for maintaining or encouraging a healthy lifestyle unrelated to medical treatment; electronic patient records, excluding software for interpreting or analyzing medical image data; software for clinical laboratory testing, excluding software for interpreting or analyzing test data; and software that provides medical recommendations and the basis for those recommendations to health care professionals, excluding software for acquiring, processing, or analyzing medical images or signals.

The bill also states that the FDA must classify a medical device accessory according to its intended function, not the classification of the medical device with which it is used.

This measure was adopted without any discussion.

The Combination Product Regulatory Fairness Act of 2015

This bill attempts to address regulations on combination drug and device products. There was little discussion accompanying this bill, but Senator Casey did briefly speak out in favor of the measure, noting that it will allow for improved communication with the FDA and manufacturers.

The Patient-Focused Impact Assessment Act of 2015

This bill amends the FDCA to require the package of information published by the FDA upon approval of a new drug to include documentation of efforts to assess patient engagement. The required documentation must include identification of patient-focused drug development tools and an explanation of whether certain information was reviewed or examined, including any patient preferences and patient-reported or caregiver-reported outcomes. The FDA is also required to annually summarize, and publish, the data that is collected in this documentation.

Senator Susan Collins, a cosponsor of the bill, believes that patient input is a valuable resource and should play a larger role in FDA decision-making.

The Adding Zika Virus to the FDA Priority Review Voucher Program Act

This bill also amends the FDCA, to add the Zika virus to the list of tropical diseases under the priority review voucher program. The priority review voucher program awards a voucher to the sponsor of a new drug or a new biological product that is approved to prevent or treat a tropical disease, which allows the holder of the voucher to have a future new drug or biological product application acted upon by the FDA within six months.

Chairman Alexander mentioned at the outset of this meeting that the Zika virus is a top concern and priority for the HELP panel.

The final HELP Committee on medical innovation is slated for April 6, 2016, at which time Chairman Alexander hopes to have a final package ready for floor consideration.

May 19, 2015

"Reconnecting the Dots — Reinterpreting Industry–Physician Relations" Provides A Balanced Look At Physician-Industry Collaboration and Conflicts of Interest


Lisa Rosenbaum, MD recently published an article entitled “Reconnecting the Dots—Reinterpreting Industry-Physician Relations,” in The New England Journal of Medicine. Rosenbaum’s article provides a refreshingly balanced analysis of financial conflicts of interest in medicine. “Although most observers agree that we must mitigate the risk of bias introduced by these relationships, the benefits wrought by interactions between physician-scientists and industry at the basic or translational research level are equally clear,” she states. “The question, then, is how to best manage conflicts of interest while preserving the collaborations on which medical advances depend.”

Collaborations and Conflicts of Interest

“Physician-industry interactions have been critical to the development of a large percentage of the medical products that allow physicians to prevent heart attacks, cure cancers, and restore mobility to the elderly,” Thomas Stossel, M.D., a distinguished Harvard hematologist and research recently noted. “Despite such progress and the role of physician-industry interactions in fomenting it, physicians are reducing or severing their relationships with biopharmaceutical and medical device companies out of fear that their patients will mistakenly view such interactions as a sign of corruption, rather than expertise.”

To this end, Rosenbaum sets out to find a “reasoned approach” to physician-industry interactions that acknowledges both the benefits of the collaboration, while recognizing the risks of bias involved. To lay the foundation of her paper, she starts off by describing the release of “controversial new cholesterol guidelines” in November 2013, which expanded the target population for preventative statin therapy. The criticism against the guidelines was swift, she noted from experience, from those who believed that the primary beneficiary of these guidelines would be the pharmaceutical industry.

In a New York Times op-ed, for example, a cardiologist and another physician and industry critic argued that making more patients eligible for statin therapy would “benefit the pharmaceutical industry more than anyone else.” Objecting to using statins for primary prevention, they drew from a medical journal article that one of them had coauthored emphasizing the frequency of side effects. This frequency turned out to be exaggerated, necessitating an erratum in the journal. Yet no one was questioning the editorialists’ credibility in the public press; rather, the editorialists challenged the credibility of the guideline writers: “The American people deserve to have important medical guidelines developed by doctors and scientists on whom they can confidently rely to make judgments free from influence, conscious or unconscious, by the industries that stand to gain or lose.”

Rosenbaum’s article provides a counter to such industry-skeptics, who are often amazingly uncritical in their dismissal of important industry-collaborative efforts. “One could argue that people also deserve to know that statins are, in many cases, the best drugs we have to prevent cardiovascular disease and that the committee had spent 5 years reviewing the evidence to identify the patients who would benefit most,” she writes.

She also outlines the steps taken to avoid the introduction of conflicts into the guidelines, given that 7 of the 15 committee members did have current or previous industry ties:

  • First, the members with current industry ties were not allowed to vote on the quality of the evidence statements or the recommendations, and none of the members without industry ties have developed ties since the guidelines were published.
  • Second, because of past concerns about conflicts, the committee used an independent contractor, appointed by the National Heart, Lung, and Blood Institute, to choose the studies on which the recommendations were based.
  • Third, though the controversy centered on primary prevention for people whose 10-year risk of a cardiovascular event exceeds 7.5%, the guidelines make clear that this cut point is merely a threshold for initiating discussion about statins, rather than a mandate to start treatment with one.
  • Fourth, the resulting guidelines are actually no boon to companies selling patent-protected drugs: most statins are available in generic versions, and the guidelines recommend against using (patent-protected) drugs that improve lipid levels but that hadn’t, at the time of guideline writing, been proven to improve outcomes.

Despite laying out the facts behind the guidelines, Rosenbaum notes: “the greater difficulty is that whereas a rational approach to regulating industry interactions requires careful parsing of such nuances, our general feelings about industry interactions, as the easy dismissal of the statin guidelines illustrates, can be impervious to relevant detail.”

On cue, a response to Rosenbaum’s article in Health News Review did indeed seem impervious to the details: “Dr. Rosenbaum makes a nice try at reinterpreting financial conflicts between physicians and pharma, but however one twists and turns it, the dots still reconnect into dollar signs.” The article’s conclusion? “Don’t trust what comes out of a drug company (or medical journals?) and verify, verify, verify.”

One of the many interesting points Rosenbaum raises in her article is that discussions of bias have been limited to the financial. In fact, she argues, bias is perhaps strongest and most risky when scientists or doctors have a professional stake in the outcomes of their research: discovering a breakthrough, developing novel treatments, publishing journal articles, etc.

Rosenbaum does not gloss over the harm greed can cause, outlining the misleading Vioxx studies that minimized the drug’s risks and ultimately resulted patient harm. However, she believes an overemphasis on a drug’s risks can be harmful as well. “Vioxx’s continued relevance to our management of physician–industry interactions lies in the lingering impression that some companies will do anything to profit, even if it means suppressing evidence to patients’ detriment — an impression reinforced by subsequent Big Pharma scandals,” states Rosenbaum.

Perhaps the most memorable two paragraphs of Rosenbaum’s article are when she pinpoints the reasons behind many deep set suspicions of industry: 

For the many physicians whose primary interactions with industry are of the marketing variety, the beneficial nature of other industry relationships may lack emotional traction. We see the attractive pharmaceutical reps in our offices. We eat the lunches (or walk away hungry). Our patients, heeding the “Ask your doctor” mantra of drug ads, request medications we may not believe should be prescribed. We hear that our prescription habits are being monitored so that we can be targeted for better sales. And we observe colleagues, their suits sharp, their skin tanned from a free Hawaiian vacation, their children’s college education covered, and though we may take some satisfaction in eschewing pharmaceutical largesse, still, for some, the resentment burns.

By contrast, how visible to us are physician-scientists whose National Institutes of Health grant applications go unfunded, and who therefore increasingly rely on industry support for their laboratories? Does it cross our minds, when we prescribe statins after a myocardial infarction, how much collaboration between industry and physician-scientists was required to develop them? When we read an editorial by someone who is “conflict-free,” do we wonder whether someone else whose industry ties prevented authorship might have had unique expertise to share? Of course, the fact that the benefits of industry interactions are often imperceptible does not excuse the more easily imagined offenses. But the visibility imbalance helps explain why our aversion to certain industry behaviors deeply colors our overall impressions of industry.

Read Rosenbaum's full article in the New England Journal of Medicine here.  


May 08, 2015

Pharmaphobia: How the Conflict of Interest Myth Undermines American Medical Innovation


Long a champion of physician and industry collaboration, Thomas Stossel, M.D., has published a new book entitled Pharmaphobia: How the Conflict of Interest Myth Undermines American Medical Innovation. In it, Stossel, a distinguished Harvard hematologist and researcher, decries the conflict of interest movement as detrimental to medical progress and ultimately the patients who would benefit from new, innovative therapies.

Writing about conflicts of interest has been an increasingly surefire way to get published—the Journal of the American Medical Association even has its own conflict of interest category. What’s often missing from both sides of the mostly academic “COI” debate, however, is a relation back of nebulous concepts to what is important: tangible medical innovations and patient well-being.

One of the reasons Dr. Stossel’s writing is so engaging is that he bucks this trend by illustrating in plain language what is at stake. “Physician-industry interactions have been critical to the development of a large percentage of the medical products that allow physicians to prevent heart attacks, cure cancers, and restore mobility to the elderly,” he writes.

Over the course of my career, medicine and industry have together made spectacular progress against diseases. Cardiovascular deaths are down 60 percent, HIV has been converted from a death sentence to a chronic disease, and cancer mortality is at a historic low. Despite such progress and the role of physician-industry interactions in fomenting it, physicians are reducing or severing their relationships with biopharmaceutical and medical device companies out of fear that their patients will mistakenly view such interactions as a sign of corruption, rather than expertise.

In addition to the large amount of ink being spilled in academic journals on COI, Stossel characterizes a number of recent legislative measures as being similarly “pharmophobic.” He points specifically to the medical device excise tax and the Physician Payments Sunshine Act, which requires pharmaceutical and device companies to report any payments to physicians and teaching hospitals of more than $10. These payments are reported on a publicly accessible website, “with minimal explanations,” he notes, which “stigmatiz[es] relationships that are critical to the development and dissemination of new medical products.”

“[O]ne of the highest-paid physicians in the Sunshine database is a world-famous vascular surgeon who received royalties for his invention of multiple aneurism repair devices,” Stossel illustrates. Similarly, "Paul Offit, who invented the rotavirus vaccine that is believed to have reduced the incidence of hospitalizations for rotavirus-induced diarrhea by more than 85 percent among U.S. toddlers since its addition to the childhood-vaccine schedule in 2006, is often maligned for his industry ties." Stossel concludes: “Such cases, along with research grants for clinical trials, dominate the largest payments documented under the Sunshine Act. They are unequivocally beneficial and should not be stigmatized in this manner.”

Dr. Stossel’s book also aims to illustrate just how important private industry has been to these amazing breakthroughs. Again, he is the perfect spokesman for this. “I’ve done medical research for most of my career, and people say that I’ve been successful at it," he notes. “I hope that this research will save lives someday, but only drug and device companies can make that happen.”

He writes:

Publicly supported academic research certainly advances medical knowledge. But converting that knowledge to clinical benefits isn’t straightforward. Helping patients justifies public research funding, but obtaining such funding depends far more on impressing grant review committees with the novelty and virtuosity of research than with its practical medical applications. I know, because following these precepts has certainly contributed to my success. I have had continuous government research funding for over 45 years, have published research papers in prestigious scientific journals, won prizes, and been elected to elite scientific societies. Yet no one has lived one second longer or better as a direct result of my research.

But regulations, largely stemming from the conflict of interest movement has only served to impede medical innovation. “Regulations always slow things down, and compliance and enforcement divert precious funds from research and development,” states Dr. Stossel. “It takes on average 16 years and costs over $2 billion to get a new drug approval by the FDA.” This delay matters:

For patients desperate for new treatments and cures, such delays can be lethal. Marketing restrictions mean doctors don’t learn about drug and device advances. Delays or prevention of potentially innovation-promoting relationships between researchers and industry have been documented. The myth that device and drug development isn’t difficult and expensive encourages enactment of taxes on companies and calls for price controls. Both inhibit innovation.


Dr. Stossel stands as a rare counter to the COI movement, and provides years of experience and patient-centered arguments to back it up.  Pharmaphobia: How the Conflict of Interest Myth Undermines American Medical Innovation is out now and available here. Also, read  a Q&A with Stossel about his book.

In full disclosure, Thomas Sullivan, Editor of Policy and Medicine is listed in the preface to Pharmaphobia, he receives no remuneration from the sales of this book or his work with Dr. Stossel.  


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