Life Science Compliance Update

July 26, 2016

FDA: Draft Guidance - Procedures for Evaluating Appearance Issues and Granting Authorizations for Participation in FDA Advisory Committees

FDA released draft guidance to deal with what it describes as "appearance issues" that make advisory committee members appear to lack impartiality. This applies even to those who do not have financial interests and relationships that are conflicts of interests. If an appearance issue exists, FDA will weigh the member's participation against the concern that a reasonable person may question the integrity of the FDA's decision. This is a troubling development for the constitutional freedom of association, especially if professionals are going to be forced to recuse themselves for merely the appearance of a conflict.

The guidance comes after Public Citizen filed a Freedom of Information Act lawsuit against FDA in a bid to get unredacted copies of advisory committee members' curriculum vitae -- which describe their education, qualifications and previous experience -- posted on the agency's website.

Michael Ortwerth, FDA's director of the Advisory Committee Oversight and Management Staff, said in an FDA Voice blog post that a lack of understanding about the agency's selection and evaluation process has resulted in public confusion and misunderstanding. He explains the guidance contains: "the circumstances that FDA considers when determining whether an appearance issue may exist. We evaluate the circumstances and assess whether the interests, relationships, or circumstances would cause a reasonable person with knowledge of the relevant facts to question the advisory committee member's impartiality in the matter before the committee."

As an example: "if an advisory committee member serves on the board of directors of a nonprofit organization and that organization receives donations from the sponsor that is presenting before the committee, we review the details of the donation to determine whether the member should be cleared for service on the advisory committee."

He notes this is not finalized, however: "The draft guidance is being issued for public comment before we issue a final guidance. Under Federal law, FDA is not permitted to disclose confidential information provided by advisory committee members related to appearance issues. But we are specifically requesting comments on whether the agency should request that advisory committee members voluntarily disclose if they have been granted an appearance authorization."


Members of FDA's advisory committees are subject to Government-wide standards of ethical conduct regulations in addition to Federal conflict of interest laws. Even where a member has no financial interests that would require her to refrain from participating in an advisory committee meeting ("recuse" herself) under Federal conflict of interest laws, the member may be disqualified from participation under the Government-wide Federal regulation at 5 CFR § 2635.502 ("section 502") if she has interests or relationships that may create the appearance that she lacks impartiality on the issue before the advisory committee.

Section 502 gives FDA and other agencies significant flexibility and discretion in deciding whether a member with an appearance issue should participate in a particular matter. Under section 502, when a member has an appearance issue, FDA may authorize the member to participate in the advisory committee meeting based on a determination, made in light of all relevant circumstances, that the interest of the Government in the member's participation outweighs the concern that a reasonable person may question the integrity of the agency's programs and operations. If FDA does not issue an authorization, the individual may not participate in the meeting or the portion of the meeting involving the particular matter relevant to the appearance issue.

In determining whether to grant an authorization under section 502 to a member with an appearance issue, FDA balances the agency's interest in access to the advice of qualified experts to make important public health decisions with the need to avoid serious questions about the member's impartiality. Section 502 places the initial burden of identifying potential appearance issues on the member. It also gives the member the initial responsibility to recuse herself where she determines that the circumstances would cause a reasonable person with knowledge of the relevant facts to question her impartiality in the matter, unless she informs FDA of the issue and receives authorization from FDA to participate. FDA has the discretion to make independent determinations about whether a member has an appearance issue and to decide whether to grant her an authorization to participate once an appearance issue is identified.

Screening to Identify Possible Appearance Issue

In preparation for an advisory committee meeting involving a particular matter, members report to FDA any interests related to the subject matter of the meeting. These interests are reported on the Confidential Financial Disclosure Report. Although the Confidential Financial Disclosure Report Form primarily focuses on current financial interests, it also asks for information about past financial interests that directly relate to the products or issues to be considered at the meeting, and any other interests or relationships that might give rise to an appearance issue.

A member may seek assistance from FDA in completing this form. In completing this form, a member is required to report anything that would create an appearance issue not otherwise disclosed on the Form. The member may make a threshold judgment as to whether the information would cause a reasonable person to question her participation, and so inform the agency. FDA reviews the completed Confidential Financial Disclosure Report for each member in advance of every committee meeting to determine whether an appearance issue exists. As part of this review, FDA may ask for clarification about reported interests or about interests not reported but of which FDA may otherwise be aware.

What Circumstances May Create Appearance Issue?

Section 502 specifically lists certain interests and relationships that could create an appearance issue. It also includes a "catch-all" provision, which covers any other circumstances that may cause a reasonable person to question the member's impartiality. Once these circumstances raise a concern regarding the impartiality of the member, FDA considers the totality of the circumstances when determining to grant an authorization.

  • "Direct and Predictable Effect" on the Current Financial Interest of a Member of the Advisory Committee Member's Household

Under section 502, the following scenario would raise a potential appearance issue: where the particular matter coming before the advisory committee is likely to have a "direct and predictable effect" on the current financial interest of a member of the advisory committee member's household.

  • A Person or Entity with Whom the Member has a "Covered Relationship" is or Represents a "Party to the Matter"

Under section 502, the following scenario would also raise a potential appearance issue: where a person (or entity) with whom the advisory committee member has a "covered relationship" is or represents a "party to the matter" coming before the advisory committee. Both "covered relationship" and "party to the matter" are described in the guidance document.

  • Other Circumstances that May Raise a Question about the Member's Impartiality

Examples include broadly stated, "matters of general applicability". "Particular matters of general applicability" involve potential changes to regulations or agency guidance, or other broad topics such as policy-making and decisions that affect an entire class of products, such as reviewing labeling changes for an entire class of products. Particular matters of general applicability tend to raise fewer appearance issues than particular matters involving specific parties. However, the agency may require members to recuse from particular matters that do not involve specific parties, based on the concern that the member's impartiality reasonably may be questioned under the circumstances.

Other listed examples include relationships that are not technically "covered relationships" such as social relationships. Past financial interests ending more than one year before the meeting that suggest a close relationship with the sponsor or involvement with the product(s) before the committee was also a part of the "catch-all" provision.

Example from FDA Guidance

Scenario: The advisory committee is reviewing the safety and efficacy of a product. The meeting is a particular matter involving specific parties with one party to the matter ("the sponsor").

Example: The member's primary employment is as a dean of the medical school at a large university. The member reported that her employer has a multi-year grant from the product sponsor (i.e., the sponsor of the product that will be reviewed and evaluated at the advisory committee meeting) and the grant is not related to the product before the committee. This is an interest or relationship that could cause a reasonable person to question the member's impartiality.

Factors FDA Would Consider in Determining Whether or Not to Grant a Section 502 Authorization For the Member to Participate in the Meeting:

  • Whether the member receives any personal funding or remuneration from the grant (if not, this would weigh in favor of a section 502 authorization);
  • Size and diversity of the range of products made or under development by the sponsor providing the grant funding to the employer (the larger and more diverse the range of products the more this would weigh in favor of a section 502 authorization);
  • Whether the member's employer relies solely, or principally, on this grant from the sponsor (if not, this would weigh in favor of a section 502 authorization);
  • Whether the matter before the committee is considered sensitive or controversial (matters that are typical and routine without controversy would weigh in favor of a section 502 authorization);
  • Whether the member has expertise that is important to the committee's work and others with comparable expertise have conflicts or appearance issues more extensive than the member's (if so, this would weigh in favor of a section 502 authorization);
  • If there is a need for multiple experts in a field (if so, this would weigh in favor of a section 502 authorization).


It comes to a point, that this is becoming ridiculous. The examples FDA uses would disqualify any physician whose institution is working on a research grant for the sponsor for a different product. Good luck in finding medical school faculty. The scenarios of "appearance" could go on forever, if the FDA wants to spend their time on fruitless exercises, then this is the guidance for you. Would not their time be better evaluating products then hunting through CV's for hidden conflicts.

March 22, 2016

ProPublica: Tying Open Payments Physician Data to Medicare Part D Data

ProPublica is once again trying to make a "correlation equals causation" argument between payments made to physicians and their prescribing patterns. ProPublica is arguing that an analysis they performed showed that "doctors who receive payments from the medical industry do indeed tend to prescribe drugs differently than their colleagues who don't."

They are arguing that doctors who received more than $5,000 from companies in 2014 had the highest brand-name prescribing percentages, giving an example that among internists who received no payments, the average brand-name prescribing rate was 20%, compared to about 30% for those who received more than $5,000.

What is interesting in the data is the absolutely high number ranging from 70-90% of generic medications both physicians who don't work with industry and those who do work with industry. In both groups a vast majority of their prescriptions were for generic medications which generally over 20+ years from initial development. A slight increase in the use of branded drugs should be considered a good thing for patients. As it is well known that it takes many years for physician adoption to newer therapies.

However, there is no proof that industry payments sway doctors to prescribe particular drugs, or even a particular company's drugs, just that payments are "associated with an approach to prescribing that, writ large, benefits drug companies' bottom line." There may be much more to the story if ProPublica found a link between payments made to physicians and the brand of drug they prescribed.

It is important to note, as laid out in more detail below, that physicians consider many factors when deciding which medications to prescribe. Some physicians treat patients for whom few, or no, generics are available; for example, doctors who treat patients with HIV/AIDS. Other physicians specialize in patients with complication conditions who have tried generic drugs with no success.

One physician that we discussed this with independently, thought it was appalling that there was no consideration of patient outcomes. If the physicians patients benefiting from the branded drugs then there should be credit given to those physicians working with industry.

According to Holly Campbell, spokeswoman for the Pharmaceutical Research and Manufacturers of America, "many factors" affect doctors' prescribing decisions and according to a 2011 survey of physicians, more than ninety percent of physicians felt that "a great deal of their prescribing was influenced by their clinical knowledge and experience."

Ms. Campbell believes that by working together, "biopharmaceutical companies and physicians can improve patient care, make better use of today's medicines, and foster the development of tomorrow's cures." Physicians provide insights and feedback to inform companies about their medicines to improve patient care and patient health.

By meeting with industry professionals, doctors get a chance to better understand the drugs that exist, the outcomes, and any side effects. Dr. Amer Syed of Jersey City, NJ, said that he does look at the quality of medication and the benefits patients get from taking the medicine before deciding what to prescribe, stating that his "whole vision of practice is to keep the patients out of the hospital."


ProPublica examined Medicare Part D prescription data and pharmaceutical and medical device company payment data (found under Open Payments) to measure any relationship between industry payments and brand-name prescribing.

Interestingly, when ProPublica broke down the data by payment type, they found that physicians who received speaking payments had higher rates of brand-name prescribing than those who received other types of payments, and that physicians whose only payments were for meals had lower rates of brand prescribing than those who received other payments. This may speak to the idea that physicians who prescribe the same drug over and over again do so because they are comfortable with it, they know the results and the side effects, and since they know the drug so well, the company asks them to speak for them.

There is a huge "but" with the data cited to by ProPublica. The data does not consider whether branded drugs, for the indications prescribed, are superior to generic medications (or combinations of generic drugs), nor whether patient outcomes were different. Data that confirms safety and efficacy are much more likely to describe branded products than they are generics.

We are big proponents, however, of giving credit where credit is due. In this case, ProPublica did a nice job describing the circular relationship between companies and doctors. They published a quote by Dr. Kim Allan Williams, Sr., the president of the American College of Cardiology, who stated the more physicians learn and understand a new drug's "differentiating characteristics," the more likely they are to prescribe it, and the more they prescribe it, the more likely they are to be selected as speakers and consultants for the company. According to Dr. Williams, "that dovetails with improving your practice, and yes, you are getting paid to do it."

Dr. Williams also explained that new drugs are somewhat responsible for the significant decrease in cardiovascular mortality in the past three decades, and that the relationship between doctors and companies in cardiology may be driving that progress.

October 07, 2015

Study Looks At How Many Industry Boards of Directors Have Academic Affiliations


Conflict of interest rules for the medical community have been in the spotlight lately, though they typically center around rules that prohibit or restrict physicians from enjoying lunch on behalf of a pharmaceutical company or stocking their office with pens. A new study conducted by researchers from the University of Pittsburgh School of Medicine and published in the British Medical Journal recently decided to look at conflicts of interest from a different perspective: they looked at how many for-profit healthcare company positions were occupied by people with academic affiliations.

These researchers analyzed public disclosures of all publicly traded United States healthcare companies listed in the NASDAQ and NYSE in January 2014 that specialized in pharmaceuticals, biotechnology, medical equipment, and providing healthcare services. The researchers defined an academic medical or research affiliation as “a formal position at a US medical school, affiliated teaching hospital, or health system; overseeing research university; or medical research institute with a medical school partnership” and they further classified individuals with academic affiliations as either leaders, professors, or trustees, as each group holds a different set of responsibilities to their academic institutions that pose unique conflicts with their obligations as for profit company directors.

The study found that 41% of the companies surveyed had one or more academically affiliated board of directors members in 2013. Several of those board of directors members held positions on more than one company’s board of directors: the study found that 279 academically affiliated directors held a total of 309 healthcare directorships, which is less than 10 percent of all total healthcare directorships.

Over half of academically affiliated directorships were held by individuals with clinical training, predominately in internal medicine or related subspecialties, the most common of which were general internal medicine, cardiology, and oncology.

The compensation these academically affiliated board of directors members received for their board of director position varied widely, ranging from zero dollars to over one million dollars, with the median compensation being $193,000. In addition to their monetary compensation, many board of directors members received major stock in their company.

After looking at all of the data, study co-author Timothy Anderson, MD, does not believe that the existence of academically affiliated board of directors members is necessarily a problem in and of itself. Instead, he thinks that it simply poses legitimate questions for initiating a discussion about conflict of interest with academic institutions, healthcare companies, and their interrelationships.

When questioned about the link and possible problems, Dr. Anderson stated, "Our view is not to pass judgment. We wanted to paint that landscape of how diverse these sorts of relationships are. Some may be quite beneficial and some might be quite concerning, but until we really understand what relationships exist, it is hard for the medical and academic community to have a good discussion about what we should do to minimize the risks and maximize the benefits of these collaborations." He continued on, noting that a one-size-fits-all approach will not work to manage all of the relationships, but instead, a more open approach is warranted to avoid losing the public’s trust.

Anderson thinks that the way the Sunshine Act solely focuses on physicians and attempts to expose their minute financial interests might be misguided and results in oversight of academic professionals and their loyalties. The study focused on the fact that academics who sit on the board of a for-profit company have duties of loyalty both to the academic organization that employs them, as well as to the shareholders of the company whose board they sit on. The concern of the study and the researchers behind it are that those loyalties have the opportunity to conflict at times, placing the academic board member in a precarious position.   

The study acknowledged that “there is no doubt that collaboration between academic institutions and industry has led to profoundly important clinical trials, drug development, and translational research initiatives, although the role and necessity of academically affiliated directors in facilitating these projects is unclear and undocumented” and that academic institutions can benefit from having their staff members and faculty as representatives in corporate board rooms, forging fundraising or research partnerships.

The study further recognized that one of the difficulties in developing guidelines to monitor the competing interests is that the potential harms vary depending on the individual’s primary academic duties. Certain academics may be in a position, both academically and professionally as a board of director, to balance the potential conflicts of interest and will successfully benefit both organizations with their knowledge and expertise.

However, because the end result of the study advocates for “additional review, regulation, and, in some cases, prohibition when conflicts cannot be reconciled,” it is worth keeping an eye on potential movement in this area. It is likely only a matter of time before someone, or a group of people, speak up and ask for more strict regulation on academics who serve as a member of the board of directors for for-profit companies.   This would be unfortunate as both organizations can benefit from the other in expertise and developing much needed cures.


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