Life Science Compliance Update

108 posts categorized "Medical Journals"

April 10, 2014

JAMA Opinion Article Looks for Bias in Academic Health Systems and Board Membership

The Journal of the American Medical Association (JAMA) recently published an opinion piece entitled "Conflict of Interest Policies for Academic Health Systems Leaders Who Work with Outside Corporations." As we have come to expect from JAMA, the article was packed with generalizations, but low on real facts and relevant data to support their claims.

JAMA has been active in the past few months, recently taking aim at continuing medical education (CME). There, the authors so desperately rummaged for "conflicts of interests" that they failed to differentiate between promotion companies and accredited medical education companies. The article ignored the firewalls, standards, and oversight that have been in place for several years to prevent the alleged bias the authors claimed.

Apparently JAMA has moved on. The new article focuses on academic health system leaders – presidents, vice presidents, deans, CEOs – who work for outside corporate entities. The authors argue that these higher-ups who are involved in financial and business decisions have fiduciary responsibilities that "preclude a paid relationship with an outside entity…unless a case can be made that there is a compelling institutional interest in the leader's service in such a role, or if the role with the outside organization is outside the scope of the leader's role at the academic health system."

JAMA provides an interestingly specific illustration of such a carve-out from their calls for an end of all corporate relationships. The article notes, that an "example of a compelling institutional interest" would be "the leader's role as a founder of an academic health system start-up company based on his or her intellectual property."

The lead author, Etta D. Pisano, Vice President for Medical Affairs Dean, College of Medicine; Professor of Radiology, Medical College of South Carolina, ironically fits neatly into her exception:

"Recently Dr. Pisano co-founded her own company, NextRay, Inc., which will commercialize a device she and the other cofounders invented, a technology which creates medical images using x-rays through diffraction enhanced imaging which provides superior image quality at a dose that is substantially lower than is currently available" (available here).

While her efforts in the medical device arena are laudable, it begs the question: who does Dr. Pisano expect to buy her company, and how is this not a commercial interest? She speaks to the "very difficult" issue of conflict of interest in the article, but enjoys one with her own company.

This is not the first time that JAMA has been engaging in the very behavior it spends an article decrying. In the JAMA CME piece, JAMA criticized medical education companies' policy of sharing data, when JAMA's own policy includes sharing data with undisclosed third parties.

It is tough to take an article too seriously when the authors are actively doing the opposite of what they are writing. In the most innocuous case it suggests that JAMA does not have a full grasp on the material it offers. The fact that the article includes the specific carve-out, however, would tend to imply that the authors knew the deal.

Study

The article looked at the 50 largest pharmaceutical companies and compiled data on the prevalence of AMC leaders on the companies’ boards of directors. The study found that 19 of the 47 companies with public data on governance had at least one board member who concurrently held a leadership position at an AMC, including “16 of 17 (94%) US companies.” In total, “[f]orty-one board members had AMC leadership positions in 2012, receiving a mean financial compensation for board membership of $312,564 (excluding the 6 industry executives).” 

Jama pics

Putting aside the issues of credibility, the main issue with the opinion piece is that it raises questions, but does not attempt to answer them. The article states: "Having a fiduciary responsibility to 2 separate entities is at best a very difficult situation. Will the leader direct business inappropriately to the outside company on whose board he or she sits? Will the leader inappropriately use information about the institution he or she leads to influence decisions by the outside corporation?"

Questions about someone's personal conflict of interest are easy to raise, but the article provides no real-world context. Furthermore, the authors fail to include any evidence of academic institutions ever being harmed by an executive's roles with corporate entities.

We argue that there are actually many benefits to such a relationship with outside entities:

  • The current landscape for academic medical centers is bleak. Many academic centers cannot compete in efficiency with local for-profit medical centers. An academic leader who understands the private sector could provide industry practice to an otherwise inexperienced entity.
  • Relationships could help academic centers recruit and retain faculty members by providing them with the opportunity to engage in outside interests, enabling them to identify new research scholarship topics and apply their theories.
  • Relationships can increase the potential outside financial support for the institution—either directly or indirectly—through joint ventures and the activities and networking of faculty members in the larger community, including the business community.
  • Often companies are crucial to translate academic research into actual medication that can benefit patients.

 

March 04, 2014

FDA Draft Guidance: Distributing Scientific and Medical Publications on Unapproved New Uses — Recommended Practices

A new draft guidance document released by the U.S. Food and Drug Administration (FDA) aims to clarify the ways in which a pharmaceutical or medical device manufacturer may use scientific and medical literature to promote its products, even if the literature doesn't conform to the product's FDA-approved uses. FDA's guidance forms a checklist of sorts that companies will need to check against each instance of literature they wish to promote.

FDA's new draft guidance document, Distributing Scientific and Medical Publications on Unapproved New Uses — Recommended Practices, is meant to provide life science companies with a checklist for making sure they stay within the acceptable limits of promotion of scientific and medical publications. The guidance is a revision of a 2009 draft guidance, Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices. As noted by Regulatory Focus, that guidance came under fire from life science companies, which argued that it restricted their ability to "promote the public health" by distributing scientific information informing the safe and effective use of their products.

In an accompanying statement, the FDA stated that it's currently working on additional guidance on scientific exchange, responding to unsolicited requests for off label information, and interactions with formulary committees. 

This draft guidance shows that the agency is getting the message that it must conform its policies and practices to the First Amendment," said Coalition for Healthcare Communication Executive Director John Kamp in a released statement. "Manufacturers should be able to distribute truthful information – in the form of journal articles, medical textbooks and practice guidelines."

In an Industry Leaders Alert, Kamp also stated: "These actions, combined with recent guidance on social media and a new study on the effectiveness of current warnings on TV commercials, suggest that the FDA is serious on updating critical marketing policies, perhaps in recognition of the First Amendment challenges it faces is defending current policy."

"While these are small steps forward, they are significant nonetheless and will enable more reasonable communication between regulated companies and medical professionals, leading to more efficient and effective patient care. The new draft guidance also supports our case with CMS that journal reprints and reference textbooks should be exempt from reporting under the Sunshine Act."

Public Comment

The Draft Guidance is open for public comment for 60 days, until May 2, 2014. Submit electronic comments to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register.

I. INTRODUCTION AND BACKGROUND

In 1997, Congress passed the Food and Drug Administration Modernization Act (FDAMA). Section 401 of FDAMAdescribed certain conditions under which a drug or medical device manufacturer could choose to disseminate medical and scientific information that discusses unapproved uses of approved drugs and cleared or approved medical devices to "health care professionals and certain entities, including pharmacy benefits managers, health insurance issuers, group health plans, and Federal or State governmental agencies," without such dissemination being considered as evidence of the manufacturer's intent that the product be used for an unapproved new use. Among those conditions was the expectation that the manufacturer of the product would seek FDA approval for the unapproved new use referenced in the disseminated literature. With this condition, Congress again recognized the important public health value of FDA premarket review and approval.

FDA's 2009 guidance was intended to provide drug and medical device manufacturers and their representatives with recommendations on distributing scientific or medical information on unapproved uses to health care professionals and health care entities, without such dissemination being considered as evidence of the manufacturer's intent that the product be used for an unapproved new use.

The 2009 guidance, consistent with the objectives of section 401 of FDAMA (which was no longer law), recognized that the public health may benefit when health care professionals receive truthful and non-misleading scientific or medical publications on unapproved new uses.This information can be particularly important given that a health care professional can generally choose to use or prescribe an approved or cleared medical product for an unapproved use, if the off-label use is appropriate based on his or her judgment. The narrow "safe harbor" recommended in the guidance was also consistent with FDA's continued belief that FDA premarket review and approval are critical to public health.

FDA is revising its 2009 guidance on good reprint practices in response to stakeholder questions about its application to scientific and medical reference texts and CPGs that include or may includeinformation on unapproved uses. This draft guidance provides recommendations for scientific journal articles, scientific or medical reference texts, and CPGs in separate sections, tailored to each type of publication. Consistent with longstanding FDA policy and practice, if manufacturers distribute scientific or medical publications as recommended in this guidance, FDA does not intend to use such distribution as evidence of the manufacturer's intent that the product be used for an unapproved new use.

Although this draft guidance, like the 2009 guidance, recognizes the value to health care professionals of truthful and non-misleading scientific or medical publications on unapproved new uses, it also continues to recognize that this information is in no way a substitute for the FDA premarket review process, which allows FDA to be proactive, rather than reactive, in protecting the public from unsafe or ineffective medical products. FDA is issuing this revised draft guidance to enable the public to provide comments on the proposed approach.

II. RECOMMENDED PRACTICES

Often scientific and medical information concerning the safety or effectiveness of a medical product's unapproved new use may be published in scientific or medical journal articles, scientific or medical reference texts, and/or in CPGs. These publications are available from their publishers or other distribution channels, but have also been commonly distributed by manufacturers to health care professionals and health care entities.

Sections A, B, and C, below, provide specific guidance for scientific and medical journal articles, scientific and medical reference texts, and CPGs, respectively. FDA recommends that manufacturers employ the following practices if they choose to disseminate scientific and medical publications that include or may include information on unapproved new uses of approved, cleared, or 510(k) exempt products.

A. Scientific or Medical Journal Articles

If a manufacturer who chooses to distribute scientific or medical journal articles that include information on unapproved/uncleared uses of its product(s) does so in accordance with the recommendations of this guidance, FDA does not intend to use that distribution as evidence of the manufacturer's intent that the product(s) be used for an unapproved new use.

A scientific or medical journal article that includes information on unapproved uses and is distributed by manufacturers should first have been published by an organization that has an editorial board that uses experts who have demonstrated expertise in the subject of the article under review by the organization. Experts should be independent of the organization and should review and objectively select, reject, or provide comments about proposed articles. Also, the organization should adhere to a publicly stated policy of full disclosure of any conflict of interest or biases for all authors, contributors, or editors associated with the journal or organization.

Additionally, the scientific or medical journal article distributed by a manufacturer should:

1. Be peer-reviewed and published in accordance with the peer-review procedures of the organization.

2. Be in the form of an unabridged reprint or copy of an article.

3. Contain information that describes and addresses adequate and well-controlled clinical investigations that are considered scientifically sound by experts with scientific training and experience to evaluate the safety or effectiveness of the drug or device. In the case of devices, significant investigations other than adequate and well-controlled studies, such as meta-analyses, if they are testing a specific clinical hypothesis, and journal articles discussing significant non-clinical research (such as well-designed bench or animal studies) may be consistent with this guidance.

4. Be disseminated with the approved labeling or, in the case of a medical device reviewed under section 510(k) of the FD&C Act (21 U.S.C. 360(k)), labeling for the indications in the product's cleared indications for use statement, for each of the manufacturer's products that is included in the distributed article.

5. Be disseminated with a comprehensive bibliography, when such information exists, of publications discussing adequate and well-controlled clinical studies published in scientific journals, medical journals, or scientific texts about the use of the drug or medical device covered by the information disseminated (unless the information already includes such a bibliography).

6. Be disseminated with a representative publication, when such information exists, that reaches contrary or different conclusions regarding the unapproved use—especially when the conclusions of articles to be disseminated have been specifically called into question by another publication.

7. Be distributed separately from the delivery of information that is promotional in nature. Similarly, while reprints may be distributed at medical or scientific conferences in settings appropriate for scientific exchange, reprints should not be distributed in promotional exhibit halls or during promotional speakers' programs.

A scientific or medical journal article that explains a use of a manufacturer's product and is distributed by, or on behalf of, that manufacturer must not:

1. Be false or misleading. characterized as definitive or representative of the weight of credible evidence derived from adequate and well-controlled clinical investigations if it is inconsistent with the weight of credible evidence or if a significant number of other studies contradict the conclusions set forth in the article; should not have been withdrawn by the journal or disclaimed by the author; and should not discuss a clinical investigation that FDA has previously informed the company is not adequate and well-controlled.

2. Contain information recommending or suggesting use of the product that makes the product dangerous to health when used in the manner suggested.

To be consistent with the recommended practices described in this guidance, a scientific or medical journal article regarding an unapproved use that is distributed by a manufacturer should not:

1. Be in the form of a special supplement or publication that has been funded, in whole or in part, by one or more of the manufacturers of the product that is the subject of the article.

2. Be marked, highlighted, summarized, or characterized by the manufacturer, in writing or orally, to emphasize or promote an unapproved use. (This recommendation does not preclude providing the disclosures discussed elsewhere in this guidance.)

3. Be primarily distributed by a drug or device manufacturer; rather, it should be generally available in bookstores or other independent distribution channels (e.g., subscription, Internet) where periodicals are sold.

4. Be written, edited, excerpted, or published specifically for, or at the request of, a drug or device manufacturer.

5. Be edited or significantly influenced by a drug or device manufacturer or any individuals having a financial relationship with the manufacturer.

6. Be attached to specific product information (other than the approved product labeling or the product's cleared indications for use statement).

The scientific or medical journal reprint should be accompanied by a prominently displayed and permanently affixed statement disclosing:

1. The drug(s) or device(s) included in the journal reprint in which the manufacturer has an interest

2. That some or all uses of the manufacturer's drugs or devices described in the information have not been approved or cleared by FDA, as applicable to the described drug(s) or device(s).

3. Any author known to the manufacturer as having a financial interest in the manufacturer or in a product of the manufacturer that is included in the journal article, or who is receiving compensation from the manufacturer, along with the affiliation of the author, to the extent known by the manufacturer, and the nature and amount of any such financial interest of the author or compensation received by the author from the manufacturer.

4. Any person known to the manufacturer who has provided funding for the study.

5. All significant risks or safety concerns associated with the unapproved use(s) of the manufacturer's product(s) discussed in the journal article that are known to the manufacturer but not discussed in the article.

The following types of journal reprints are examples that would not be considered consistent with the recommended practices outlined in this guidance:

  • Letters to the editor
  • Abstracts of a publication
  • Reports of healthy volunteer studies
  • Publications consisting of statements or conclusions but which contain little or no substantive discussion of the relevant investigation or data on which they are based

B. Scientific or Medical Reference Texts

Scientific or medical reference texts diagnosis, pathophysiology and treatments, pharmacology, surgical techniques, and other scientific or medical information). Like journal articles, scientific or medical reference texts often contain information about unapproved use(s) of drugs and devices. However, because these reference texts are considerably longer than journal articles, and generally address a wide range of topics, FDA believes that it is appropriate to make specific recommendations for distribution of reference texts that differ somewhat from the recommendations for journal articles. If a manufacturer who chooses to distribute reference texts that include information on unapproved/uncleared uses of its product(s) does so in accordance with the recommendations of this guidance, FDA does not intend to use that distribution as evidence of the manufacturer's intent that the product(s) be used for an unapproved new use.

A scientific or medical reference text that is distributed in its entirety by a manufacturer should:

1. Be based on a systematic review of the existing evidence.

2. Be published (in print or electronic format) by an independent publisher, not substantially dependent on financial support from drug or medical device manufacturers, who publishes scientific or medical educational content for health care professionals and students.

3. Be the most current version.

4. Be authored, edited, and/or contributed to by experts who have demonstrated expertise in the subject area.

5. Be peer-reviewed by experts with relevant medical or scientific expertise and published in accordance with the scientific or medical reference text peer-review procedures of the publisher, which should be easily accessible or available upon request.

6. Be sold through usual and customary independent distribution channels (e.g., booksellers, subscription, Internet) for medical and scientific educational content directed at health care professionals and students.

7. Be distributed separately from the delivery of information that is promotional in nature. Similarly, while scientific or medical reference texts may be distributed at medical or scientific conferences in settings appropriate for scientific exchange, they should not be distributed in promotional exhibit halls or during promotional speakers' programs.

8. Contain a prominently displayed and permanently affixed statement identifying the distributing manufacturer and disclosing that some of the uses for drugs and/or devices described in the reference text might not be approved or cleared by FDA. The statement should also disclose that the author(s) of some chapters also might have a financial interest in the manufacturer or its products, unless the manufacturer has verified that none of the authors for the reference text has a financial interest in the manufacturer or a product being written about. This statement should be placed by sticker, stamp, or other similar means on the front cover of the textbook.

9. In situations where a reference text is distributed in its entirety but one or more individual chapters of that reference text devote primary substantive discussion to an individual product or products of the manufacturer distributing it, be disseminated with the approved product labeling for each such product or, in the case of a medical device reviewed under section 510(k) of the FD&C Act (21 U.S.C. 360(k)), labeling for the indications in the product's cleared indications for use statement.

If, in lieu of an entire scientific or medical reference text, a manufacturer distributes an individual chapter(s) that includes information on unapproved/uncleared uses of the manufacturer's product(s), the chapter(s) should:

1. Come from a scientific or medical reference text that follows the recommendations for complete scientific or medical reference texts in this guidance, except that the individual chapter(s) should bear the prominently displayed and permanently affixed statement described below for use on individual chapters, rather than the recommended statement for texts distributed in their entirety.

2. Be unaltered/unabridged and extracted directly from the scientific or medical reference text in which it appears.

3. When necessary to provide context, be disseminated with other unaltered/unabridged chapters extracted directly from the same scientific or medical reference text, such as chapters which provide related or supportive information.

4. Contain a prominently displayed and permanently affixed statement identifying the distributing manufacturer and disclosing:

(a) The drug(s) or device(s) addressed in the individual chapter(s) in which the manufacturer has an interest;

(b) That some or all uses of the manufacturer's drugs and/or devices described in the attached information have not been approved or cleared by FDA, as applicable to the described drug(s) or medical device(s);

(c) Any author known to the manufacturer as having a financial interest in the manufacturer or in a product of the manufacturer that is included in the individual chapter(s), or who is receiving compensation from the manufacturer, along with the affiliation of the author, to the extent known by the manufacturer, and the nature and amount of any such financial interest of the author or compensation received by the author from the manufacturer;

(d) All significant risks or safety concerns associated with the unapproved use(s) of the manufacturer's products discussed in the individual chapter(s) that are known to the manufacturer but not discussed in the chapter(s).

This statement should be placed by sticker, stamp, or other similar means on the front page of each chapter.

5. Be disseminated with the approved labeling, or, in the case of a medical device reviewed under section 510(k) of the FD&C Act (21 U.S.C. 360(k)), labeling for the indications in the cleared indications for use statement, for each of the manufacturer's products that is included in the distributed chapter(s).

A scientific or medical reference text, or an individual chapter, that explains a use of a manufacturer's product and is distributed by, or on behalf of, that manufacturer must not:

1. Be false or misleading.

2. Contain information recommending or suggesting use of the product in ways that make the product dangerous to health when used in the manner suggested therein.

To be consistent with the recommended practices described in this guidance, a scientific or medical reference text, or an individual chapter, that is distributed should not:

1. Be primarily distributed by a drug or device manufacturer; rather, it should be generally available in bookstores or other independent distribution channels (e.g., subscription, Internet) where textbooks are sold.

2. Be edited or significantly influenced by a drug or device manufacturer or any individuals having a financial relationship with the manufacturer.

3. Be marked, highlighted, summarized, or characterized by the manufacturer, in writing or orally, to emphasize or promote an unapproved use. (This recommendation does not preclude providing the disclosures discussed elsewhere in this guidance.)

4. Be written or published specifically at the request of a drug or device manufacturer.

5. Be abridged or excerpted in any particular manner

6. Be attached to specific product information (other than the approved product labeling or the product's cleared indications for use statement).

C. Clinical Practice Guidelines

CPGs are statements that include recommendations intended to help clinicians make decisions for individual patient care, including in circumstances where there are few or no approved drugs or devices indicated for the patient's condition or the approved therapies have not proven successful for the individual. A CPG may be much longer and often covers a wider range of topics than a journal article. FDA believes that it is appropriate to make specific recommendations for manufacturer distribution of CPGs that include information on unapproved new uses of that manufacturer's approved or cleared products that differ somewhat from the recommendations for journal articles. These recommendations are set forth below, along with additional recommendations that incorporate the Institute of Medicine's (IOM's) standards for CPG "trustworthiness." These "trustworthiness" standards, among other things, ensure that CPGs are informed by a systematic review of evidence and an assessment of the benefits and 458    harms of alternative care options.

If a manufacturer who chooses to distribute CPGs that include information on unapproved/uncleared uses of its product(s) does so in accordance with the recommendations of this guidance, FDA does not intend to use that distribution as evidence of the manufacturer's intent that the product(s) be used for an unapproved new use.

Drug and medical device manufacturers wishing to disseminate CPGs that discuss unapproved or uncleared new uses of products that they market should disseminate only those guidelines that are "trustworthy," as described below. In keeping with the IOM standards, to be considered "trustworthy," a CPG should at minimum:

1. Be based on a systematic review of the existing evidence.

2. Be developed by a knowledgeable, multidisciplinary panel of experts and representatives from key affected groups.

3. Consider important patient subgroups and patient preferences.

4. Be based on an explicit and transparent (publicly accessible) process by which the CPG is developed and funded that minimizes distortions, biases, and conflicts of interest.

5. Provide a clear explanation of the logical relationships between alternative care options and health outcomes, provide clearly articulated recommendations in standardized form, and provide ratings of both quality of evidence and the strength of recommendations.

6. Be reconsidered and revised when important new evidence warrants modifications of recommendations.

Manufacturers wishing to distribute a "trustworthy" CPG in its entirety should:

1. Ensure that the most current version of the CPG is disseminated.

2. Distribute the CPG separately from the delivery of information that is promotional in nature. Similarly, while a CPG may be distributed at medical or scientific conferences in settings appropriate for scientific exchange, the CPG should not be distributed in promotional exhibit halls or during promotional speakers' programs.

3. Ensure that the CPG contains a prominently displayed and permanently affixed statement identifying the distributing manufacturer and disclosing that some of the uses of drugs and/or devices described in the CPG might not be approved or cleared by FDA. The statement should also disclose that the author(s) of some sections might have a financial interest in the manufacturer or its products, unless the manufacturer has verified that none of the authors for the CPG has a financial interest in the manufacturer or a product being written about. This statement should be placed by sticker, stamp, or other similar means on the front page of the CPG.

4. In situations where a CPG is distributed in its entirety but one or more individual sections of that CPG devotes primary substantive discussion to an individual product or products of the manufacturer distributing it, be disseminated with the approved product labeling for each such product or, in the case of a medical device reviewed under section 510(k) of the FD&C Act (21 U.S.C. 360(k)), labeling for the indications in the product's cleared indications for use statement.

If, in lieu of an entire CPG, a manufacturer distributes an individual section(s) that includes information on unapproved/uncleared uses of the manufacturer's product(s), the section(s) should:

1. Come from a CPG that satisfies the recommendations set forth in this guidance, including the standards for "trustworthiness," except that the section should bear the prominently displayed and permanently affixed statement described below for use on individual sections, rather than the recommended statement for CPGs distributed in their entirety.

2. Be unaltered/unabridged and extracted directly from the CPG in which it appears.

3. When necessary to provide context, be disseminated with other unaltered/unabridged sections extracted directly from the same CPG, such as sections which provide related or supportive information.

4. Contain a prominently displayed and permanently affixed statement identifying the distributing manufacturer and disclosing:

(a) The drug(s) or device(s) addressed in the individual section(s) in which the manufacturer has an interest;

(b) That some or all uses of the manufacturer's drugs and/or devices described in the attached information have not been approved or cleared by FDA, as applicable to the described drug(s) or medical device(s);

(c) Any author known to the manufacturer as having a financial interest in the manufacturer or in a product of the manufacturer that is included in the individual section(s), or who is receiving compensation from the manufacturer, along with the affiliation of the author, to the extent known by the manufacturer, and the nature and amount of any such financial interest of the author or compensation received by the author from the manufacturer;

(d) All significant risks or safety concerns associated with the unapproved use(s) of the manufacturer's products discussed in the individual section(s) that are known to the manufacturer but not discussed in the section(s).

This statement should be placed by sticker, stamp, or other similar means on the front page of each section.

5. Be disseminated with the approved labeling, or, in the case of a medical device reviewed under section 510(k) of the FD&C Act (21 U.S.C. 360(k)), labeling for the indications in the cleared indications for use statement, for each of the manufacturer's products that is included in the distributed section(s).

A CPG or individual section(s) of a CPG that explains a use of a manufacturer's product and is distributed by, or on behalf of, that manufacturer must not:

1. Be false or misleading.

2. Contain information recommending or suggesting use of the product in ways that make the product dangerous to health when used in the manner suggested therein.

To be consistent with the recommended practices described in this guidance, a CPG or individual section of a CPG that discusses unapproved new uses of a manufacturer's product should not:

1. Be primarily distributed by a drug or device manufacturer, but should be generally available through other independent distribution channels (e.g., subscription, Internet).

2. Be edited or significantly influenced by a drug or device manufacturer or any individuals having a financial relationship with the manufacturer.

3. Be marked, highlighted, summarized, or characterized by the manufacturer in writing or orally, to emphasize or promote an unapproved use. (This recommendation does not preclude providing the disclosures discussed elsewhere in this guidance.)

4. Be written or published specifically at the request of a drug or device manufacturer.

5. Be abridged or excerpted in any particular manner.

6. Be attached to specific product information (other than the approved product labeling or the product's cleared indications for use statement).

January 07, 2014

CME: ACCME Responds to JAMA and Pew Studies

The Accreditation Council of Continuing Medical Education (ACCME), the main accrediting body for CME courses, responded to two reports dealing with transparency in physician-industry relationships. ACCME President and CEO Murray Kopelow, MD voiced his concerns with the Journal of the American Medical Association (JAMA) as well as the Pew Charitable Trusts' Pew Prescription Project.

JAMA Study

As a background, on December 18, JAMA published a report seeking to explore the relationship between drug/device companies and "medical communication companies" (MCCs). Among the study's conclusions were that MCCs receive more funds than other types of CME providers and that they collect personal data from healthcare providers to share with third parties.

We pointed out several flaws with the study in our article on the report. Importantly, JAMA failed to differentiate between accredited medical education companies, which may not promote on behalf of pharma and "medical communication companies," which are not accredited and may. The report also disingenuously categorized charitable contributions of pharmaceutical companies as medical education payments, and identified two not-for-profit foundations as MCCs. Furthermore, JAMA criticized medical education companies' policy of sharing data, when JAMA's own policy includes sharing data with undisclosed third parties.

In addition to JAMA's inaccuracies, they failed to mention the rigorous accrediting process conducted by ACCME. Murray Kopelow explained ACCME's issues with the study in an interview with MeetingsNet.

"The article is wrong about ACCME-accredited providers from the beginning," he states. "There are no ACCME-accredited providers that are 'supported mainly by drug and device companies' and that 'develop prelaunch and branding campaigns." He continued: "Organizations involved in marketing or promotion are not even eligible for ACCME system accreditation. Thus, medical communication companies are not part of accredited CME in the ACCME system."

By merging medical communication companies and medical education companies in the article, Kopelow argues that JAMA presented a "misleading, inaccurate, and imbalanced picture of accredited continuing medical education and the stringent requirements in place to safeguard its independence." Kopelow described these safeguards ACCME in place to ensure that medical education companies are not providing promotional services to industry:

Before an organization can become accredited, it must meet the ACCME eligibility requirements. The organization cannot be involved in producing, marketing, distributing, or re-selling healthcare products or services used by, or on, patients. ACCME does a corporate review to ensure that the organization does not fall into the definition of commercial interest…

If there is a question as to whether a company is acting as a communication company, the ACCME does a corporate review to ensure that the organization does not fall into the definition of commercial interest. No organization that is accredited within the ACCME system can be owned or controlled by an ACCME-defined commercial interest. 

The authors of the JAMA article imply that continuing medical education companies are funded almost entirely by industry. In fact, the majority of CME produced by medical education companies is not commercially supported. According to ACCME's annual report, only 18 percent of activities presented by ACCME-accredited providers received commercial support in 2012.

Kopelow also disagreed with the article's implications about a lack of transparency regarding this support: "Details of industry grants in the form of commercial support to all accredited providers have been available for review by the ACCME for decades. Every written agreement for every commercial support grant in all ACCME-accredited CME is available to the ACCME for review."

Kopelow made a number of other important points regarding the JAMA article, as well as CME transparency.

Is CME being "tainted by promotion"?

Kopelow believes "marketing masked as education," as the interviewer called it, is a concept that has been made obsolete by the ACCME's Standards for Commercial Support of CME, as well as the myriad of other government, professional, and industry laws, rules, regulations, and guidelines put into place over the last three decades. Accredited CME is based on professional practice gaps. It is designed without input from industry with respect to identification of need, determination of educational objectives, selection and presentation of content, selection of persons and organizations in a position to control the content, selection of educational methods, and the evaluation of the activity. The management of all funds is strictly regulated and all the terms and conditions of the commercial support are laid out in a written agreement. The ACCME Standards are recognized nationally, by the profession, by the regulators, and by the government as safeguarding the independence of CME.

While Kopelow acknowledges that pre-existing relationships that speakers and authors have with companies does present a threat to the independence of accredited CME, this problem was addressed in 2004 with the addition of the ACCME's Standards regarding the identification and resolution of conflict of interest. All those involved in the development and presentation of CME activities must disclose relevant financial relationships with commercial interests. Accredited CME providers must implement strategies for identifying and resolving any conflicts of interest that are identified through this process.

In the ACCME's opinion, JAMA also glazed over the most important aspect of CME: the actual content. All the recommendations involving clinical medicine in a CME activity must be based on evidence that is accepted within the profession of medicine as adequate justification for their indications and contraindications in the care of patients. All scientific research referred to, reported, or used in CME in support or justification of a patient care recommendation must conform to the generally accepted standards of experimental design, data collection, and analysis. Providers are not eligible for ACCME accreditation or reaccreditation if they present activities that promote recommendations, treatment, or manners of practicing medicine that are not within the definition of CME, or known to have risks or dangers that outweigh the benefits or known to be ineffective in the treatment of patients. An organization whose program of CME is devoted to advocacy of unscientific modalities of diagnosis or therapy is not eligible to apply for ACCME accreditation.

Is the Sunshine Act's CME exemption a loophole to allow industry to influence CME content?

Kopelow states, "[t]here is no back door allowing industry to influence the content of accredited CME." The CME exemption in Open Payments is not an exemption from ACCME, but rather "recognition that the commercial support of accredited CME does not establish a relationship with authors or speakers. It also shows that the government recognizes the value of the Standards for Commercial Support: Standards to Ensure Independence in CME Activities in safeguarding the independence of accredited CME."

While there are in fact loopholes allowing medical communication companies to bypass ACCME's policies, these companies are not accredited. "All accredited providers in the ACCME system, including the publishing and education companies, are held to the same high standards," and "under [ACCME's] rules, industry can provide no input whatsoever regarding content or speakers for accredited CME activities."

JAMA's editorial implies that industry regularly pays for physicians to fly to Maui for CME trips. Is this allowable?

"Under ACCME rules, industry is not allowed to make direct payment to physician learners or speakers with respect to an accredited CME event. Providers cannot use commercial support to pay the personal expenses of learners or their family for any reason whatsoever. Commercial support may be used to pay for faculty travel and expenses—but again, payments cannot be made directly from industry to physicians."

_____

In addition to JAMA's deceptive data, Kopelow took issue with their misrepresentation of the 2007 Senate Finance Committee Report. While JAMA used various out-of-context quotes to conclude that abuse continued to be rampant in 2013, the report concluded that pharma was in fact doing a better job complying with fraud and abuse laws back in 2007. Kopelow states that since 2007, improvement has been even greater: "the ACCME took the concerns of the Senate Finance Committee very seriously and in response we enhanced our monitoring efforts. We accelerated the accreditation enforcement process to ensure more timely and rigorous oversight, particularly of noncompliance issues related to independence."

Finally, Kopelow addressed JAMA's assumption that medical communication companies collect healthcare providers' personal information to share with third parties. Kopelow stated, again, that accredited medical education companies are not MCCs: "We can only speak to rules regarding accredited providers and we cannot comment on the practices of medical communication companies, as they are not accredited in our system. The ACCME has rules requiring accredited providers to track participation and to explain to participants if the information is going to be shared."

Pew Report

In mid-December, the Pew Charitable Trust issued a report that indicated the ACCME's "Standards for Commercial Support" were not sufficient to ensure transparency in physician/industry relationships or to manage conflicts of interest in academic medical centers. We stated that the Pew recommendations merely restate their longstanding condemnation of accredited CME: that any financial support from commercial interests—no matter how stringent the restrictions on its use—renders the curriculum irrevocably tainted.

ACCME President and CEO Murray Kopelow, MD again answered questions and defended the rigorous standards in place. Indeed, Kopelow calls the successful and widespread adoption and implementation of ACCME 2004 Standards for Commercial Support: Standards to Ensure Independence in CME Activities by the ACCME and the CME community "one of the great successes of medical education in the 21st century":

We believe the [Standards] are the only common set of educational standards shared by multiple professions, specifically medicine, pharmacy, nursing, optometry, dentistry, and physician assistants. They are a fundamental building block of nursing, medicine, and pharmacy's Joint AccreditationTM—which is the only interprofessional education accreditation system in the world…

The 2004 Standards were approved by each of the ACCME's seven member organizations, which represent the profession of medicine and include physician licensing and credentialing bodies.

The Standards have become a national model. The ACCME Standards have been recognized across the health professions. The Accreditation Council for Pharmacy Education has adopted the Standards. In addition, the fields of dentistry, family medicine, nursing, optometry, osteopathy, and physician assistants base their accreditation standards on the Standards.

The federal government recognizes the value of the ACCME Standards in safeguarding independence and the role of accredited CME in supporting public health. The FDA has leveraged the accredited CE system in support of the [Risk Evaluation and Management Strategies] REMS for Extended-Release and Long-Acting Opioid Analgesics. Under this REMS, the FDA is requiring opioid manufacturers to provide grants for CME. This is one example of how commercially supported CME can address a critical public health initiative. In addition, CMS recognized the value of the SCS in safeguarding independence when it exempted accredited CME from its rule regarding physician payments reporting.

The ACCME Standards are recognized nationally, by the profession, by the regulators, and by the government as safeguarding the independence of CME.

Kopelow also expressed disagreement over the accuracy of Pew's claims and the relevancy of Pew's data, which, as we noted in our article, come from 1988, 1992, and 2001 statistics:

[T]he Pew report says, "… central [CME] offices do not prevent companies from specifying the topic of the course or which academic department should receive the funds." Of course they prevent companies from specifying the topics. ACCME says, "There is no reason for the CME provider to request suggestions for speakers or topics from commercial interests—since it is unacceptable to act upon their suggestions. CME providers can receive commercial support from industry. CME providers cannot receive guidance, either nuanced or direct, on the content of the activity or on who should deliver that content."

Pew also says, "...studies suggest that industry funding of continuing medical education tends to bias topic choices and content in favor of the sponsors' products and therapeutic areas."  Pew cites studies from 1988, 1992, and 2001. The first ACCME SCS were adopted in 1992. The current version was adopted in 2004. The ACCME commissioned a review of this literature in 2008 looking for the evidence in support of this Pew hypothesis. We could not find it. We do not think it is appropriate to infer that there is research evidence for Pew's opinions.

Pew's report recommends "[i]n general, continuing medical education should not be supported by industry." Where industry funding is "nonetheless being considered," however, Pew advises several additional safeguards beyond compliance with the ACCME, including:

  • Creating an undesignated, or blinded, pool of money contributed by multiple companies for the purpose of supporting an institution's CME program.
  • Requiring that commercially funded courses be supported by at least two companies and that no single company contribute more than 50 percent for a given program.
  • Requiring that physicians personally contribute some money toward industry-supported courses.
  • Requiring that industry-supported courses take place in non-resort locations.

 

Kopelow concluded: "we do not have plans for incorporating those recommendations into our requirements."

Conclusion:

Placing unfounded doubts in the minds of physicians over disclosure policies, as the Pew and JAMA articles do, is counterproductive and creates concern and confusion relating to the application of valuable information. As recently as late December, the Food & Drug Administration (FDA) distributed a presentation entitled: FDA Role in Continuing Medical Education (CME), which determined that: "CME (is an) essential part of staying informed as a practitioner," and that "FDA has (an) emerging role in using CME as one component of our work to improve safe use of medical products."

Last month, the CME Coalition responded to the JAMA and Pew reports, calling them "inaccurate…and disingenuous" and "dangerous to America's health" respectively. The ACCME's response reinforces these criticisms. The authors in both articles unfortunately make no effort to elaborate on (1) the content of the CME programs they attack, (2) the FDA mandates that the sponsor control the content so that speakers do not talk about off-label use or non-evidence-based application of products, or (3) the rigors of complying with the ACCME.

 

 

December 18, 2013

Continuing Medical Education (CME): Flawed JAMA Report Blurs Line Between “Medical Communication Companies” and Accredited “Medical Education Companies”

Today, the Journal of the American Medical Association (JAMA) published a brief report (Medical Communication Companies and Industry Grants) as well as an editorial in order to explore "the financial relationships between MCCs and drug device companies." The authors use a mixture of outdated figures, hyperbole, and blatant untruths to piece together their articles, which, according to CME Coalition Senior Advisor, Andrew Rosenberg, contain "so many inaccuracies and examples of unfounded innuendo" that "it is a challenge to enumerate them all."

JAMA has decided not to make the report available to the public, but we have compiled the report's content.

JAMA erroneously interchanges Medical Communication Companies with Medical Education Companies:

Grant Donations 2010

   

Roche/Genentech 

106,916,052 

Merck 

99,481,044 

Pfizer 

89,520,722 

Abbott 

69,518,593 

Eli Lilly 

54,767,686

Bristol-Myers Squibb 

43,570,166 

Amgen 

43,383,578 

AstraZeneca 

35,628,747 

Sanofi-Aventis 

34,404,149 

GlaxoSmithKline 

29,658,381 

Medtronic 

26,125,342 

Astellas 

11,905,202 

Forest Laboratories 

9,400,372 

Shire 

3,987,736 

Total* 

658,267,770 

Note the JAMA Article has the total of 657,643,322 – excel addition did not match their total.

 

 
     
       

The most obvious sign of invalidity comes from the fact that the authors confuse "Medical Education Companies" with MCCs. Medical education companies are regulated by the Accreditation Council for Medical Education (ACCME). The two are different and practice different lines of work with different sets of rules. Medical education companies, such as those represented by the CME Coalition, are held to strict standards outlined by nationally recognized medical accreditation bodies designed to eliminate the potential for commercial influence in the content or provision of science-based curricula to physicians and other medical professionals.

The authors are correct that "Medical Communications Companies" work with pharmaceutical companies to help position products for the market, but medical education companies are regulated against doing the same. By lumping the two together, JAMA falsely inflates its data. Rosenberg added, "While the supposedly data-driven JAMA editorial writers assert that '(CME) that is tainted by promotion … can lead to inappropriate prescribing that can harm patients and waste money,' they acknowledge in the same paragraph that there is no proof of any such taint due to an 'absence of a systematic review of CME materials.'"

 

Funds 

 

Grants 

 

Top Medical Education Company Recipients 

Awarded 

MEC % 

Number 

MCC% 

Medscape 

20,315,730 

12 

96 

4.6 

Postgraduate Institute of Medicine 

11,274,544 

7 

91 

4.4 

Research to Practice

10,375,787 

6 

93 

4.5 

National Comprehensive Cancer Network (NCCN) 

8,878,434 

5 

96 

4.6 

Medical Education Resources 

7,749,794 

5 

40 

1.9 

PER Group 

6,566,321 

4 

95 

4.6 

Network for Continuning Medical Education 

4,704,447 

3 

16 

0.8 

Educational Concepts Group 

4,464,220 

3 

52 

2.5 

Imedex 

3,158,472 

2 

70 

3.4 

Med-IQ 

3,430,104 

2 

19 

0.9 

Clinical Care Options 

2,941,810 

2 

6 

0.3 

Pri-Med 

2,884,215 

2 

33 

1.6 

National Foundation for Infectious Disease 

2,499,475 

2 

19 

0.9 

Institute for Medical Education and Research 

2,493,452

1 

21 

1 

Curatio CME Institute 

2,466,663 

1 

11 

0.5 

Primary Care Network 

2,423,370 

1 

14 

0.7 

Scepter 

2,347,355 

1 

13 

0.6 

Discovery Institute for Medical Education 

2,232,059 

1 

18 

0.9 

         

Total* 

101,206,252 

59 

803

38.7 

*JAMA article had total at 101,566,252 – again Excel addition did not match their data.

       

Upon word of the JAMA article's release, the National Comprehensive Cancer Network (NCCN), which is reported as a "Medical Communication Company" in the article, reached out to instruct the authors that this was, in fact, not true. They stated: "As a not-for-profit alliance of 23 of the world's leading cancer centers, NCCN is a Medical Professional Specialty Society, not a Medical education or communications company (MECC)." National Foundation for Infectious Disease is not a medical education or communications company either.

Inaccurate Data:

 

 

 

Grant Recipients by Amount and Number of Grants Received 

   
 

Funds 

 

Grants 

 
 

Amount 

Percent 

Number 

Percent 

Medical Education, Medical Communications, and Consulting Companies 

170,803,675 

26 

2,077 

11

         

Academic Medical Centers and Universities 

140,928,677 

21 

5,427 

28 

         

Disease-targeted advocacy organizations 

95,769,466 

15 

4,033 

21 

         

Professional Medical Associations 

83,949,432 

13 

2,063 

11 

   

 

   

Other Organizations 

80,745,433 

12 

1,697 

9 

         

Professional Associations 

37,009,540 

6 

1,427 

8 

Hospital Systems and Independent Providers 

26,339,514 

4 

2,040 

11 

         

Research Organizations 

22,097,585 

3 

468 

2 

   

 

   

Total 

657,643,322 

100 

19,272 

100 

The Report disingenuously categorizes the reported charitable contributions of several pharmaceutical companies as medical education payments in order to bolster the appearance of their magnitude. Furthermore, two of the organizations listed in the report and portrayed as "Medical Communication Companies" are not-for-profit foundation and do not operate as medical education companies.

It is worth noting that the authors report their conclusion as simply: "Medical communication companies receive substantial support from drug and device companies."

In a statement from Pharmaceutical Research and Manufacturers of America (PhRMA) Senior Vice President Matthew Bennett

"As patients, we all want our physicians and nurses to be current on the latest medical technologies, including new medicines. Ongoing CME, closely regulated by accrediting bodies and government, is a valuable part of physician education – especially regarding innovative treatments for which there may be limited clinical experience – as well as an important asset to improving patient care. These contributions should not be overlooked by research and opinion pieces that exclude these important facts.

"The JAMA study and editorial make a number of assertions the authors describe as 'indirect industry influence,' but fail to mention strong industry rules and accreditation standards that limit such practices. For example, the ACCME (Accreditation Council for Continuing Medical Education) Standards for Commercial Support require that if a pharmaceutical company provides a grant for CME, the company is not permitted to provide content or help select speakers. Moreover, the PhRMA Code on Interactions with Healthcare Professionals expressly prohibits a pharmaceutical company from providing any advice or guidance to the CME provider, even if asked by the provider, regarding the content or faculty for a particular CME program funded by the company.

Misunderstanding and/or Distorting 2007 Senate Finance Committee Report:

The JAMA editorial lays the foundation for the entire report with a carefully plucked quote from 2007. The quote is taken from the 2007 Finance Committee Report, where the Committee noted that they "became aware through reports that pharmaceutical companies were routinely using educational grants to help build market share for the newer and more lucrative products....In 2004, Warner Lambert paid $430 million to settle claims involving off-label promotion of Neurontin."

However, the authors left out the crux of the Finance Committee Report findings: that "the pharmaceutical industry is paying increased attention to educational grants and its compliance with fraud and abuse laws," and that "major drug companies have limited the direct involvement of field sales representatives and sales and marketing departments in the educational grant-making process" (p. 15). The Committee staff also found "some promising trends in pharmaceutical manufacturers' use of educational grants," such as companies adopting "corporate policies that, on their face, do not allow educational grants to be awarded for unlawful purposes."  Moreover, the report recognized that, "major pharmaceutical companies now conduct their educational grants activities in a way that is less likely to involve the direct transfer of remuneration from the company to physicians" (p. 16-17).

Not only did the Committee Report come out almost seven years ago, but the favorable remarks from the Finance Committee came only a short time after the Accreditation Council for Medical Education (ACCME) updated their Standards for Commercial Support in order to ensure Independence. In addition, the PhRMA Code on Interactions with Healthcare Professionals, which was strengthened in 2008, contains detailed provisions specific to the conduct and training of speakers. Under the PhRMA Code, company decisions regarding the selection of healthcare professionals are based on defined criteria such as medical expertise, reputation, knowledge and experiences in a particular therapeutic area, and communication skills. Many other subsequent settlements have enhanced the number of firewalls in place to prevent the potential for bias suggested in the articles.

JAMA Criticizes Data Policy of Medical Education Companies Despite Using the Same Policy:

JAMA strangely takes issue with online privacy in continuing medical education programs, despite the fact that JAMA's own policy includes sharing data with undisclosed third parties. "Physicians who interact with MCCs should be aware that all require personal data and some share these data with third parties," the article states. Ignoring the fact that internet "cookies" are as plentiful as google hits (and that JAMA itself discloses personal information to third parties), apparently JAMA did not do proper research in this part of their report either. NCCN responded to the accusation by saying: "NCCN does not sell or provide personal information to third parties for marketing purposes" as do all of the websites they listed. Also a quick check of the privacy policies of the authors websites Institute of Medicine as a Profession and Informuarly reveal both collect personal data or emails and neither has a privacy policy. Not sure why physicians should "trust" them and not medical education websites with defined policies.

Interestingly, JAMA takes issue with continuing medical education being provided in non-computer locations as well, the author positing that she would want "to go to Maui to discuss common issues in primary care." First, that practice of paying for physician attendance at accredited events has been strictly prohibited for almost years. Second, if taking CMEs online at home doesn't cut it for JAMA in terms of solitary learning environments, what does?

Additional Hypocrisy in the JAMA Report:

JAMA's report concludes by revealing that the authors made no attempt whatsoever to evaluate if commercial bias actually exists in any of the programs they reported on. After publishing a report full of stale data, demands that someone "clos[e] loopholes" without a description of the loopholes to be closed, and repeated rallying cries against "for-profit" industries that have saved countless lives, this aspect was not too surprising.

Most disturbingly about the report is the blatant hypocrisy. According to the AMA annual report, in 2010 JAMA, a subsidiary of AMA, received over $25 million dollars in advertising revenue. Both JAMA and the medical education companies receive funds from the pharmaceutical industry for support of programs.

The report's findings indicate solely that "[m]edical communication companies receive substantial support from drug and device companies. The authors unfortunately make no effort to elaborate on the content of the CME programs they attack, or the rigors of complying with the ACCME.

This is part of a long standing campaign that JAMA has undertaken to undermine access to medical information outside of medical journals. The report and editorial are disingenuous and JAMA should be ashamed of themselves for such blatant hypocrisy.

Placing unfounded doubts in the mind of physicians over data disclosure policies like those of JAMA is counterproductive and creates concern and confusion relating to the application of valuable information.

Disclosure: Thomas Sullivan an author of this report is a principle in Rockpointe and the Potomac Center for Medical Education, medical education companies which work exclusively on accredited education. They receive grants from pharmaceutical and device companies which demonstrate the supporting companies' commitment to educating health care professionals to improve healthcare.

Continuing Medical Education (CME): Association of Clinical Researchers and Educators Calls Out Flawed JAMA Study

The following is taken from a press release from the Association of Clinical Researchers and Educators

This week the Journal of the American Medical Association (JAMA) published a "brief report" and editorial on medical communications companies and industry grants. This paper is reminiscent of the parental admonition of "do as I say, not as I do".  In the article, the authors comment that in 2010 private medical communications companies received $100 million from industry.  According to the AMA annual report, in 2010 JAMA, a subsidiary of AMA, received over $25 million in advertising revenue.  Both JAMA and the medical communications companies receive funds from the pharmaceutical industry.

In addition, we found several errors in the report and editorial:

Inclusion of foundation funds and nonprofit giving in the aggregate, citing industry websites to assess  that medical communication companies received over $100 million in industry support;

Alluding that current practice includes paying physician attendees travel at accredited events  for resorts like Maui when that practice has, for many years been strictly prohibited;

The citation of the rationale of the January 2007 study by the Senate Finance Committee Report, rather than the conclusion of the study, which runs counter to the arguments of the authors. The Committee report found that, "the pharmaceutical industry is paying increased attention to educational grants and its compliance with fraud and abuse laws," and that "major drug companies have limited the direct involvement of field sales representatives and sales and marketing departments in the educational grant-making process."

Two of the organizations listed in their report and portrayed as Medical Communications Companies are not-for-profit foundations and do not operate as medical education companies;

Misrepresenting Medical Education Companies who receive educational grants from manufacturers and are regulated by the ACCME with Medical Communications Companies who are regulated by FDA and work directly for manufacturers;

Disparaging the data policies of medical education companies as sharing data with 3rd parties as unique when in fact JAMA's own policy includes sharing data with undisclosed 3rd parties.

ACRE requests JAMA to severely edit or withdraw the articles due to factual errors and omissions.

The credibility at JAMA is at stake. The editor should be held responsible for such glaring errors on the report and the subsequent editorial.

The JAMA research paper shows that pharmaceutical companies give a proportionate number of grants to private providers of education, which, in fact is similar to the practice of the US government which awards  grants to private companies to provide education

We believe that private medical education companies can help to bring cutting edge clinical science to our practitioners.  Recently, the FDA recognized accredited CME as a valuable way of reaching today's busy physicians.  Those who make their living support efforts to educate physicians should be praised for their work, not discredited by ivory tower academics.

We believe that placing doubt in the mind of physicians over disclosure policies like those of JAMA is unproductive and creates concern and confusion relating to the application of valuable information.

Founded in 2009, the Association of Clinical Researchers and Educators is a collection of academic and private practice physicians and researchers dedicated to promoting innovation in modern medicine.

October 18, 2013

Knee Replacement Surgery’s Savings to Society

With all of the scrutiny that physicians have faced over the last several years with respect to their involvement and collaboration with industry, many forget about the critical improvements in patient health that such relationships foster.

For example, a recent study published in The Journal of Bone & Joint Surgery suggests that patients over time can reap nearly $40,000 on average in "societal savings" -- the money they earn from being able to work instead of being on disability -- from total knee-replacement surgery, which is more than the roughly $21,000 cost of the procedure.

In fact, the study found that all the total knee replacements performed in 2009 in the United States saved an estimated $12 billion in lifetime societal savings with most of that benefitting patients and employers, reported Orthopedics Today.

"We know that when a knee replacement is done on patients at the appropriate time, it adds tremendous value to their lives. It gets them back to work and back to their families. It improves their quality of life and allows them to be productive and active again," John R. Tongue, MD, American Academy of Orthopaedic Surgeons (AAOS) past-president, stated in an AAOS press release. "But until now, that value has been hard to quantify. This study allows patients to see the big picture of the effect on their daily lives and in the long term."

Tongue noted that four (4) additional studies analyzing the financial benefits of other orthopedic procedures are in the pipeline.

Tongue and colleagues used a Markov model to estimate the direct and indirect cost savings for the more than 600,000 total knee replacements (TKR) for end-stage knee osteoarthritis (OA) during 2009 in the United States. They measured direct costs, which included expenditures for surgical and nonsurgical end-stage knee OA treatment, as well as indirect costs, including lost wages, lower earnings and disability payments, according to the abstract.

The investigators found a lifetime overall net benefit for TKR of $18,930 per patient. To determine this, they subtracted the mean increase in indirect lifetime savings of $20,635 that they found from the $39,565 societal savings associated with reduced indirect costs from TKR that they calculated.

Eighty-five percent of the savings accrued were from "increased employment and earnings," and the other 15% in savings was from a reduced number of disability payments and fewer missed days of work, Tongue and colleagues concluded.

"With the new model we created for this study, we have opened the door to evaluate societal benefit for other types of health care services as well, which is truly exciting," Lane Koenig, PhD, a study author and health care economist, from Rockville, Md., stated in the release. "The benefit of successful treatment of bone and joint conditions in the long term is known by the patients who've been through it, but these data offer evidence on the societal effects that will add to the conversation people are having about improved, cost-conscious health care."

Interestingly, the study comes at a time when the costs of procedures such as knee and hip replacements come under scrutiny, particularly in the era of comparative effectiveness researcher. In other words, many have begun to question whether expensive surgeries actually save patients and society money versus other alternatives such as physical therapy. For example, another study last month found a staggering disparity between what hospitals charge for the operations, and little connection between price and the quality of outcome, reported CNBC.

This study, however, may dispel concerns about the costs of these procedures. The research will bring clarity to those who have questioned the value of knee replacements and change the conversation about whether such surgery is worth it.

Mary Ann Tuft, a 78-year-old who runs Tuft & Associates, a Chicago-based boutique executive search firm, underwent total knee replacement in 2005 after years of pain.

"I found it difficult to walk down the block," Tuft said. She began avoiding networking events such as cocktail parties "because you stand all the time," she added. "After a decade, I had enough of it, and I just knew that I had to do something." Tuft raved about the results of her surgery, saying she's much more mobile and barely aware of the fact that she has an artificial joint. "I probably wouldn't have been able to function" much longer, she said.

"This is eight years later, and my business has probably grown three or four times since," said Tuft, adding that the firm's annual billings top $1 million. "We have more business now that we've ever had."

 

October 10, 2013

The Significant Physician Contribution to the Development of Medical Devices

With increased calls for transparency in physician-industry relationships, including the Physician Payment Sunshine Act and clinical trials, it becomes important for the public to understand the extent of physician's contributions to science, medicine and the improvement of healthcare and patient's quality of life.

For example, relationships between physicians and industry have led to life-saving innovations, such as steerable cardiac catheters and certain artificial heart valves. Physician innovators also developed the first reliable pacemakers in the 1950s and 1960s, with medical device makers later introducing additional refinements.

Physicians hold a unique position as innovators in medical industry, particularly with medical devices. Use of medical devices usually requires a high degree of specialized knowledge and skill. Physicians on the leading edge of medical knowledge may find it necessary at first to build the tools they need, if those tools do not yet exist. Perhaps for this reason, device manufacturers consider physician-researchers to hold a central role in the industry and often pursue ideas from the same physician-entrepreneurs over time

Previous research has shown the various contributions physicians make to medicine. For example, one study showed that 57% of existing drugs' new uses originated through clinical practice, rather than research. Another study showed that 80% of the scientific instrument innovations users found most useful had originated from other physician-users (rather than manufacturers directly).

Overall, these studies suggest that users (physicians, in the case of medical devices) have the potential to serve an important innovative role, but that partnership with a larger player is generally necessary to bring an innovation to market.

Consequently, a recent article published in Medical Care examined the extent of physicians' contributions to new medical devices by looking at information from physician-founded startup companies and comparing it to four (4) large medical device manufacturers and the premarket approval (PMA) applications they filed (Medtronic, Johnson & Johnson, Boston Scientific and Guidant). The authors chose these companies because during the period study, each company had an ongoing, committed CVC programs and they also represented 4 of the top 10 firms by sales.

The authors of the study matched the text in patent applications for the four medical device companies to the text in patent applications of 118 startup companies that received investment from the four device companies between 1978 and 2007.

In conducting this comparison, the authors found that on average, physician-founded companies account for 11% of the information in Class III PMAs, compared with 4% from non-physician-founded companies. About 6.5% of the PMAs were >30% a result of information from physician patents, whereas 39% were >10% from physician-founded companies. In addition, in about 39% of the PMAs, at least 10% of the information came from physician-founded companies, whereas only 27% of the PMAs took >10% of their information from nonphysician outside sources.

Moreover, the authors found that the four device companies were "significantly more likely to cite physician-founded companies' patents and to incorporate them into new devices."

Physician innovation is an important component of the medical device industry. The results of this study suggest that although physician-founded companies patent at almost the same rate as nonphysician-founded companies (about 16 patents per firm, on average) physician-founded companies contribute a far greater amount of information to the devices for which incumbents ultimately seek approval.

Accordingly, the authors concluded that physicians are an "important source of medical device innovation." The results suggest that "restrictions on financial relationships between providers and industry," while potentially improving patients' trust, "may result in reduced medical innovation if physicians found fewer startups or if incumbent firms reduce investments in physician-founded startups."

More importantly, as the Sunshine Act data is made public, patients will need to better understand the critical role these physicians play in creating these devices. Patients and the media will need to provide an objective and balanced analysis of payments to physicians who create these devices and receive royalties or significant payments for their inventions and patents. If we as a country want to continue seeing new and improved medical devices, it will be critical that physicians are not attacked or stigmatized for the financial rewards their hard work earns them; especially when such work is improving the care patients receive and reducing healthcare costs elsewhere.

Background

Physicians contribute systematically to the invention of technologies underlying medical devices. Previous research has shown that at least one physician is listed on about 20% of the medical device patents registered in the United States between 1990 and 1996, and these patents received more citations across a larger breadth of citing patents than non-physician patents.

In brief, an initial idea for an innovative device usually comes from a startup company; the idea will originate with a physician or engineer. The startup company builds prototypes and conducts early testing. At this point, a much larger amount of money is necessary to take the idea through prototyping and testing. Venture capital firms usually fill this role, ushering the startup through the process to develop a marketable product. About 10% of all venture capital goes to the medical device industry, a percentage exceeded only by the biotechnology and software industries.

While physician involvement is often central to the development of medical devices, some believe that physicians who stand to benefit financially from the success of a particular device may have an incentive to provide inappropriate care or to influence others to do so.

Balancing these opposing forces— innovation on the one hand and potential conflicts of interest on the other hand—requires a better understanding of the potential magnitude of the tradeoff, as well as insight into the type of relationship in which it is embedded. This is particularly true given that the Sunshine Act explicitly includes ownership and investment relationships in its reporting requirements.

Because of the potential for harm or erosion of trust between physicians and patients, the Institute of Medicine (IOM) has made several recommendations for medical institutions to follow. At a minimum, the IOM recommends disclosure of all financial conflicts of interest. The IOM also recommends that physicians with financial interests in outcome of a clinical trial should not participate in that clinical trial.

Study and Method

The relationship between product market innovation and underlying technological inventions in therapeutic devices is difficult to examine, since medical devices are usually the product of several (and sometimes hundreds of) different patents. Moreover, physicians contribute throughout the innovation process, from patents to commercially viable products that receive PMA from FDA.

Importantly, a major aspect of innovation in this industry is that medical devices draw on a large number of patents, some of which make a large contribution to the final product and some of which make a marginal contribution.

This makes it difficult to determine how much a particular inventor contributes to the final product market innovation. It will then be difficult to determine the impact of reducing a particular source of innovation on the number of new medical devices approved.

The present study addressed this problem by examining information overlap between PMAs and patents to determine which patents are important to realized product market innovations and which are marginal. The authors quantified the contribution of physicians to medical device innovation using a novel text matching algorithm to determine the extent to which each PMA for class III medical devices relied on physician-originated patents. Class III medical devices are the highest risk classification, requiring significant testing to prove safety and efficacy.

The FDA defines class III devices as "those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury." The FDA product classification database lists in this category devices such as coronary stents, replacement heart valves, and devices that test for such conditions as organ rejection in heart transplant patients. These devices must go through a lengthy development and testing process before they can receive a PMA, although the process is shorter and less formalized than the testing process used in the pharmaceutical industry.

The authors then examined whether the use of a firm's patents is affected by the presence of a financial relationship between the manufacturer and the startup firm, and whether the effect of a financial relationship is different for physician-founded and non-physician-founded firms. The data consisted of all corporate venture capital (CVC) investment by the 4 incumbent medical device makers with established CVC arms for the years 1978–2007, all of their PMAs, and the associated patents of the incumbents and startups for the years 1978–2010.

The data did not include physician-owned patents filed through academic institutions. Thus, the authors noted that because PMAs may also incorporate patents filed through academic institutions, the study's estimates of the total contribution of physician-owned patents may be a lower bound.

Overall, the regression results suggest that device manufacturers gain more from the patents of physician-founded firms than from those of non-physician-founded firms in their subsequent invention and innovation efforts. The results also suggest that investment in the physician-founded firm leads to the use of more of its patents, a pattern that does not hold for non-physician firms. Moreover, investment may be a stronger channel for subsequent invention than for incorporation into marketed products.

Discussion

The results of this study show that the relationship between large medical device companies and startups impacts patenting and product market innovation. The actual impact of legislation such as the Sunshine Act might transmit through multiple channels.

First, the results show "that direct investment by the incumbent [manufacturer] in a startup is associated with greater use of the startup's patents (although not with a greater maximum information overlap between the startup's patents and the investor's PMAs). This suggests that curtailing investment activity in physician-founded startups might restrict large device companies' access to inventions that feed into their subsequent inventive process." The results do not establish causality; however, additional research will be necessary to establish the effect of investment on physician contributions.

Second, the PMA approval process may be prohibitive for many startups to bring a device to market independently; however, some of the insights appear to reach fruition in the PMAs of the established device companies. The results suggest that physician-founded companies contribute disproportionately in this regard.

Taken together, the results may help inform an increasingly nuanced debate on the role of physicians in medical innovation and the potential for conflicts of interest. As the implementation of Sunshine legislation begins, physicians have identified greater concerns about the impact on their role in the medical innovation ecosystem. At the same time, a recent study suggests little effect of conflict of interest rules on physician prescribing behavior. Further research is needed to understand the actual impact on physician involvement in bringing new products to market and ultimately patient care.

Finally, the authors noted that their method may shed light on innovation in industries such as pharmaceutical and biotechnology industries.

 

September 17, 2013

ASCO Policy for Relationships with Companies and How European Associations Will Benefit

Over the last ten years, European conferences have exploded with increased attendance while US conferences have shriveled. One potential reason could be the restrictions that US associations are placing on abstract presenters to prevent potential conflicts of interest. There is one association that may be one to watch if we see that trend continue.

The American Society of Clinical Oncology (ASCO) released its "Policy for Relationships With Companies". The policy puts in place a ban on submitting abstracts to their meeting from authors of journal articles who have given a promotional talk in the last two years for the supporting company, were employed by that company, or have ownership or significant investment interest.

The policy describes ASCO's comprehensive approach to addressing financial relationships held by ASCO, its key leaders and volunteers, and anyone who seeks to publish or present in an ASCO forum. However, as we will illustrate, the new policy can be overly restrictive, which may diminish the policy's usefulness.

Some highlighted parts of the policy:

DISCLOSURE OF FINANCIAL RELATIONSHIPS

A. Institutional Relationships

The ASCO and Conquer Cancer Foundation (CCF) publicly disclose external support of programmatic activities, including charitable contributions, educational grants, and sponsorships. In addition, the ASCO and CCF publicly disclose financial relationships with Companies held by their directors and officers and by the editors of the Journal of Clinical Oncology (JCO) and the Journal of Oncology Practice (JOP).

B. Individual Relationships

Many volunteers and other individuals take part in the planning, authorship, peer review, or presentation of programs or content through ASCO channels. ASCO considers it important to understand individuals' financial relationships with Companies and to make relevant information available to colleagues, learners, readers, and other affected parties. This Policy requires disclosure of certain financial and other relationships held by all individuals who:

1. are ASCO directors, officers, or senior staff;

2. serve on ASCO committees, task forces, clinical practice guideline panels, and the like, as spokespersons, or in any other volunteer activity or official capacity for ASCO;

3. submit abstracts or make presentations in ASCO educational or scientific programs;

4. submit manuscripts to JCO, JOP, and other ASCO publications;

5. have other roles for which disclosure is required by ASCO; or

6. are immediate family members of individuals who hold relationships 1 through 5 described here.

C. Information to Be Disclosed

Disclosure under this Policy generally includes but may not be limited to the following financial relationships: compensation received for employment, leadership positions, consulting activities, speaking engagements, and expert testimony; as well as ownership interests, research funding (to the individual or the institution), and licensing fees and royalties associated with intellectual property interests.

RESTRICTIONS ON CERTAIN RELATIONSHIPS

A. Original Research in ASCO Educational or Scientific Programs

Abstracts and articles concerning original research are not eligible for inclusion in an ASCO educational or scientific program if the first, last, or corresponding author has:

Participated in a speakers' bureau (on any subject) on behalf of the Company sponsor of that original research at any time during the 2 years before submission of the abstract;

 Held an employment relationship with the Company sponsorof that original research at any time during the 2 years before submission of the abstract; or

 Held a significant ownership interest in the Company sponsor of that original research at any time during the 2 years before submission of the abstract.

B. Original Research in ASCO Journals

Manuscripts (including articles and abstracts) concerning original research are not eligible for publication in JCO or JOP if the first, last, or corresponding author has:

Participated in a speakers' bureau (on any subject) on behalf of the Company sponsor of that research at any time during the 2 years before submission of the manuscript;

Held an employment relationship with the Company sponsor of that research at any time during the 2 years before submission of the manuscript; or

Held a significant ownership interest in the Company sponsor of that research at any time during the 2 years before submission of the manuscript.

The policy was released on April 22, 2013 and effective on that date. To our knowledge no prior notification was sent to ASCO members.

DISCUSSION

This policy eliminates all investors, anyone who has participated in a speaker's bureau, or any company employee(s) from submitting original research at ASCO. This will eliminate a significant number of quality abstracts based. These limits are burdensome and discriminate against many well qualified people who would otherwise be eager to submit their research to ASCO.

The draconian rules will only hurt the transfer of scientific knowledge and their benefits for the public health. Researchers want to publish, just like any other scientist, and all researchers have biases that can impact their methods. This policy implies that somehow company supported research and scientists are not quite as honest as their academic counterparts.

Fortunately there are many additional outlets for presenting and publications at the disposal of oncology researchers. In the future many of these scientists will submit their abstracts and posters elsewhere.

One can expect a significant drop in the quality of abstracts and the number of attendees at ASCO conferences. We are now in a global scientific economy--European and smaller societies are much more open to company science. American associations who have adopted similar policies have seen 30 – 40% reductions in attendance for US meetings where their European counterparts have exploded with corresponding increases in attendance.

The concern for US patients is that science presented and published in Europe can take years before US physicians know about their results. For cancer patients this is a real concern in that they may miss out on breakthroughs in treatment simply because their oncologist is "unaware" of the science.

We will see if in ten years one reminisces, "I remember ASCO when….

August 27, 2013

Continuing Medical Education: JAMA Opinion Article on CME Bias - Calls for Searching Out Illusionary Bias

In the seventies among the puritanical religious community, it was vogue to play rock
albums backwards looking for subliminal messages.   Some people even made careers out of exposing what they considered the hidden messages in records. Today we are seeing similar puritanical hysterics called for in accredited CME.  Today’s puritans using the guise of opinion papers in prestigious medical journals are calling for physicians to closely look for unapparent bias in CME programs, claiming they are not looking closely enough or perhaps not playing the recordings backwards.

Continuing medical education (CME) is required for physician relicensing, credentialing, and recertification, and physicians often depend on CME to learn about new tests and therapies. Pharmaceutical or medical device manufacturers support some CME programs, which has caused concern to some about the potential for bias and conflicts of interest.

While critics have been quiet over the past few years, a recent opinion article published in the Journal of the American Medical Association (JAMA) makes the conclusion that because "bias in CME can ultimately harm patients, … CME programs should adopt stronger measures to identify and eliminate bias, in addition to policies regarding conflicts of interest." When we received the email on the article it read "JAMA Online First" we assumed it must be an important research paper, but it was not.

The article is written by industry-critic Bernard Lo, MD, who now works at The Greenwall Foundation, which recently started a "bioethics program." The paper also received funding and support from the Greenwall Foundation, however, the "views expressed" do "not reflect the view" of the Foundation only the authors personal biases. As background Dr. Lo was the chairman of the Institute of Medicine (IOM) committee on Conflict of Interest who's report basically called for the end of all commercial support of CME and all other physician-industry collaboration with the exception of some research.  

Our main points of rebuttal to his arguments include:


There has been marked decrease in CME courses due to retraction of commercial support 


There is no evidence to support that commercially supported CME lacks value as compared to other CME sources of funding 


Dr. Lo’s proposal to ferret out bias imposes added expense to accomplish something that will add little value to the actual education in the CME activity


Dr. Lo’s proposals are based on previous failure of large research studies to show any bias in commercially supported CME and reveal that Dr. Lo conflates acceptable bias based on facts with unacceptable bias based purely on opinion.

    The article provides no balance or attempt at empirical evidence to support its assertions ignoring important characteristics of accredited CME—such as the Accreditation Council for Continuing Medical Education's (ACCME) accreditation criteria and Standards for Commercial Support—many of which contradict what the authors try to prove.

For example, there is no known evidence that commercially supported CME programs—with or without the author's so-called "bias"—have directly or indirectly caused patient harm. Further, there is no known evidence that commercially supported CME programs have led to inappropriate prescribing or treatments or medically unnecessary procedures.

To the contrary, we have cited numerous CME programs, including several that have received commercial support, which show that CME has improved patient outcomes in areas such as multiple sclerosis, hypertension, COPD, ICU patients, improved taking of family history by physician assistants, Sepsis, healthcare-associated infections, reduction in CT scans, and several other areas. More recently, accredited CME was shown to reduce healthcare costs.

The authors ignore the firewalls and rules, standards and oversight that have been in place for several years to prevent the alleged bias the authors claim. For example, in 2012, 15% of nationally accredited CME providers were placed on probation and another 30% were required to submit progress reports, demonstrating the ACCME's clear commitment to compliance. Below is a further summary of Lo's article and counterarguments to his paper.

Funding: Is There Bias in Commercially Supported CME?

Despite significant declines in commercially supported CME and the increase of "other source" income, Lo attempts to paint a picture that CME is biased by pointing out that in 2011, "75% of accredited CME providers received support from commercial entities." Yet, Lo fails to give the entire picture of commercial support.

As we noted earlier in August, commercial support for CME in 2012 decreased by 10.3% ($77,659,472) from 2011; marking the sixth year of decline. Commercial support now represents 27.3% of the total CME funding, down from 46% of total funding in 2007.

Additionally, in 2012, "income from other sources" made up 59% of total income, an increase of 6% from 2011. Income from other sources represents income other than commercial support and advertising and exhibits income. Examples of income from other sources include participant registration fees, and allocations from a provider's parent organization or other internal departments.

While 75% of CME providers may have received commercial support in 2011, Lo fails to explain that 80% of CME providers received $1 million or less in commercial support, with almost half (48%) bringing in $100,000 or less—including 25% of providers bringing in no commercial support.

In 2012, 51% of CME providers received $100,000 or less, including ~27% receiving no commercial support. Moreover, the percentage of CME providers receiving over $100,000 in commercial support decreased in 2012 from 2011—with only 17.5% of providers receiving $1-10$ million and only 1.3% of providers receiving greater than $10 million.

A large portion of nationally accredited CME providers (30.4%) received only $100,000 to $1 million in commercial support—typically enough for a few programs depending on the nature of the CME program. Lo fails to acknowledge these numbers, despite using the same data from the ACCME Annual Report.

Moreover, while Lo believes CME programs receiving commercial support may be "biased," he fails to acknowledge that the majority of CME activities (82%) did not receive commercial support in 2012, accounting for approximately 81% of physician participants and 78% of non-physician participants.

Thus, only 18% of CME activities received commercial support, and of these activities, only 19% of physician and 22% of non-physician participated. These percentages have remained stable since 2010, the first year the ACCME presented data about commercial support at the activity level.

Consequently, although commercial support of CME, the number of activities receiving such support, and the number of physician and non-physicians partaking in such activities have decreased dramatically, the article asserts that commercial support of CME raises concerns about conflicts of interest (COIs) and bias.

We have written extensively about several large studies showing undiscernible bias in commercially supported CME (Cleveland Clinic; Medscape, and UCSF).  Lo only acknowledges one of these studies—the Medscape study by Ellison. Furthermore, we have cited several surveys demonstrating that physicians find value in industry supported CME.

Nevertheless, Lo expresses concern because to date, "CME oversight has focused more on disclosing and managing COIs, particularly financial relationships between industry (such as drug companies) and CME sponsors or physicians, than on reducing bias during CME presentations." This may be a literary sleight of hand or perhaps an oversight by Dr. Lo. The ACCME standards for commercial support state "The provider must have implemented a mechanism to identify and resolve all conflicts of interest prior to the education activity being delivered to learners". Nowhere does the ACCME mention managing COI's.

Bias and COIs

Dr. Lo creates and uses his own definition of COI: "situations that present an unacceptable risk [or probability] of undue influence or bias." Contrary to his interpretation, the ACCME acknowledges a COI when circumstances allow "an individual an opportunity to affect CME content about products or services of a commercial interest with which he/she has a financial relationship." Financial relationships create actual COIs in CME "when individuals have both a financial relationship with a commercial interest and the opportunity to affect the content of CME about the products or services of that commercial interest."

Dr. Lo explains that "undue influence occurs when a CME course or presentation is inappropriately influenced by financial or personal considerations." As an example of undue influence, Lo notes that if a commercial interest (e.g., drug company) "were permitted to suggest or choose speakers, they would likely select physicians who favor their products." In fact, Lo maintains that even if such a speaker gave an unbiased presentation, "the undue influence in their selection undermines the independence of medical education and public trust in the educational process."

Unfortunately, it is unclear why Dr. Lo used this example when he acknowledges that, "commercial supporters may no longer suggest or select speakers and topics." Including this example attempts to portray a practice that has been extinct for almost a decade and the comprehensive ACCME Standards for Commercial Support (SCS) (1.1., 3.2, 5.1 and 5.2) prevent such selection from ever happening. Moreover, the Centers for Medicare & Medicaid Services (CMS) recognized the value of the ACCME SCS in its final rule implementing the Sunshine Act by exempting payments to speakers at ACCME-accredited programs where the commercial interest has no role in the content or selection of speakers as the SCS already require.

Furthermore, Dr. Lo understates what "undue influence" truly means. Courts of law have long recognized that showing "undue influence" is no easy task. To sustain a claim of undue influence, one must show coercive interference with a person's will of such severity that it causes him to do what he would not otherwise have done, or if not by coercion, then the use of other means that subverts the will causing a choice or judgment that would not otherwise have been made.  Proving such undue influence in the context of commercially supported CME is likely impossible and does a disservice to the necessary and constitutionally protected scientific exchange that is the hallmark of accredited-CME.

First, a CME program or speaker would need to be biased to such an extent that a physician would be deceived. The ACCME SCS and federal oversight makes this highly unlikely. Second, even if the program slipped through the cracks and was "biased," a physician learner would have to be coerced in some way—either by the speaker, content, or materials—to ignore the decades of training and experience the physician has to wholeheartedly and without question, subvert to the bias of the CME program. Other than hypnotism or subliminal messages, physicians are not likely to make a clinical decision based solely on a CME program without first validating the information and data first, particularly when COI's and commercial support have been disclosed.

Nevertheless, Dr. Lo believes that "bias in CME is more troubling" because it involves "presenting information, drawing conclusions, or making recommendations that are not scientifically valid or not supported by the weight of rigorous evidence." He notes that many COIs "do not result in bias," and that bias may result from "factors other than financial relationships with industry, including intellectual commitment to a therapeutic approach, limited expertise about the topic, methodological shortcomings, and poor judgment."

Dr. Lo expresses his concern with bias because while disclosure of COIs is an "essential first step in addressing them," he believes this mechanism is "counterproductive" because speakers or faculty may give "more biased advice after making a disclosure, knowing that listeners have been put on guard and may discount the advice." Yet the only support he offers for this assertion is a study regarding disclosure of industry funding in a "hypothetical" clinical trial.

The study, published in the New England Journal of Medicine (NEJM), found that industry sponsorship negatively influences physician's perception of methodologic quality and reduced their willingness to believe and act on trial findings, independently of the trial's quality. Such a comparison is problematic because it compares apples and oranges; disclosure of industry support in CME is vastly different from clinical trials in several ways.

First, clinical trial data typically focuses only on the drug being tested. Thus, industry support of such trial has a greater likelihood of distrust given the clear financial interest present. In CME programs, ACCME SCS 5.1 requires that the content or format of a CME activity or its related materials "must promote improvements or quality in healthcare and not a specific proprietary business interest of a commercial interest." Thus, when a CME provider and its faculty or speaker make a disclosure, this standard prevents any level of bias about the commercial interest from being made.

Further, in addition to the ACCME ensuring through its oversight that a CME program does not promote a commercial interest, the FDA, DOJ, and HHS-OIG all have oversight of any CME program that might cross the line from accredited-CME into product promotion. CME providers typically don't allow "more biased advice after disclosure" because it would risk jeopardizing their accreditation status and bring legal scrutiny.

Second, clinical trial data does not necessarily need to give other information about similar drugs. Conversely, ACCME SCS 5.2 requires that presentations give "a balanced view of therapeutic options," which may include the use of "generic names" and "trade names from several companies" where available. Thus again, CME providers and programs are prevented from introducing bias even after disclosure because a balanced presentation is required.

Finally, clinical trial data presents typically information on one trial. Physicians rarely attend a CME program just to learn about one clinical trial. Consequently, CME programs present many of the latest clinical data as well as relevant and recent scientific papers, updates from NIH, FDA, other federal health agencies, and other healthcare stakeholders. CME providers and their subject matter experts aggregate thousands of pages of the latest information and data and are engaged in constant and rigorous academic scholarship to ensure that CME programs include not only the latest and most up-to-date information, but a tremendous breadth of such information.

Additionally, while Dr. Lo recognizes that COI disclosure is important because it allows CME directors and learners to assess and manage COIs and potential bias, he fails to acknowledge the vast depth of the mechanisms and firewalls in place CME providers use. For example, ACCME SCS 1.1 clearly explains that a CME provider must ensure that all decisions are "made free of the control of a commercial interest," including (a) Identification of CME needs; (b) Determination of educational objectives; (c) Selection and presentation of content; (d) Selection of all persons and organizations that will be in a position to control the content of the CME; (e) Selection of educational methods; (f) Evaluation of the activity.

Accreditation Criterion 7-10 also require CME providers to develop activities/educational interventions independent of commercial interests; appropriately manage commercial support, respectively; maintain a separation of promotion from education; and actively promotes improvements in health care and NOT proprietary interests of a commercial interest.

In addition, ACCME SCS 3.2 clearly explains that a CME provider "cannot be required by a commercial interest to accept advice or services concerning teachers, authors, or participants or other education matters, including content, from a commercial interest as conditions of contributing funds or services."

Managing COIs and Bias

Despite these clear differences, and ignoring the weight of evidence demonstrating non-significant bias in commercially supported CME (as noted in the three studies above), Dr. Lo believes that physicians who attend commercially supported CME programs "probably underestimate bias" for four (4) reasons.

First, Dr. Lo maintains that physician "learners typically have insufficient knowledge about the topic to assess whether presentations are biased." This statement is entirely incorrect.

Physicians go through almost a decade or more of training and education, which teaches them to question and challenge every scientific or medical piece of evidence until they have the best answer(s) applicable to the patient or case at hand. Included in this training process is teaching physicians how to weigh evidence and potential bias in all shapes and forms. Determining whether bias is present in a CME presentation is no different. Commercial support of CME has been around almost as long as CME and physicians are well aware of the disclosures being made and how to assess the information being presented.

Moreover, the fact that complaints are submitted to the ACCME, individual CME providers, and the FDA all demonstrate physicians have sufficient knowledge to assess bias in CME presentations. If more bias was present, we would expect to see more accredited CME providers on probation, losing their accreditation status, or receiving letters from law enforcement. However, we are unaware of any pervasive existence of such events. Consequently, Lo may believe that the absence of such complaints and actions suggests that physicians have insufficient knowledge to report the bias. Yet, as the three studies above have already demonstrated, the minimal complaints and regulatory actions is a product of a well functioned CME accreditation system that prevents and significantly reduces any potential COIs and bias.

Second, Dr. Lo believes that learners have little incentive to give detailed, thoughtful comments. This statement is untrue and unsupported by any evidence. Those who works in the CME industry or for a CME provider would be able to tell Dr. Lo about the dozens of verbal and written comments or post-activity surveys CME providers receive on a range of topics, including bias. In fact, contrary to Lo's unfounded assertion, physicians have strong incentives to give detailed and thoughtful comments because they understand that doing so will lead to improved CME programs, assistance in helping CME providers produce outcomes measures, and are often required to earn the full CME credit.

Third, Dr. Lo asserts that questionnaires to detect bias in CME commonly pose only one general question about bias, ask for global, intuitive judgments, and do not define key terms operationally. Typical items are "The data presented in the program were incomplete or framed in a biased fashion" and "The data were presented in an unbalanced manner (italics added)." Respondents to such generally worded items identify bias through implicit "we know it when we see it" judgments—a standard that has been widely criticized. Dr. Lo cites one study, which suggests that asking CME learners to check off specific manifestations of bias leads to a higher rate of reporting. In other words, learners may need to be told what to look for in order to see it. This method has been proven in polling to produce its own set of "biases" and often leading questions are just that "leading".

Finally, Dr. Lo argues that even when questions did ask about specific manifestations of bias, they addressed only the simplest forms of bias, such as showing a company logo on slides or mentioning trade names.

The last two assertions by Lo are problematic. In essence, Lo asserts that because current measures for bias in CME are not finding any bias, the questionnaires and questions CME providers are asking must be wrong or physicians do not understand them. Dr. Lo is attempting to generate more fuel for his own scholarship by bashing an otherwise well-run accredited CME system. He cannot find evidence of any bias, fail to acknowledge the evidence showing no bias (three largest studies), and does not acknowledge the ACCME SCS.

Moreover, physicians are constantly assessing the bias of a CME program during the program itself. To suggest that a physician would need individual questions or more tailored questions to each aspect of the program to find evidence of bias amounts to a witch-hunt. Physicians need to pay attention during CME programs to the actual content and data. It is already difficult enough to get physicians to retain knowledge and improve clinical care based on CME programs. Attempting to incorporate more distractions and questions about potential bias will only further inhibit the quality of CME programs and the impact they are having. And for what purpose? To bolster Dr. Lo's own bias and his ethics career of crying "conflict" when it has been proven no evidence exists.

Consequently, Lo believes that CME providers should use "scoring systems or checklists" to better identify bias in CME, instead of using global or implicit evaluations. He asserts that CME providers should "Ask about specific manifestations of bias that can be readily and consistently identified," such as:

  1. Does the presentation compare options for managing the condition, including generic drugs and lifestyle changes? Are their advantages and disadvantages compared? Framing a presentation as "New drugs for XX" rather than "Treatment of XX in 2013" leads to bias in favor of new drugs. Even if presentations about studies of new drugs are not distorted, bias occurs if data on new drugs are not put in the context of other approaches and established therapies.

First, the ACCME SCS already require this in CME programs. As noted above, ACCME SCS 5 requires that the "content or format of a CME activity or its related materials must promote improvements or quality in healthcare and not a specific proprietary business interest of a commercial interest" and presentations "must give a balanced view of therapeutic options," including use of generics and multiple trade names.

Second, this question suggests something that the article itself did not do: acknowledge the advantages and benefits of commercial support as well as the mechanisms already present to reduce and manage bias in CME.

Additionally, this point is only relevant to a small minority of CME programs sponsored by commercial support. For instance, only certain types of diseases will have generic drugs and lifestyle changes that would make sense from an educational and evidence-based standpoint to include, such as type-one diabetes or various cancers. On the other hand, physicians treating complex and chronic diseases with debilitating side effects are seeking new information and clinical data about drugs that may be in clinical trials because their patients have no other options.

  1. Does the presentation use a critical literature review or meta-analysis to summarize the totality of evidence? A comprehensive critical review of evidence or a meta-analysis as the most rigorous way to provide context is far more preferable to speakers' opinions unsupported by evidence or by evidence-based practice guidelines from a trustworthy source.

This suggestion is problematic because many physicians attend CME programs for the specific purpose of learning about the recent developments in medicine, rather than historical overviews of older data or comparisons that may not be as relevant. More importantly, many treatments that may be discussed at CME programs regarding cutting edge treatments are small phase II or emerging phase III trials that are saving lives. How can a CME provider do a meta-analysis for such treatments?

  1. Are the limitations of data for new therapies discussed? Evidence from pivotal clinical trials is often limited in many ways—insufficient power to detect important but rare adverse effects and drug interactions; exclusion of patients with advanced age, poor functional status, and comorbidities; and lack of long-term outcomes and postmarketing safety data. Furthermore, adherence to medications in real-world settings may be lower than adherence in clinical trials with research staff. Thus, the results of pivotal trials may not hold for patients commonly observed in clinical practice. Presentations on new drugs should discuss these limitations and compare the findings for new drugs to the much more extensive data regarding established therapies.

As already noted, ACCME SCS 5 requires that CME presentations "give a balanced view of therapeutic options." In addition, many CME providers have begun using case studies and other interactive patient programs in faculty and speakers are able to share their experience with treatments based off of drug interactions, age, and other factors noted above. However, these new approaches can be expensive, which demonstrates continued need for commercial support to off-set the costs to physicians.

 

  1. What important pertinent topics are missing from the presentation or course? Certain topics, such as patient-physician communication, counseling, and quality improvement, are infrequently covered in industry-supported CME, although these topics represent common and important challenges in clinical practice.

Given the strict time limitations and already dwindling resources, it is likely difficult for many CME providers to incorporate more topics into accredited CME programs, particularly those discussing new clinical data and treatments. It would almost be impossible for a CME program to include all of the content to meet the educational objectives of the CME program and to achieve educational outcomes on such objectives while also addressing issues such as communication or counseling. While such issues are certainly important, the value of CME to physicians is by interacting with experts and learning about recent changes in the management and treatment of a particular treatment.

Dr. Lo recommends that physicians who are knowledgeable about the topic should review slide decks before presentations using these "checklists." He notes that reviews should be knowledgeable about evidence-based medicine and should have no promotional relationships with relevant companies. This expertise is needed to assess whether presentations lack balance or omit important information or issues.

Dr. Lo misunderstands that most nationally accredited CME providers already do this, not only to comply with ACCME accreditation and SCS standards, but also to ensure the highest quality education and training. We do agree with Lo's suggestion that peer reviewers be rewarded through offering CME credits, as some medical journals do for peer reviewers, and including such reviews in promotions and tenure packets.

Ultimately, Dr. Lo concludes that the ACCME should "conduct periodic reviews of how CME programs identify and respond to bias and, in the spirit of quality improvement, disseminate best practices and deidentified reviews to other CME programs." This recommendation, as we have noted through this article, may not be necessary given the significant oversight ACCME already practices and the level of compliance CME providers engage in with respect to commercial support.

We agree with Dr. Lo "Bias is presenting information, drawing conclusions, or making recommendations that are not scientifically valid or not supported by the weight of rigorous evidence." Without any evidence of bias in CME or patient harm, Lo's attack on commercially supported CME, is a self-serving article that is unbalanced and biased. So Dr. Lo where is your rigorous evidence in lashing out at ethical CME providers. Dr. Lo's bias and unbalanced discussion are impossible to miss. Dr. Lo has turned his "bias" into "ethics" that is quite a slight of hand.

Next time you attend a CME program, perhaps the critics can record it and play it backwards, who knows they may find hidden messages such as "prescribe more ….." or use …." Or perhaps take the faculty at their word for being honest physicians committing significant personal time in helping physicians understand ever more complex medicine.

For the record, I have my own set of biases, I believe that commercial support of CME is good for society, CME providers have invested heavily in insuring fair balance and resolving conflicts of interest that may exist. The practice of CME has made my life better and the life of countess friends of mine who would have died prematurely without the collaboration that currently exists to improve our health.

Many thanks to the doctors with the Association of Clinical Researchers and Educators who gave us many more arguments than we were able to use in writing this article. The bottom line is they all thought Dr. Lo's original article was pure "rubbish."

 "There are no conflicts of interest among rational men in a free society."  Ayn Rand.



July 17, 2013

JAMA Drops Requirement for Independent Statistical Analysis for Industry Funded Trials

The Journal of American Medical Association dropped its requirement for independent statistical analyses of industry-funded clinical trials. Editor-in-Chief Howard Bauchner, MD, cited improvements in the quality of clinical-trial reporting for making the 8-year-old policy unnecessary.

 

Bauchner notes that changes in the reporting of clinical trials over the last decade have addressed threats to the validity of research. "In addition, more widespread availability and detailed review of trial protocols and statistical analytic plans has helped clarify the intention of investigators at the time studies are designed, and along with gradual increases in the amount of data sharing, have facilitated the ability of reviewers and journal editors to assess the scientific validity of studies," said Bauchner.

 

In 2005, The Journal of American Medical Association adopted policies addressing: "conflicts of interest, financial aspects of research, and the role of sponsors in funded research." The policies required that an academic biostatistician conduct independent statistical analysis for industry-sponsored and industry-analyzed studies. The policy was created in response to several high-profile trials that had problems with: "data integrity, inappropriately conducted statistical analysis, and incomplete reporting of major findings."

 

Some in academia and industry viewed the policy as a barrier to the publication of trial results. In addition, Bauchner notes over the past two years, the Journal has found: "the conduct of additional analyses by independent academic biostatisticians generally did not result in meaningful changes in the study results."

 

Bauchner cites: "Advances over the past decade in standards of clinical trial reporting, enhanced understanding of the threats to validity of clinical research, increasing data transparency, and our experience support the change in policy." Now, the Journal: "will evaluate and consider for publication clinical trials that are analyzed by statisticians employed by or contracted by the study sponsor, without requiring independent statistical analysis by an academic biostatistician."

 

The Journal will continue other requirements, including the submission of a copy of the trial protocol and statistical analytic plan with amendments, and trials must be registered with an approved publicly accessible database. Changes to the protocol, analysis plan, or trial registration that occur after the beginning of the trial must be explained in detail and justified with appropriate documentation. Further, if Journal editorial reviews raise concerns: "we reserve the right to request the entire data set from authors to conduct our own statistical analysis," said Bauchner.

 

The Journal stands by its previous editorial stating a preference that investigators from academic institutions, as opposed to employees from the study's sponsor, prepare the manuscripts and analyze data from clinical trials. Bauchner stressed: "As with all manuscripts, the first priority in decisions about publication will always be the integrity of the research."

 

This change in standards verifies that company sponsored science is very high quality and that the additional requirement was unnecessary. When JAMA embarked on this additional requirement they had expected other journals to fall in line, but that did not happen.

 

Negative statements like the original requirement against industry sponsored trials has caused physicians to discredit industries trials and patients have suffered because of this. It is a pity that the JAMA retains the prejudice that studies written and analyzed by academia are by their nature superior to studies written and analyzed by industry. These religious believes run counter to science but at least they were honest enough to admit when they were wrong.

 

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