In the JournalsPerspective

Increased Conflict of Interest Policies Needed for Guideline Committees, Advocacy Organizations

The guideline for cholesterol by the American College of Cardiology and American Heart Association, as well as the guideline for hepatitis C virus treatment by the American Association for the Study of Liver Diseases and Infectious Diseases Society of America did not fully meet the Institute of Medicine standards for commercial conflict of interest management, according to studies published in JAMA Internal Medicine. The authors noted that modest or substantial industry support was common among many patient advocacy organizations, and that such support could influence their positions.

Such findings raise concerns about the trustworthiness of clinical guidelines and independence of patient advocacy organizations (PAOs), warranting more consistent and robust conflict of interest (COI) frameworks, policies and practices, they said.

Seminal hepatitis C virus and cholesterol management guidelines

In the development of recent important clinical guidelines, little is known about whether the Institute of Medicine (IOM) standards for managing COI have been adhered to, Akilah A. Jefferson, MD, MSc, from the department of bioethics at NIH, and Steven D. Pearson, MD, MSc, from the Institute for Clinical and Economic Review, wrote.

The researchers evaluated this issue in the development and publication of two recent guidelines: the 2013 American College of Cardiology and American Heart Association cholesterol management guideline and the 2014 American Association for the Study of Liver Diseases and Infectious Diseases Society of America hepatitis C virus (HCV) management guideline. They evaluated each guideline for adherence to the IOM standards for commercial COI published in the 2011 special report Clinical Practice Guidelines We Can Trust — which call for no commercial COI among guideline committee chairs and cochairs and for less than half of committee members to have commercial COI — and other IOM standards for guideline development and evidence review.

The cholesterol guideline committee consisted of 16 members, of whom seven (44%) reported commercial COI, with all disclosing industry-sponsored research and six (38%) disclosing consultancy in addition. One out of three guideline chairs and cochairs (33%) also disclosed commercial COI.

The HCV guideline committee consisted of 29 members, of whom 21 (72%) disclosed commercial COI, with 18 (62%) reporting industry-sponsored research, 10 (34%) serving on advisory boards, five (17%) serving on data safety monitoring boards, three (10%) acting as consultants and three (10%) reporting other honoraria. In addition, four out of six guideline cochairs (67%) reported commercial COI, with all four reporting additional COI in other publications that were not listed in their guideline disclosures.

Contemporaneous literature reviews for both the cholesterol and HCV guidelines identified additional commercial COIs.

While the HCV guideline met all 9 IOM guideline development and evidence standards, the cholesterol guideline only met 5 (56%).

These results indicate that even 5 years after the publication of the IOM standards, management levels of commercial COI remain an important issue, according to Jefferson and Pearson.

“We believe that our study highlights the need for broader and more explicit adoption of the IOM’s framework for COI management and a commitment from specialty societies to adhere to the IOM standards,” they concluded. “Adoption of consistent COI frameworks will help ensure that the clinical guidelines establishing appropriate care in the United States are developed in a way that can merit the trust of patients, clinicians, and the broader public.”

In a statement, Richard Chazal, MD, FACC, president of ACC, defended the ACC’s approach to developing guidelines.

“The American College of Cardiology is committed to ensuring balance, independence, objectivity, and scientific rigor in all of its activities,” he said. “The policies adopted by the writing panel of the 2013 cholesterol guideline to manage authors’ relations with industry were in effect when this effort began under NHLBI in 2008 until the process was transferred to ACC/AHA in 2013.  In the interest of transparency, the ACC/AHA requested that panel authors resubmit RWI disclosures as of July 2013. These policies are outlined in the methods section of the guideline. All relationships relevant to these guidelines are also disclosed in Appendix 1 of the report.” 

Patient advocacy organizations

PAOs, such as the American Cancer Society and the American Heart Association, are influential health care stakeholders, according to Susannah L. Rose, PhD, of the department of bioethics at Cleveland Clinic, and colleagues.

“Many PAOs report having financial relationships with for-profit industry, yet little is known about the nature of these relationships,” they wrote.

To address this issue, Rose and colleagues distributed a survey to a nationally representative random sample of 439 PAO leaders, representing 5.6% of 7,865 PAOs in the U.S., from Sept. 1, 2013, to Jun. 30, 2014. The researchers identified PAO leaders from the leadership contact information section on organizational websites, verifying by phone when necessary. They also used GuideStar and LexisNexis if such contact information was not available. The organizational leaders were asked about the nature of their activities, their financial relationships with industry and the perceived effectiveness of their COI policies.

Approximately 66% of PAO leaders (n = 289) returned their survey with at least 80% completion. There was a wide variation in size, funding, activities and disease focus among PAOs.

Results indicated that 67% of PAO leaders (virtually all non-profit) reported receiving funding from for-profit organizations. In addition, 12% reported receiving more than half of their funding from industry. A median of 45% of industry support was from pharmaceutical, device and/or biotechnology sectors. Most respondents (81.8%) reported that COIs were very or moderately relevant to their respective PAO. Slightly more than half (55%) of PAO leaders believed that their organization had very good COI policies in place. Approximately 8% reported feeling pressure to conform their positions to the interest of corporate donors.

“Financial relationships between PAOs and industry demand effective steps to ensure that these groups serve their constituents’ interests while minimizing risks of undue influence and bias,” Rose and colleagues concluded. “Given the growing ability of PAOs to influence health care policy and practice, their financial practices and safeguards demand the same degree of scrutiny applied to other key actors in the health care landscape.” – by Alaina Tedesco

Disclosures: Jefferson and Pearson reported receiving support from the National Institutes of Health. Pearson also reported receiving research grants during the past 2 years from the Blue Shield of California Foundation, the California Health Care Foundation, the Laura and John Arnold Foundation, and the National Pharmaceutical Council and reported membership dues paid to the Institute for Clinical and Economic Review during the past 2 years from Aetna, America’s Health Insurance Plans, Anthem, Blue Shield of California, CVS Caremark, Express Scripts, Harvard Pilgrim Health Care, OmedaRx, United Healthcare, Kaiser Permanente, Premera Blue Cross, Prime Therapeutics, Health Care Service Corporation, AstraZeneca, Genentech, GlaxoSmithKline, Johnson & Johnson, Merck, the National Pharmaceutical Council, Takeda Pharmaceuticals, Pfizer, Novartis, and Eli Lilly and Company. Rose and colleagues reported funding from Edmond J. Safra Center for Ethics at Harvard University.

The guideline for cholesterol by the American College of Cardiology and American Heart Association, as well as the guideline for hepatitis C virus treatment by the American Association for the Study of Liver Diseases and Infectious Diseases Society of America did not fully meet the Institute of Medicine standards for commercial conflict of interest management, according to studies published in JAMA Internal Medicine. The authors noted that modest or substantial industry support was common among many patient advocacy organizations, and that such support could influence their positions.

Such findings raise concerns about the trustworthiness of clinical guidelines and independence of patient advocacy organizations (PAOs), warranting more consistent and robust conflict of interest (COI) frameworks, policies and practices, they said.

Seminal hepatitis C virus and cholesterol management guidelines

In the development of recent important clinical guidelines, little is known about whether the Institute of Medicine (IOM) standards for managing COI have been adhered to, Akilah A. Jefferson, MD, MSc, from the department of bioethics at NIH, and Steven D. Pearson, MD, MSc, from the Institute for Clinical and Economic Review, wrote.

The researchers evaluated this issue in the development and publication of two recent guidelines: the 2013 American College of Cardiology and American Heart Association cholesterol management guideline and the 2014 American Association for the Study of Liver Diseases and Infectious Diseases Society of America hepatitis C virus (HCV) management guideline. They evaluated each guideline for adherence to the IOM standards for commercial COI published in the 2011 special report Clinical Practice Guidelines We Can Trust — which call for no commercial COI among guideline committee chairs and cochairs and for less than half of committee members to have commercial COI — and other IOM standards for guideline development and evidence review.

The cholesterol guideline committee consisted of 16 members, of whom seven (44%) reported commercial COI, with all disclosing industry-sponsored research and six (38%) disclosing consultancy in addition. One out of three guideline chairs and cochairs (33%) also disclosed commercial COI.

The HCV guideline committee consisted of 29 members, of whom 21 (72%) disclosed commercial COI, with 18 (62%) reporting industry-sponsored research, 10 (34%) serving on advisory boards, five (17%) serving on data safety monitoring boards, three (10%) acting as consultants and three (10%) reporting other honoraria. In addition, four out of six guideline cochairs (67%) reported commercial COI, with all four reporting additional COI in other publications that were not listed in their guideline disclosures.

Contemporaneous literature reviews for both the cholesterol and HCV guidelines identified additional commercial COIs.

While the HCV guideline met all 9 IOM guideline development and evidence standards, the cholesterol guideline only met 5 (56%).

These results indicate that even 5 years after the publication of the IOM standards, management levels of commercial COI remain an important issue, according to Jefferson and Pearson.

“We believe that our study highlights the need for broader and more explicit adoption of the IOM’s framework for COI management and a commitment from specialty societies to adhere to the IOM standards,” they concluded. “Adoption of consistent COI frameworks will help ensure that the clinical guidelines establishing appropriate care in the United States are developed in a way that can merit the trust of patients, clinicians, and the broader public.”

In a statement, Richard Chazal, MD, FACC, president of ACC, defended the ACC’s approach to developing guidelines.

“The American College of Cardiology is committed to ensuring balance, independence, objectivity, and scientific rigor in all of its activities,” he said. “The policies adopted by the writing panel of the 2013 cholesterol guideline to manage authors’ relations with industry were in effect when this effort began under NHLBI in 2008 until the process was transferred to ACC/AHA in 2013.  In the interest of transparency, the ACC/AHA requested that panel authors resubmit RWI disclosures as of July 2013. These policies are outlined in the methods section of the guideline. All relationships relevant to these guidelines are also disclosed in Appendix 1 of the report.” 

Patient advocacy organizations

PAOs, such as the American Cancer Society and the American Heart Association, are influential health care stakeholders, according to Susannah L. Rose, PhD, of the department of bioethics at Cleveland Clinic, and colleagues.

“Many PAOs report having financial relationships with for-profit industry, yet little is known about the nature of these relationships,” they wrote.

To address this issue, Rose and colleagues distributed a survey to a nationally representative random sample of 439 PAO leaders, representing 5.6% of 7,865 PAOs in the U.S., from Sept. 1, 2013, to Jun. 30, 2014. The researchers identified PAO leaders from the leadership contact information section on organizational websites, verifying by phone when necessary. They also used GuideStar and LexisNexis if such contact information was not available. The organizational leaders were asked about the nature of their activities, their financial relationships with industry and the perceived effectiveness of their COI policies.

Approximately 66% of PAO leaders (n = 289) returned their survey with at least 80% completion. There was a wide variation in size, funding, activities and disease focus among PAOs.

Results indicated that 67% of PAO leaders (virtually all non-profit) reported receiving funding from for-profit organizations. In addition, 12% reported receiving more than half of their funding from industry. A median of 45% of industry support was from pharmaceutical, device and/or biotechnology sectors. Most respondents (81.8%) reported that COIs were very or moderately relevant to their respective PAO. Slightly more than half (55%) of PAO leaders believed that their organization had very good COI policies in place. Approximately 8% reported feeling pressure to conform their positions to the interest of corporate donors.

“Financial relationships between PAOs and industry demand effective steps to ensure that these groups serve their constituents’ interests while minimizing risks of undue influence and bias,” Rose and colleagues concluded. “Given the growing ability of PAOs to influence health care policy and practice, their financial practices and safeguards demand the same degree of scrutiny applied to other key actors in the health care landscape.” – by Alaina Tedesco

Disclosures: Jefferson and Pearson reported receiving support from the National Institutes of Health. Pearson also reported receiving research grants during the past 2 years from the Blue Shield of California Foundation, the California Health Care Foundation, the Laura and John Arnold Foundation, and the National Pharmaceutical Council and reported membership dues paid to the Institute for Clinical and Economic Review during the past 2 years from Aetna, America’s Health Insurance Plans, Anthem, Blue Shield of California, CVS Caremark, Express Scripts, Harvard Pilgrim Health Care, OmedaRx, United Healthcare, Kaiser Permanente, Premera Blue Cross, Prime Therapeutics, Health Care Service Corporation, AstraZeneca, Genentech, GlaxoSmithKline, Johnson & Johnson, Merck, the National Pharmaceutical Council, Takeda Pharmaceuticals, Pfizer, Novartis, and Eli Lilly and Company. Rose and colleagues reported funding from Edmond J. Safra Center for Ethics at Harvard University.

    Perspective

    During the creation of the AASLD/IDSA HCV Guidance, the governing boards of AASLD and IDSA gave careful consideration to the role of panel members with clinical research experience. It was determined that these members — whose institutions received funding rather than the researchers receiving personal funding — would bring invaluable expertise in managing the complex new direct-acting drugs that were rapidly emerging at the time the Guidance was initially drafted, and these members continue to offer unique perspective and contributions to the panel.

    The panel was established with the goal of having no personal financial conflicts of interest with companies developing HCV treatments among its chairs and among fewer than half of its panel members. Interaction with other companies not directly having agents under consideration, or in the developmental pipeline, was considered acceptable after full disclosure to the co-chairs.

    The IOM provides valuable recommendations for guideline development, and AASLD and IDSA are pleased to see the AASLD/IDSA HCV Guidance is in line with nearly all of these recommendations. The Guidance’s widespread acceptance by the medical community and its incorporation into multiple government and nongovernmental agency policies attest to its credibility, objectivity and ultimate value to patients.

    • Anna S. Lok, MD, FAASLD, president of AASLD and William G. Powderly, MD, FIDSA, president of IDSA

    Disclosures: IDSA’s funding comes from a variety of sources, including membership dues, journal royalties, Annual Meeting fees, and grants from government agencies, private foundations, and industry. AASLD also receives funding from a variety of sources, including Annual Meeting fees, membership fees and research and fellowship awards.

    Perspective

    Few issues are more important to the American Heart Association than translating scientific evidence into guidelines and performance measures for healthcare providers, a process we have been engaged in for several decades. The use of these evidence-based guidelines has been proven to achieve their purpose in improving both the quality of care and actual health outcomes for patients.

    The American Heart Association has long enforced strict policies for preventing any influence of industry, any bias in evaluating evidence, and any lack of balance in considering all the available evidence. In 2010, we refined our policies to require even more stringent management of relationships with industry, to align with the Council of Medical Specialty Societies (CMSS), and we re-evaluated them in 2011 with the publication of the Institute of Medicine’s “Clinical Practice Guidelines We Can Trust.” Our policies are available online. 

    It is important to recognize that there can be multiple forms of potential conflict of interest, and we should not assume that those without financial ties to industry might not have other conflicts. We have always felt that an important responsibility of our overall Task Force on Practice Guidelines is to select authors who have demonstrated by their track records that they are unbiased and conscientious in their evaluation of evidence. We use similar criteria in choosing the multiple peer reviewers who evaluate these documents, and finally, we engage those members of our highest scientific body with no relationships with industry or other forms of potential COI, to provide a final unbiased review and approval. Dozens of such individuals reviewed the Cholesterol Guidelines, and none suggested any commercial or other bias.

    The American Heart Association remains fully committed to transparency in the development of all our guidelines. We continue to examine our policies regarding all potential conflicts of interest, and we will continue to enhance our practices as needed in the future.

    *Editor's note: This press statement was released following a query from Healio Internal Medicine.
    • Elliott Antman, MD
    • Past president of the American Heart Association

    Disclosures: The American Heart Association/American Stroke Association receives funding primarily from individuals. Foundations and corporations donate as well, and fund specific programs and events. Strict policies are enforced to prevent these relationships from influencing the association’s science content. Financial information for the American Heart Association, including a list of contributions from pharmaceutical companies and device manufacturers, is available at www.heart.org/corporatefunding.