Rx for the pharmaceutical industry: call your doctors.
|Article Type:||Viewpoint essay|
Pharmaceutical industry (Laws, regulations and rules)
Medical ethics (Evaluation)
|Author:||Kitsis, Elizabeth A.|
|Publication:||Name: The Hastings Center Report Publisher: Hastings Center Audience: Academic; Professional Format: Magazine/Journal Subject: Biological sciences; Health Copyright: COPYRIGHT 2009 Hastings Center ISSN: 0093-0334|
|Issue:||Date: July-August, 2009 Source Volume: 39 Source Issue: 4|
|Topic:||Event Code: 240 Marketing procedures; 930 Government regulation; 940 Government regulation (cont); 980 Legal issues & crime Advertising Code: 94 Legal/Government Regulation Computer Subject: Company marketing practices; Government regulation|
|Product:||SIC Code: 2833 Medicinals and botanicals; 2834 Pharmaceutical preparations|
|Geographic:||Geographic Scope: United States Geographic Code: 1USA United States|
Pharmaceutical companies are guilty of moral misconduct. They
stretch the definitions of illnesses, such as bipolar disorder, in order
to expand markets. (1) They sponsor seeding studies, such as
Merck's ADVANTAGE trial (Assessment of Differences between Vioxx
and Naproxen to Ascertain Gastrointestinal Tolerability and
Effectiveness), in order to facilitate the rapid uptake of a new drug at
the time of its launch. (2) They promote unapproved uses of drugs, such
as Lilly's "Viva Zyprexa" campaign, in which sales
representatives recommended the drug for dementia. (3) These activities
all aim to maximize sales.
Yet drug companies have translated scientific discoveries into products that have improved and extended the lives of millions of people. For example, statins prolong survival in patients with coronary artery disease, (4) tumor necrosis factor inhibitors retard joint destruction in patients with rheumatoid arthritis, (5) and imatinib induces remission in most patients with chronic myeloid leukemia. (6) Sometimes alone and sometimes in collaboration with investigators from academia or government, the pharmaceutical industry has helped people live longer, better lives.
Drug companies are also a source of crucial research funding. The U.S. pharmaceutical industry invested $47.9 billion in research and development in 2007. (7) If the current level of productivity and investment from the private sector is to continue without repeating the pitfalls of the past, we must collaborate with industry to find better ways of ensuring ethical drug development. Multiple changes will be necessary to achieve this end. External reforms so far have come from the government, (8) academia, (9) and journal editors. (10) Internal ethics initiatives have also been introduced at several companies. (11) For example, Roche established an external Science and Ethics Advisory Group. (12) Merck and Abbott have established ethics offices. (13) GlaxoSmithKline, Lilly, Merck, and Abbott maintain confidential "helplines" that employees may call to report potential violations. (14) The industry deserves credit for taking these steps. Whether they actually have a positive impact or serve simply as window-dressing intended to disarm critics remains to be seen. What else can be done to bridge the gap between the industry's key role in producing important products and the parade of unethical actions that plague it?
As a physician and a former vice-president of Pfizer, I believe that a previously unrecognized way of addressing the problem may already exist inside the pharmaceutical industry itself, in the form of the physicians who work there. In order for industry physicians to ensure ethical behavior, it is necessary that they: 1) make decisions about ethical issues; 2) acknowledge they have a moral duty to ensure that their company behaves ethically; 3) possess the knowledge and skills required to perform their jobs; 4) have the responsibility and the incentive to conduct clinical research ethically, rather than just to increase revenue; and 5) work in a culture that recognizes and supports their expertise and their role.
Roles and Obligations of Physicians in Industry
Approximately eighty-six thousand medical and scientific professionals work in drug companies in the United States. (15) Pharmaceutical physicians are deployed throughout the industry in many positions--as bench researchers, focusing on the discovery of new drugs; as clinical researchers, designing, implementing, and overseeing phase I--IV trials; and as safety experts, focusing on "pharmacovigilance," which refers to monitoring the side effects of a drug. Others compile medical information, review promotional materials, create speakers bureaus, and review independent medical grants. Many work with marketers and other colleagues to create product development plans, launch new products, and implement strategies to support approved compounds.
Given the diversity of jobs carried out by physicians in industry, it is not surprising that they participate in making many ethically laden decisions, ranging from the selection of disease targets to the proper conduct of trials in the third world to the monitoring and management of potential safety issues. Physicians in industry are in the thick of ethical conflicts in drug development and therefore well positioned to prevent them.
Simply being in the right spot at the right time is not enough, though. Physicians in industry must realize that they have an obligation to ensure ethical conduct. Like academic clinical researchers, industry physicians must ensure the welfare of patients in their clinical trials (16) and serve truth in the name of science. (17) Like public health physicians, they have a duty to protect the health of the population as a whole. (18) However, unlike their colleagues in clinical and academic settings, pharmaceutical physicians work for companies that are motivated by a powerful organizational interest--profit. Working at the nexus of patient welfare, science, and profit--the crux of ethical conflict in drug development--these individuals wear several hats. How can they navigate their multiple and sometimes conflicting roles to ensure that patient welfare is protected and science is advanced in a profit-driven industry?
Edmund Pellegrino once proposed that academic clinical investigators try to resolve similar conflicts by turning to a set of hierarchically arranged values: patient welfare guides physicians, truth drives scientists, and self-interest steers the individual. (19) Patient welfare is considered primary and takes precedence over science, which in turn trumps self-interest. Tweaking this scheme for physicians in pharmaceutical companies would make the protection of patient and social welfare the primary consideration, followed by scientific value, followed by commercial and individual self-interest. Ethical drug development does not necessarily preclude company profit; it just assigns it appropriate moral rank.
Dissenters might argue that physicians as well as other industry employees already raise and resolve ethical concerns. After all, many drug company staff members who are not physicians--including businesspeople--are upstanding citizens who speak out when activities are questionable. Moreover, drug companies also employ large numbers of lawyers and regulatory professionals to ensure proper conduct of their work. These resources are valuable and legitimately help companies stay on track. Nevertheless, problems still arise. And although nonmedical staff may act with integrity, they do not have a professional obligation to ensure patient welfare. Physicians do.
Ensuring that physicians in industry are well educated in areas permeated by bioethics--such as drug development, clinical research, and pharmacology--makes common sense. Yet currently, although all researchers who conduct government-sponsored clinical research are required to complete a training program on human subjects research, (20) there is no such requirement for medical and scientific professionals who conduct research in the pharmaceutical industry.
An initial step toward filling this gap would be to require all physicians in industry to complete training similar to that of researchers participating in National Institutes of Health-sponsored studies. The syllabus for pharmaceutical physicians could be broadened to cover pharmaceutical ethics, including the multifaceted ethical issues that arise in the development and marketing of drugs. Eventually, all pharmaceutical company employees could complete pharmaceutical ethics training, since drug company employees with diverse roles may participate in decision-making that has ethical implications.
A second, more aggressive way to raise the ethical bar in industry would be to formalize the training of pharmaceutical physicians as a subspecialty--"pharmaceutical medicine." The specialty board movement began in the early 1900s to assure the public that physicians claiming to have specific expertise were qualified to carry out their activities. (21) Given the current low level of public trust in drug companies, requiring a key segment of their employees to complete a rigorous training program could be a welcome change.
Like other subspecialties--for example, sleep medicine or hospice and palliative medicine--the pharmaceutical medicine certification program could be jointly developed. In this case, the American Board of Internal Medicine, the American Board of Preventive Medicine, the American Board of Pediatrics, the American Board of Obstetrics and Gynecology, and the American Board of Medical Genetics could collaboratively create a program. To be eligible for certification in the subspecialty of pharmaceutical medicine, physicians could be required to be previously certified in internal medicine, complete a year of fellowship training in a pharmaceutical or biotechnology company, complete course work at an accredited university in pharmaceutical medicine, and pass a certification examination. Membership in a professional association, whose basic functions would be self-regulation and support of its members, could further bolster physicians' ability to do their jobs.
However, even if physicians in industry are trained and recognized to have special knowledge and skills to ensure ethical drug development, this potential might not always be realized. No matter how virtuous and well informed an individual may be, working in a monolithic culture is not an easy task. Indeed, rather than shaping corporate decisions, physician behavior may itself be shaped by the corporate environment.
Organizational Structure and Culture
Problems arise when a company's structure undermines the values its workers are expected to uphold. (22) While junior physicians in drug companies often report to more experienced physicians or other scientists, this is not always the case. Some pharmaceutical companies use team-based structures wherein physicians report either directly or indirectly to business executives, who may be judged primarily on the financial success of their products. Organizational structures in which medical staff report at any level to business executives can tip the scale toward the commercial interests of the corporation. Clearly, physicians should be assigned decision-making responsibility for medical activities. The involvement of marketing executives in decisions relating to protocol design or medical information provided to consumers is inappropriate, since business considerations should play no role in these activities.
Similarly, the performance evaluation system used by a company can impact the behavior of its employees. If physicians are evaluated by people who share their goals and values, whether the physicians are upholding those values might well be noted. However, if their performance is assessed by people whose primary interest is profit, there is dissonance within the ethical framework, and problems may ensue.
A company's reward system can exacerbate this problem. Rewards such as salary increases, bonuses, stock options, and promotions are typically used to reinforce certain behaviors. For industry physicians to meet their obligations to patients, science, and society, the reward system should be tied to milestones that reflect these pursuits; ethical behavior should be rewarded. If, on the other hand, rewards are tied in any way to the company's financial performance, self-interest may lead physicians to act in ways that are inconsistent with their duties.
A concrete step that pharmaceutical companies could take to avoid these problems is to introduce a management structure that ensures physicians' performance is assessed appropriately. Physicians at every level could be required to develop annual goals that are ethically explicit and appropriately aligned with research ethics principles and corporate ethics policies. For example, a physician planning to conduct a trial in an underdeveloped country could set a goal of providing ongoing medical support for participants in that country after the trial is complete. Another physician might set the goal of implementing a long-term safety study on a new drug to carefully assess its side effects once it is in widespread use. Performance reviews could include assessments of ethical behavior, with rewards clearly tied to exemplary ethical performance.
A more radical change would be to introduce the concept of ethics audits conducted by an outside agency, such as an arm of the Food and Drug Administration. A review of the ethical content of codes of ethics, standard operating procedures, and drug study designs could provide companies with information that could help them maximize the likelihood of ethical drug development. The possibility of external consultants conducting performance reviews of individual physicians might also be useful but would be financially burdensome.
It is difficult to change the deeply embedded assumptions that define an organization's culture. But any attempt to straighten out the problems in the pharmaceutical industry can succeed only if it combines virtuous, educated, empowered physicians with major cultural change. When ethical dilemmas arise, the culture of the corporation plays a central role in influencing an individual's actions. A company's culture provides unwritten rules of behavior for trying times. It tells you what you need to do to be valued. It tells you whom you need to influence to advance your career. It tells you the consequences of making a mistake.
A code of ethics might exist on paper, but the culture of a company might not support the open discussion of ethical concerns. Stories may be passed down about the fate of former employees who raised sensitive issues. Physicians may be made to feel uncomfortable if they raise a concern about product safety. Despite a good performance review, a medical director who resisted conducting a particular trial may find himself passed over for a promotion. The medical function may be viewed as simply a support for marketing activities, rather than as a critical function in its own right.
Physicians in industry are steeped in corporate culture. Although it is recognized that occupations that require extensive education and apprenticeships, such as medicine, may themselves form a culture, (23) conditions are not favorable to support a medical culture for pharmaceutical physicians. They often stop seeing patients, which causes them to lose sight of their primary responsibility. They may work on drugs and diseases outside their specialties, and as a result, stop attending professional society meetings.
Even within industry, cultural connections among physicians are at risk of being lost. Their offices are often located with their product teams, creating geographic distance from other physicians. Opportunities for them to interact with other physicians--to share concerns and compare experiences--may be limited. If pharmaceutical medicine became a recognized field, the creation of a subculture might help physicians find their moral voice in potentially uncomfortable environments.
A healthy corporate culture might encourage discussion of sensitive topics. Patient welfare and scientific progress might routinely be considered before profit, and physicians who helped their companies adhere to this hierarchy might be treated as more valuable employees.
I would like to thank Arthur Caplan, Jon Merz, and Katherine Taylor for helpful comments on earlier versions.
(1.) D. Healy, "The Latest Mania: Selling Bipolar Disorder," PLoS Medicine 3 (2006): 441-43.
(2.) K.P. Hill et al., "The ADVANTAGE Seeding Trial: A Review of Internal Documents," Annals of Internal Medicine 149 (2008): 251-58.
(3.) A. Berenson, "Drug Files Show Maker Promoted Unapproved Use," New York Times, December 18, 2006.
(4.) Scandinavian Simvastatin Survival Study Group, "Randomized Trial of Cholesterol Lowering in 4444 Patients with Coronary Heart Disease: The Scandinavian Simvastatin Survival Study (4S)," Lancet 344 (1994):1383-89.
(5.) J.M. Bathon et al., "A Comparison of Etanercept and Methotrexate in Patients with Early Rheumatoid Arthritis," New England Journal of Medicine 343 (2000):1586-93.
(6.) B.J. Druker et al., "Five-Year Follow-Up of Patients Receiving Imatinib for Chronic Myeloid Leukemia," New England Journal of Medicine 355 (2006):2408-2417.
(7.) Pharmaceutical Research and Manufacturers of America (PhRMA), Pharmaceutical Industry Profile (Washington, D.C.: PhRMA, 2009).
(8.) D.A. Zarin and T. Tse, "Medicine: Moving Toward Transparency of Clinical Trials," Science 319, no. 5968 (2008): 1340-42.
(9.) S.H. Ehringhaus et al., "Responses of Medical Schools to Institutional Conflicts of Interest," Journal of the American Medical Association 299 (2008): 665-71.
(10.) C.D. DeAngelis et al., "Clinical Trial Registration: A Statement from the International Committee of Medical Journal Editors," Journal of the American Medical Association 292 (2004): 1363-64.
(11.) J.E. Mackie et al., "Lessons on Ethical Decision Making from the Bioscience Industry," PLoS Medicine 3, no. 5 (2006): 605-610.
(12.) Roche, "Ethical Standards," at http://www.roche.com/corporate_responsibility/ csr_research_and_development/ethical_standards. htm, accessed April 29, 2009.
(13). Merck, "Conducting Ourselves Ethically and Transparently," at http://www.merck.com/corporate-responsibility/ business-ethics-transparency/priorities-targets-sidebar.html, accessed April 29, 2009; Abbott, "Ethics and Compliance," at http://www.abbott.com/global/url/ content/en_US/40.60.10:10/general_content_00258.htm, accessed April 29, 2009.
(14.) Ibid.; GlaxoSmithKline, "Corporate Ethics and Compliance Programme," http://www.gsk.com/about/corp-gov-ethics.htm, accessed April 29, 2009; Eli Lilly and Company, "Code of Conduct," at http://www.lilly.com/about/compliance/conduct/, accessed April 29, 2009.
(15.) PhRMA, Pharmaceutical Industry Profile.
(16.) P.B. Miller and C. Weijer, "Fiduciary Obligation in Clinical Research," Journal of Law, Medicine and Ethics 34, no. 2 (2006): 424-440.
(17.) E.D. Pellegrino, "Beneficence, Scientific Autonomy, and Self-Interest: Ethical Dilemmas in Clinical Research," Cambridge Quarterly of Healthcare Ethics 1 (1992): 361-69.
(18.) D.R. Buchanan and F.G. Miller, "A Public Health Perspective on Research Ethics," Journal of Medical Ethics 32 (2006): 729-33.
(19.) Pellegrino, "Beneficence, Scientific Autonomy, and Self-Interest."
(20.) U.S. Department of Health and Human Services, "Frequently Asked Questions for the Requirement for Education on the Protection of Human Subjects," at http://grants.nih.gov/policy/hs_educ_faq.htm, accessed April 29, 2009.
(21.) American Board of Medical Specialties, "Our History," at http://www.abms.org/About_ABMS/who_we_are.aspx, accessed May 5, 2009.
(22.) H.S. James, "Reinforcing Ethical Decision Making Through Organizational Structure," Journal of Business Ethics 28 (2000): 43-58.
(23.) E.H. Schein, Organizational Culture and Leadership (San Francisco, Calif.: Jossey-Bass, 2004).
Elizabeth A. Kitsis, "Rx for the Pharmaceutical Industry: Call Your Doctors," Hastings Center Report 39, no. 4 (2009): 18-21.
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