Outcomes research is the systematic assessment of clinical practice. It evaluates all (reasonably held) theories and alternative clinical practices by focusing on the treatment of clinical conditions rather than individual procedures or treatments. Outcomes include those relevant to patients—mortality, morbidity, complications, symptom reduction, and functional status improvement—as well as physiologic or biologic indicators. Outcomes research utilizes multidisciplinary assessment teams and emphasizes new strategies and methods for making inferences both from experimental and nonexperimental data.
The Omnibus Budget Reconciliation Act of 1989 (P.L. 101–239) established the Agency for Health Care Policy and Research (AHCPR) within the Department of Health and Human Services and appropriated funds for outcomes research and particularly for the establishment of the Patient Outcomes Research Teams (PORTs). Eleven PORTs have been funded as of October 1990. Each PORT focuses on a specific acute or chronic condition that occurs frequently, especially among Medicare beneficiaries, and for which risks and costs are particularly high, treatments are particularly variable, and outcomes uncertain. It identifies and analyzes the outcomes and costs of current alternative practice patterns to determine the best treatment strategy.
PORTs are large multidisciplinary, multi-institutional projects that employ larger and more diverse groups of researchers than is typical in health services research. Each PORT includes academic and practicing community-based health care providers and has expertise in pertinent clinical specialties, literature synthesis, research design, epidemiology, biostatistics, economics, decision analysis, survey research, data management, and research dissemination. PORTs conduct at least the following activities: a comprehensive literature review and synthesis on the condition or treatment being assessed; collection and analysis of data including
variations in medical practice and associated patient outcomes; dissemination of findings about effectiveness; and evaluation of the effects of dissemination.
The research being conducted by PORTs is in many ways similar to traditional clinical, health services, and epidemiological research. However, PORTs have several features that justify giving them special attention in relation to conflicts of interest. First, PORT findings will be used in the development of practice guidelines. As such, they can be expected to influence medical practice more directly than the findings of a particular clinical trial. Second, the findings of PORTs are likely to affect reimbursement decisions by third party payers and thus have significant financial implications for both manufacturers of medical devices and drugs and for practitioners who rely heavily on modalities that may be found to be relatively ineffective. Finally, some PORTs may come to have multiple sources of research funding in addition to federal funding.
INSTITUTE OF MEDICINE STUDY
Recognizing the vulnerability of PORT findings to challenges based on conflict of interest, the Institute of Medicine (IOM) was asked to convene a committee to provide points for the agency and PORTs to consider in anticipating and managing conflicts of interest. The nine-member committee, which represented expertise in medical center and research administration, health services and clinical research, law, medical sociology, ethics, pharmaceutical and device manufacturing, and regulation—commissioned background papers and convened a one-and-a-half-day workshop to discuss issues relevant to conflicts of interest in PORTs. The committee was not charged to develop formal recommendations, nor does it regard its points to consider as such.
DEFINING CONFLICT OF INTEREST
Conflict of interest arises in a situation in which (1) one is in a fiduciary relationship with certain others, and (2) one's financial or professional self-interest substantially differs from the interests of those others. The concern with conflicts of interest arises in biomedical research because of the possibility that such conflicts, both real and perceived, may erode scientific objectivity and engender the loss of public trust.
Because PORTs conduct research for the public benefit, PORT researchers have fiduciary obligations to the public. Yet their interactions with other groups, although necessary and even desirable, in some instances risk creating conflicts of interest. The committee does not, however, consider financial conflicts of interest to be the only, or even necessarily the most important, sources of bias in PORT research. For researchers, desire for public recognition, publication, grant renewal, career advancement, or tenure may exert strong inducements to produce positive results. These professional conflicts of interest need not be conscious decisions on the part of an investigator; nevertheless, intellectual attachment or commitment to a particular scientific theory pose possible conflicts.
Financial relationships that may give rise to conflicts of interest take two typical forms for clinical researchers. One type is an individual researcher's financial relationship with a company that owns a technology that the researcher is evaluating. These relationships include ownership of stock or stock options; management or executive positions with such companies; royalties from licensing of intellectual property rights, including patents on inventions, copyrights (e.g., computer software), and sale of other proprietary materials; and consultant positions and honoraria paid for lectures. A second type of financial relationship is the support a company provides to the university where researchers conduct their work; such support may come by a variety of mechanisms, including technology-transfer cooperative agreements to promote rapid commercialization of products.
In the last decade, as such university-industry relationships have increasingly included the biomedical sciences, concern has been expressed in public and professional circles about adverse effects on research and especially on the independence of researchers. However, very few comparative assessments have been published on the risks and benefits of the variety of relationships adopted by academic centers, industry, and external organizations including the federal government. Policymakers have neither rigorous data about risks and benefits nor accurate assessments of the effects of policies meant to diminish the risks and enhance the benefits.
The trend over the past 10 years has been for government agencies and academic organizations to mandate or strongly advocate full investigator disclosure of any financial interests in businesses that might profit from the products or procedures under study. The responsibility of academic institutions for oversight and management of conflicts of interest has also been increasingly stressed. Recent reports issued by the American
Association of Medical Colleges and the Association of Academic Health Centers address the management of conflicts of interest in the university and particularly in the academic health center. Although these works were helpful to the committee's deliberations, special aspects of PORTs remain to be addressed.
PORTs are a new hybrid entity which encompasses academic medical research leading to peer-reviewed scientific findings and a ''quasi-regulatory'' role directly related to public policy and health insurance payment questions. This hybrid responsibility confers special expectations on PORTs and argues for well-defined, irreproachable standards to address the appearance of conflict of interest as well as its actual occurrence. PORTs may require a level of scrutiny and a threshold of acceptability that are higher than those established for other research efforts—perhaps comparable to those for judges, public officials, and others with fiduciary responsibilities. Existing institutional guidelines and procedures may thus not be adequate for this kind of entity or for multi-institutional PORTs and nonuniversity clinicians.
Other concerns regarding conflict of interest in PORTs include the following: congressional expectations regarding the cost-containing effects of PORT findings may result in a powerful potential bias. A concentration of expertise in PORTs may give them a continuing advantage over other researchers in obtaining grants and contracts, disseminating findings, and influencing insurance reimbursement and other policies affecting care of the medical condition on which each PORT specializes. Their findings will not be replicable (or at least not easily) and will accordingly be difficult to challenge. Moreover, the committee noted that the use of qualitative judgments in outcome assessments, in contrast to the quantitative end points usually found in clinical research, will make subtle biases much harder to discern. PORT researchers are also vulnerable to biases arising from professional and collegial ties to the subjects and the practitioners being studied. All these issues raise concerns about the effects of conflicts of interest and make it important to provide access to valuable PORT data bases to challenge and confirm their findings and for secondary analysis. Further, evolving PORT methods, which include prospective data collection from patients and community-based clinicians, will attract outside funding, spin-off ventures, and consultancies. All these developments promise better technology, better information for medical decision making, and more rapid medical progress, but they also pose difficult questions regarding conflicts of interest. Freedom of communication among PORT investigators—a tenet of science generally—and between PORT investigators and manufacturers of technologies being evaluated pose special problems. When manufacturers provide additional funding to evaluate technological modifications and new practices, medical knowledge
may be pushed forward more rapidly, but with a potential diminution of scientific objectivity. Similar issues arise when PORT members enter into financial arrangements related to intellectual property rights and spin-off ventures. Equity interests of PORT investigators in companies whose products are being evaluated present special hazards in creating an appearance—and possibly the reality—of conflict of interest.
MODELS FOR ADDRESSING CONFLICTS OF INTEREST
Two models can be used to approach conflicts of interest. One would prohibit all relationships that might give rise to a conflict of interest unless an overriding social benefit could be established. The other would allow most relationships and rely on a strong disclosure and peer review process to protect the public interest. Although differing in their starting points and in their effect on particular research projects, each model can incorporate similar means of reducing or managing the effects of a conflict of interest: mandatory disclosure, mechanisms of financial distancing, self-regulation, defining categories of acceptable activities and implementing oversight of such activities, and defining unacceptable activities and implementing prohibitions or, when necessary, sanctions.
POINTS TO CONSIDER
This report suggests points for consideration by PORTs and their institutions, AHCPR, the health services research community, industry, and Congress regarding conflicts of interest in outcomes research. The committee believes that the primary role of AHCPR should be to insist that institutions have a method in place for acknowledging, exploring, and managing these potential conflicts. The report bases its points to consider on a number of assumptions and observations about PORTs and PORT research:
Like other scientists, PORT researchers seek to maximize the validity of their inferences by identifying sources of bias and by minimizing the effects of those biases on their findings.
The varieties of PORT relationships with other entities are evolving, and any pitfalls resulting from financial and professional conflicts of interest cannot yet be well delineated.
PORTs may be exposed to accusations of conflict of interest because of connections to industry, professional associations, and the like, possibly with the intent of discrediting their findings when such results are
at odds with the interests of other parties.
PORT investigators need guidance in recognizing a potential or real conflict of interest and knowing when to disclose it.
Each PORT or its home institution should have in place an appropriate mechanism by which relevant conflicts of interest and biases can be revealed and addressed.
Each prospective PORT should be required in its funding application to file copies of the conflict-of-interest policies of the home institution and of its proposed subcontractors and to describe the process it will use to manage conflicts of interest.
Requirements regarding conflict of interest should be at least as stringent as those that apply to clinical investigators. Where institutional rules distinguish between bench and animal research on the one hand and clinical trials on the other, PORTs should be subject to the rules that apply to the latter.
Methods of dealing with conflict of interest include disclosure, followed by assessment and management or, where essential to the integrity of the research, outright prohibition. The PORT members and their institutions are best placed to determine the process by which they will manage conflict. Important aspects of such a process include education about conflicts of interest for researchers, faculty, and students; clearly stated expectations for early and complete disclosure of relevant interests; well-formulated, well-implemented institutional process for responding to disclosures; and emphasis on the role of the principal investigator in managing conflicts.
Collaborative research agreements with industrial entities (firms) should ensure freedom to publish the outcomes of studies, whether favorable or unfavorable, and latitude for communication among PORT investigators and industry.
Generally, PORT researchers (and their immediate families, including minor dependents) should not be equity holders in firms that produce technologies used for the conditions being studied.
To counteract nonfinancial sources of bias, such as those arising from professional loyalties and training and from other academic affiliations, PORTs should actively encourage internal and external scrutiny and should ensure that the team has representation from the full range of relevant clinical and scientific disciplines.
PORTs of necessity rely heavily on observational studies, incomplete data bases, and qualitative outcomes, and their findings are no substitute for traditional clinical trials and should not be the sole basis for clinical or public policy decisions.
Outcomes research (and PORTs in particular) has been funded for a variety of reasons including improvement in information, knowledge,
quality of care, and rationalization of the nation's allocation of health care resources. Although there is a hope, if not an expectation, that PORTs will save money for federal programs, this is unlikely in the short run. PORT teams should not be overtly or subtly required to recommend cost-saving practices as a basis for renewed funding.
Since AHCPR cannot assume the role of sole supporter of patient outcomes research, PORTs may need, or even require, other sources of funding, much of which may come from industry. The manner in which such funds are juxtaposed with agency support, however, needs serious consideration in each case and careful management to safeguard the conclusions of PORTs from the appearance or reality of a conflict of interest.
Uniform standards for conflict of interest and self-dealing in PORTs are not needed at this time. If AHCPR does establish minimum agency standards, it should do so in collaboration with the National Institutes of Health.
Grant specifications should include a requirement that both internal and bona fide external investigators and analysts may have reasonable and timely access to PORT data.
Outcomes research as exemplified by PORTs holds out the promise of greatly improving the value and effectiveness of the health care system. The fear of unresolvable conflict of interest should not inhibit commitment to outcomes research or the continued evolution of what must be seen as a bold new "social invention" on the part of Congress.