Sources of Concern About Conflicts of Interest in PORTs
Chapter 2 examined several ways in which PORTs are different from other clinical research and that might therefore raise special concerns about conflicts of interest. Chapter 3 defined and described several kinds of university-industry relationships that may give rise to conflicts. This chapter describes in more detail 11 issues (Box 4.1) that are especially pertinent to PORTs. The first seven issues are inherent to PORTs as they are currently configured and funded by AHCPR. When non-AHCPR funding is added or as PORT members engage in new ventures related to their PORT research, additional concerns may arise; these last four issues are described in the latter part of the chapter.
ELEVEN ISSUES OF SPECIAL CONCERN
PORTs as Hybrid Entities: Research and Quasi-Regulatory Functions
PORTs as a Public Trust for Development of Scientific Knowledge
PORTs are highly visible examples of academic science and technology; as such, they are part of a sizable public investment in academic medical research that is intended to improve health. Such government-supported basic and applied biomedical research has over the decades resulted in major advances in scientific knowledge (Hamburg and Nightingale, 1984; Colloton, 1989; Schroeder et al., 1989).
There are three deeply held public views about these undertakings. First, academic science is seen by many as an engine of creativity and innovation that drives social welfare. Biomedical research has led to scientific discoveries and major technological applications for the care of
individual patients. Indeed, the academic medical center plays a central bridging role in the development and transfer of health care technology between industry and medical practice, regularly participating in the development, diffusion, and appraisal of appropriate applications and cost (Rettig, 1987). PORT investigation, a young and rapidly evolving science, consists of methods for evaluating and improving medical practice by considering the effectiveness of care through outcomes research. It is thus at the heart what has been termed "the new technology assessment" (Fuchs and Garber, 1990).
Second, academic scientists, through their participation in hundreds of advisory and peer review committees, are counted on as a source of impartial advice to the public and to funding and regulatory agencies; any challenges to their impartiality are seen as highly significant and are widely publicized. When serving as advisors on matters of public policy, academic scientists must feel free to publish, share data, and speak out in the public interest (Krimsky, 1988). Indeed, for the advisory process to work effectively it must secure unbiased, objective advice from individuals who are financially disinterested in the areas in which they consult. PORTs in particular have been designated by Congress to provide such advice to practitioners and to the Medicare program. By contrast, industrial scientists have visible affiliations with business and are not expected to be impartial.
Third, in undergraduate and graduate training, academic science teaches scientists, citizens, and future political leaders how science is conducted. To the extent that PORTs become a model for complex health services and clinical evaluation research of the future, they will certainly affect the values of graduate students. Moreover, the values of science that are learned in institutions help form each generation's social decision makers (Grobstein, 1988). All three of these public views—promoting health, providing impartial advice, and preserving the values of scientific inquiry—although not unique to PORTs, are important to consider when examining conflicts of interest.
PORTs as a Quasi-Regulatory Process
Is there good reason at this point to single out the research activities of PORTs for special requirements? PORT research is similar to other forms of research that receive intense and increasingly public examination from the standpoint of conflict of interest. PORT studies are also different from other types of biomedical or social science. Most prominently, PORTs will directly influence health care. Although PORTs will not themselves make decisions about insurance coverage for the
medical procedures they study, the results of their research will be a key factor in these decisions. Indeed, that is surely one reason why AHCPR has focused PORT research on conditions affecting chiefly the elderly beneficiaries of Medicare; furthermore, PORT findings may have more effect on professional norms than an individual clinical trial could have, in part because of the diverse clinical specialties involved and in part because of the likely wide visibility and dissemination of results in many clinical journals and health services research publications.
Protecting PORT Credibility
PORT findings are likely to be controversial from the viewpoint of clinicians, manufacturers, and other interested parties; whether they are ''positive" or "negative," they may not be accepted without struggle. That struggle will probably involve examining all potential sources of bias, possibly with the intent of damaging the credibility of the PORT findings. A likely tactic would be to call into question the sources of PORT funding as a source of bias or the possible biases of its members.
These considerations argue for well-defined, irreproachable standards to address the appearance of conflict of interest as well as its actual occurrence. They may also call for a level of scrutiny and 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.
PORTs are strengthened by their multidisciplinary character and multisite teams, as well as by incorporating the multiple perspectives and literature of each discipline into their research. This diverse participation can mitigate the possibility that biases of individual investigators will distort the final analysis (Lave, 1990), a feature that PORTs may be required to demonstrate convincingly to would-be detractors.
Expectations of Cost Savings
Workshop participants and committee members noted the conflict inherent in a mandate from Congress that is intended not only to improve medical care but also to control federal expenditures. Some observers see this savings as the primary motivation for congressional funding of outcomes research. For this reason, there is an implication that AHCPR, or individual PORTs, may be at risk of losing their funding if their findings do not lead to cost savings. Consistent findings of under use of expensive technologies might be even less welcome.
In addition to the conflict engendered by the federal government's interest in cost savings, insurance companies might also place subtle pressures on PORTs. For example, those interested in reducing practice variations might develop consulting arrangements, offer to fund additional PORT research, or allow access to their data in hopes of identifying excessively costly practices. The intended or unintended effect of the PORTs' work and of collaboration with third party payers whether public or private, may be to reduce access by the public to various treatments. These pressures, which are not generally present in traditional clinical research, were recognized quite early by supporters of outcomes research. With respect to government funding, one important factor mitigating such pressure is the placement of MEDTEP in the U.S. Public Health Service rather than in the Health Care Financing Administration, even though much of the early initiative for effectiveness research originated in the latter agency (Roper et al., 1988). This decision was made because both DHHS and Congress feared that if the program were located in the Health Care Financing Administration, it would be seen as more interested in saving money for federal programs than in promoting good care for all citizens. PORTs thus have some protection from possible accusations of being tied too closely to federal cost-savings objectives, but the threat is not completely answered.
Concentration of Expertise
Many participants in the IOM workshop were concerned about the implications of the concentration of expertise that will occur in the multidisciplinary PORTs (a problem not unique to PORT research). This concentration may constitute an imprimatur (some observers have used the term "taxi medallion") based on expertise, credibility, and long-term funding that gives PORTs an advantage in continued funding and makes challenges to their findings difficult (Lave, 1990). It also makes the effect of bias at any stage of the research less easily or quickly detected. Other workshop participants disagreed with this pessimistic assessment. In their view, particularly in fertile clinical areas such as cardiac diseases, funding for PORTs is not sufficiently large to make PORT studies the dominant efforts in their field. In any case, understanding the ramifications of a concentration of people, experience, knowledge, and research support may have to await several years of sustained PORT funding—perhaps well past the first five years of the PORTs that are now operating.
Subjective Judgments and Multidimensional Outcome Assessments
The work of PORTs will necessarily involve many areas of uncertainty, and these will aggravate the risks of private and professional conflicts of interest. Although clinical research often has a subjective element, judgments in PORT research depend more heavily than do those in most clinical research on multidimensional, self-reported outcome data from patients. PORT investigators must also make subjective judgments and interpretations when weighing the importance of various health outcomes. Important dimensions of health status and quality of life include death, discomfort (both physical and psychological), various aspects of functioning (including physical, cognitive, social, and role functioning), and general aspects of well-being (Lohr, 1988; Patrick and Deyo, 1989; Patrick, 1990; Patrick and Bergner, 1990). Related economic outcomes might include both direct medical costs and indirect costs such as loss of productivity; opportunity costs, which describe the costs of alternative uses of resources, might also be estimated (Fries and Spitz, 1990). The measures selected to reflect outcomes (both health and economic), as well as the judgments derived from these measures, may be more vulnerable to bias than those based on traditional physiologic or anatomic end-point data, and these biases may be difficult to discern.
Choosing important outcomes and ranking them in comparison with other outcomes are likely to be influenced by professional concerns, financial interests, and personal preferences. Outcomes of a very risky and costly procedure, for instance, are likely to be viewed differently by the manufacturer of a device used in the procedure, a surgeon who derives satisfaction from achieving even a small benefit, or by patients with different tolerance for symptoms contributing to indications for the procedure.
Even where consensus on appropriate outcomes is achieved, developing a set of reliable, valid, and practical outcome measures for application to the diverse clinical conditions examined by PORTs is extremely challenging and complex. The work that must be done in choosing among existing measures and, when necessary, devising new or combined measures has just begun.
Researchers must also exercise subjective judgment in determining what materials are to be included in meta-analysis. Some published studies and most unpublished studies may be excluded because they fail to meet the inclusion criteria established by PORT investigators. Another possible source of bias is the selection of methods to conduct the necessary ''cleaning" and transforming of insurance claims data tapes; yet, these methods generally are not described in detail.
Use of such data for decision analysis and the construction of guidelines for clinical decision making involves more uncertainty. The apparent precision of decision-analytic techniques and algorithms for care may lend weight and importance to information that must be treated more cautiously. Often data to provide probabilities for a given risk or benefit are missing or very limited—for instance, only mortality data may be available. A range of probabilities derived from several studies may differ enough that investigators will not be able to make specific clinical recommendations with confidence. Thus, another area of possible bias is in the dissemination of findings through practice guidelines. The science of developing clinical practice guidelines, however, is still so rudimentary and sketchily documented that these activities should also be considered highly subjective (IOM, 1990).
Biases Arising from Ties to Professional Colleagues and Associations
PORTs are designed to examine services that are costly or prevalent (or both) and that consequently are likely to provide a large proportion of the income of health care professionals, particularly in specialties related to the interventions being evaluated. PORT researchers must rely on the active participation of individual practitioners and professional societies to enroll patients in their studies and to conduct some primary data collection about patient preferences regarding risks and outcomes.
For example, the outcome assessment team at the University of Washington is investigating low back pain, a problem that is the second leading reason for all physician visits and the leading reason for visits to orthopedic surgeons and neurosurgeons. There are large variations in per-person rates by geographic area in the use of surgery, hospitalization, and diagnostic technology. The value and sequencing of diagnostic tests for improving the patient's quality of life (the primary purpose of treatment) are not well understood. The scientific evidence for the efficacy of most treatments is limited, yet the rate of lumbar spine surgery is increasing. The PORT will examine three surgical procedures on the spine—laminectomy, discectomy, and spinal fusion. Assessment of symptom resolution and improvement in functional status will be examined in a cohort study conducted by the Maine Medical Assessment Foundation. Most of the orthopedic surgeons and neurosurgeons in the state of Maine who perform surgery on the spine will contribute patients to this cohort study (Deyo et al., 1990).
PORTs generally have both regional and national advisory boards that include representatives of the specialties and other professional
associations affected by their research. This is a source both of strength and of potential bias; consequently, all PORT investigators will need to develop procedures to mitigate unconscious biases arising from a desire not to alienate colleagues and professionals who are cooperating and contributing patients to the PORT projects.
Another source of bias may arise in relation to professional societies and health delivery systems. PORTs may enter into consulting agreements with such groups to support them in related research that confirms or refutes findings or tests new technologies that might increase the range of skills of their members. The desire to help these groups may be another source of bias. This type of bias could also occur if PORTs begin to evaluate alternative health care settings (e.g., hospital intensive care, home care). Interested and concerned groups in this case would include the relevant health care organizations.
Access to Data
Workshop participants and members of the IOM committee were concerned about ensuring access to the data collected by PORTs to allow subanalyses and reanalyses by other groups. Such secondary analyses may well be valuable in their own right; they also offer an opportunity for skeptical audiences to confirm (or refute) PORT findings.
Access to Medicare data analyzed by PORTs is subject to certain restrictions. The same general points probably apply as well to insurance data purchased from private carriers or obtained from state data consortia. General access to these valuable data bases can be facilitated or restricted by AHCPR (through grant and contract specifications) and by the PORTs themselves. However, PORTs can, if they choose, constrain other groups analyses of already collected data. This is a common problem in science (e.g., see Cantekin et al., 1990) that presents no unique obstacle unless it is compounded by a conflict of interest.
Adequacy of Existing Institutional Guidelines
Participants at the IOM workshop emphasized the importance of institutional monitoring, management, and resolution of conflict-of-interest issues. PORTs are multi-institutional (see Box 2.1); thus, investigators collectively have numerous "home" institutions. PORTs may, in addition,
have subcontracts with other institutions. As a result, single-institution policies are likely to be inadequate for these PORTs.
AHCPR considers the primary grantee or lead institution to be responsible for managing conflict-of-interest situations. Generally, the lead institution accepts the judgments of the institutions with which it has subcontracted and would expect to be notified of any relevant conflicts of interest that were revealed. Several participants at the IOM workshop and other health services researchers who have PORT subcontracts noted, however, that they are unaware of their own institution's policies on conflicts of interest or that those policies have not been revised for many years and may no longer suffice in the PORT environment. Further, awareness and acceptance by PORT members of a lead institution's policies represent only the first step towards avoiding conflict of interest. Should questions and issues arise about conflicts of interest in a PORT during the five-year course of conducting a study, the lead institution will need to have a mechanism for responding to these questions.
Nonuniversity Clinicians and Their Patients
Another special issue for PORTs is the research and conflict-of-interest implications of including or excluding nonuniversity clinicians and their patients. For research, the exclusion of certain clinicians might result in a nonrepresentative group of patients, thus jeopardizing the generalizability of the PORT findings. In terms of conflict-of-interest considerations, nonuniversity clinicians who have not been exposed to institutional conflict-of-interest guidelines may be unused to, and find objectionable, queries about their finances.
Matters that raise the issue of conflict of interest are not, however, foreign to nonuniversity clinicians. There have been numerous reports, for example, of brokers who offer physicians stock in companies that manufacture drugs that the physicians presumably prescribe (Morris, 1990); offers of direct payment for prescribing certain medications (Wolfe, 1990); of drug companies that offer to pay for conferences as an inducement to try a new product (Jenike, 1990; Schonberg, 1990, Wolfe, 1990); and of investment opportunities in laboratories to which physicians could refer their patients for testing (Rodwin, 1989). That such inducements are common does not make them acceptable or lessen the need to guard against their influencing PORT findings. If clinicians in private practice are to participate in PORT research, as seems both necessary and appropriate, attention must be paid to including nonuniversity clinicians in the administration of any prohibitions, limitations, or disclosure
requirements that may be implemented to protect against conflict of interest.
Private Funding for Technological Modifications and New Practices
The issues above pertain to PORTs supported only with federal funding. PORT methodology is evolving, however, and now may include the collection of prospective data involving new types of health status measures as well as patient-administered outcome measures among specified (although not randomized) groups of patients. Aspects of controlled trials thus may come to be incorporated in PORT design, and private funding of many kinds may be grafted onto core PORT funding. These factors, as well as the more usual questions related to equity interests in products under evaluation, raise special issues regarding conflict of interest, and are described in the remainder of the chapter.
During PORT investigations, which presently are expected to last approximately five years, PORTs are likely to need (or at least attract offers of) additional funding from industry, other federal or state agencies, and insurers. MEDTEP expects PORTs to evaluate existing practices, but it is quite possible that these practices will change during the grant period. Although current annual funding levels per PORT are approximately $1 million (direct plus indirect costs), there is no guarantee that this level of support will be maintained in the future. In addition, more problems invite in-depth investigation than can be studied with current AHCPR funding. As ready-made groups of investigators and study sites, PORTs are an attractive vehicle for industry research funding. The committee envisions three main kinds of agreements: additional study arms, secondary protocols, and consulting and other financial arrangements. The development by PORT investigators of spin-off ventures and copyrights on intellectual property rights are yet other possible financial arrangements.
Additional Study Arms
Corporate sponsors recognize the potential of PORTs to influence significantly the adoption and dissemination of their innovations. Thus, mixed financial agreements might support the investigation of new devices or drugs as added study arms within an initial PORT study. With an agreement of this kind, PORT researchers could be assured that their findings represented up-to-date practices; physician and patient decision making could be well served by having all alternatives included in a study.
In addition, private, rather than public, funds could be used to support any evaluations with possible commercial value.
Despite the potential advantages of this form of collaboration, the committee also sees certain hazards. One is concern about the scientific legitimacy of studies that are developed as contracts rather than as peer-reviewed grant proposals. Another concern is the implication of any special agreements restricting communication or publication of results (discussed in greater detail in a later section) or otherwise compromising the rights of the investigator or university. This may be especially problematic for institutions that may come to be involved in PORTs at some later time and that do not have the well-established review and monitoring systems of PORTs funded earlier.
Industry might also use such a relationship to "advertise" its association with a PORT. This might, in turn, raise doubts externally about the objectivity of the PORT effort. Moreover, PORT findings that endorse a product whose evaluation has been paid for by its manufacturer appear suspicious, giving an appearance of conflict of interest even where none exists. For all these reasons, the expectations and limitations of the collaboration must be made clear when agreements are fashioned.
A second possible form of PORT-industry collaboration is the performance of secondary protocols by one or more PORT investigators concurrently but separately from PORT investigations. Assignment of patients to one study rather than another might represent a nonscientific or scientific conflict of interest. For example, a nonscientific conflict of interest might occur if an investigator whose continued secondary funding depends on enrolling a sufficient number of cases recruits patients preferentially to the secondary protocol. A scientific conflict of interest might occur if systematic recruitment weakens the power of the PORT study, (i.e., the ability of the investigators to find statistically significant differences or to draw strong and proper inferences from their data).
Consulting and Other Financial Arrangements
A third form of PORT-industry collaboration can occur if members of a PORT are offered consulting arrangements with manufacturers that produce related products and services or with a private consulting firm that is under contract with the manufacturer. Companies would benefit from having the most current information in designing their own studies and
using the most advanced health status measures. From the vantage of clinicians and their patients, such industry studies would benefit in their design and methods from the expertise of senior investigators in PORTs. Nothing in PORT grants now precludes consultation or other arrangements with firms that are developing devices or drugs related to those under evaluation by the PORT or that are competitive with those under evaluation, yet this would seem to pose a hazardous potential for conflict of interest.
Spin-Off Ventures and Intellectual Property Rights
Another form of industry-PORT relationship might occur when, in the course of their study, members of the PORT develop special expertise. This might, for instance, involve special software for claims data analysis, survey tools to assess outcomes, approaches for assessing utilities or patient preferences, and educational programs describing alternative treatments. Primary data collection on patient preferences for various outcomes could be seen as extensive pilot testing (Asch, 1990). Over time the accumulation of such expertise or related products could lead to the monitored or unmonitored formation of businesses in which members of the PORT have a financial interest (McNeil and Roberts, 1990). Although such developments would likely serve many social goals, members of PORTs would also be uniquely positioned to benefit from these commercial applications.
Other expertise might also be commercialized in a manner analogous to the technology transfer so encouraged by tax provisions and other legislation. For instance, knowing that insurance companies might be eager to purchase information on the appropriateness of various medical practices, sideline consulting firms (developed by PORT or nonPORT investigators) might provide services designed to assess appropriateness using relevant intellectual property developed with federal PORT funding.
Equity Interests of PORT Investigators
As with other forms of research, members of PORTs are at risk for conflicts if they have equity interests in the subject of their research or in related or competing companies. Because PORTs focus on existing products and services with direct market implications for their findings, such collaborations may present heightened opportunities for exploiting inside information for financial benefit (Asch, 1990).
Freedom of Communication Within PORTs
The evolving methods and large size of PORTs require flexibility and an ongoing exchange of information among investigators and with industry; when industry provides funding, however, it may seek to protect patent rights and investment by limiting the exchange of information. As described in Chapter 2, secrecy has become more common in the field of biotechnology (Blumenthal et al., 1986a,b; Krimsky, 1988). To the extent that voluntary or involuntary restrictions on free discussion inhibit PORT evaluations, they represent a conflict of interest for PORT researchers (Eisenberg, 1988).
In particular, when agreements are made between manufacturers and biomedical researchers, they commonly include so-called secrecy and exclusivity clauses temporarily restricting the investigator from interactions that might compromise the patentability or competitive advantage of the product at issue. For instance, such clauses might prohibit, except with the manufacturer's approval, the disclosure of confidential proprietary data, or knowledge pertaining to the research, development, marketing, or any other aspect of the company's products. Secrecy clauses might restrict the freedom to publish results or to discuss information about the products that are being evaluated by a PORT. Exclusivity clauses refer to restrictions on PORT members, when they are acting as consultants, that prevent them from consulting with or communicating with competing companies. For instance, a clause of this sort might prohibit an investigator from consulting with any other person or entity on matters pertaining to the areas covered by the agreement for a stated time period.
Some observers worry that freedom of communication among all PORT investigators could be compromised if collaboration requires adherence to overly restrictive secrecy and exclusivity clauses. This in turn might jeopardize, or be perceived as jeopardizing, the work and results of the PORTs (both individually and collectively).
Another concern is related to possible restrictions on publication. When industry funds the evaluation of an alternative treatment as part of what is essentially federally funded research, the risks in terms of overall outcome should be understood. "Good" results can be an enormous advantage to the company, but "bad" results are possible. If the results of a PORT evaluation are not encouraging, the company might wish to restrict publication of the data. On the other hand, if the data are very positive, the manufacturer might wish to publicize them widely (or constrain any counter analyses).
This chapter describes eleven sources of special concern about conflict of interest: (1) PORTs as a new hybrid entity having both academic medical research and ''quasi-regulatory" functions; (2) congressional expectations regarding the cost-containing effects of PORTs; (3) the concentration of expertise in PORTs; (4) PORT use of qualitative, subjective, and patient-reported qualitative judgments in outcome assessments; (5) the potential for biases arising from professional and collegial ties to the nonPORT practitioners; (6) the need for access to PORT data bases; (7) the possible inadequacy of existing institutional guidelines for PORTs; (8) the likelihood of private funding to evaluate technological modifications and new practices; (9) of financial arrangements related to spin-off ventures; (10) of bias resulting from equity interests held by PORT investigators in companies whose products are being evaluated; and, (11) the need to ensure freedom of communication within PORTs despite university-industry collaborative agreements. Ways to approach these conflicts of interest generally and with reference to PORTs in particular, are taken up in Chapters 5 and 6 respectively.
Box 4.1 Sources of Special Concern About Conflicts of Interest in PORTs