Clinical Research in the ManagedCare Environment

Barry D. Lebowit%, Ph.D.

Gary L. Gottlieb, M.D., M.B.A.

The authors present the conclusions ofa workshop devoted tothe challenges to clinical research in the changing environmentofmanaged care and health care reform. They identify prob­lems and concerns with current conditions and discuss prom­ising opportunities/or new approaches to research. (AmericanJournal of Geriatric Psychiatry 1995; 3:21-25)

Health care in the United States is under­going profound change. Beginning

with cost-containment, moving throughmanaged care, and, ultimately, concludingin health care reform, the nature and char­acteristics of the system are in flux. What­ever the final shape of the system, it will becharacterized by vertical integration of com­munity facilities, private practice physicians,and tertiary care with an increased emphasison primary care. Other systemic character­istics will include proliferation of ambula­tory care, geographic coverage, broaderprice reductions, and redesign of incentivesencouraging cost-control rather than en­hancement of financial reserves.

Clinical research in the mental disor­ders of late life is carried out, in large part,in specialized tertiary care academichealth centers that may also be affiliatedwith other facilities, such as the Depart­ment of Veterans Affairs Medical Centers,nursing homes, and chronic care facilities.The future of the structure, function, andviability of these institutions is precarious

in the emerging health care system.1

A workshop of clinical investigatorsmet in April 1994, under the auspices of theMental Disorders of the Aging ResearchBranch of the National Institute of MentalHealth, to consider approaches to the nur­turing and continued development of re­search in these new circumstances.

Three general areas were discussed:sources of funding for clinical research,challenges to current methodologies, andopportunities emerging for new ap..proaches.

SOURCES OF FUNDING

Clinical research must build on the clinicalcare of patients. The direct cost for most ofthis care is usually derived from healthinsurance or out-of-pocket payments byconsumers. Research funding usually sup­ports only procedures or treatments that areconsidered experimental or incremental tostandard care. Greater outside control of

ReceivedJune 21,1994; revisedJuly 13,1994; accepted July 20,1994. From the National Institute of Mental Health,Rockville, MD. Address correspondence to Dr. Lebowitz, Mental Disorders of the Aging Research Branch, NationalInstitute of Mental Health, Room 18-105, 5600 Fishers Lane, Rockville, MD 20815.

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Clinical Research in Managed Care

resources and of the process of patient caremay limit access to patient populations andfunding for aspects of the care that theyconsume. For example, expensive diagnos­tic procedures like neuropsychological test­ing and magnetic resonance imaging thatare necessary clinically and can provide keyresearch data are more likely to be disal­lowed by managed health systems.

The funding for research in the mentaldisorders of late life is overwhelminglybased on individual grants from fundingagencies of the federal governnlent, partic­ularly the National Institute of Mental Healthand other units of the National Institutes ofHealth. The cOJnpetition for project-specificfunds has grown particularly intense in thistime of budgetary restraint, and budget re­ductions are invariably required even forthat relatively small proportion of applica­tions that are funded. Average grant size,yearly growth, and project expansion are alltightly controlled. Research personnel sala­ries usually account for the bulk of a projectgrant award, and the workshop participantsconsidered it unlikely that patient care costscould be included as a greater part of aproject budget.

Private sources, including foundationawards and individual gifts, are usually tar­geted to large-capital campaigns or are re­stricted to capital investments or generalprogram operations. Many foundations usemost of their research funding to supportnew investigators in helping launch theirresearch careers. New investigators are alsosupported through the increasingly frequentuse of the creation of "termU chair endow­nlents-modest annual gifts for a fixed pe­riod of time supporting the appointlnent ofa new faculty member and providing salarysupport to reduce requirements for clinicalresponsibilities.

Pharmaceutical-company-supportedclinical trials have proven useful in thedevelopment of a research infrastructureand in the retention of technical staff innU111erous acadelnic health centers. Clinicaltrials are llseful in the recruitment of pa-

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tients for other types of studies as well.Treatment, whether experimental or estab­lished, was identified as a critical induce­ment to participation for subjects for allclinical research. Commercial clinical trialorganizations, for reasons of efficiency andlimited focus, have displaced acacleluic cen­ters as the predominant sites for new drugstudies, however. Drug studies in non-aca­demic settings rarely support the adjunctivestudies of basic mechanisms or clinical re­sponse differentials that have no direct Inar­keting implications. This fact is eroding thecapacity of academic investigators to de­velop clinical research.

State-funded mental health research in­stitutes have nlade itnportant contributionsto the clinical research infrastructure bysupporting bed costs, laboratories, andother services. Only a few of these institutesrelnaio, and limitations on mental healthbudgets have severely restricted their activ­ities. Participants underscored the import­ance of continued state support for theseinstitutes.

The Medical Centers of the Departmentof Veterans Affairs (the VA) also provide animportant foundation for acaden1ic clinicalresearch. The VA, with its tradition of actingas an academic liaison, has developed animportant capacity for clinical research sup­ported within its own funding system andused as a resource for other sources ofresearch funding. Investigators are increas­ingly concerned, however, that the VA pop­ulation is limited in diversity, representedby a predominantly male, socioeconomic­ally disadvantaged population suffering adisproportionately high prevalence of sub­stance abuse.

The General Clinical Research Centers(GCRC) program of the National Center forResearch Resources of the NIH is anotherkey resource for clinical research. Gene'sfacilities are available at Jnany academicmedical centers and provide bed costs, lab­oratories, biostatistical consultation, andother components of the clinical researchinfrastructure. Investigators who are able to

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gain access to these resources have foundthe GeRe to be particularly valuable inundelWriting S0111e research costs, espe­cially those associated with nornlal controlsubjects.

CHALLENGES AND CONCERNSREGARDING CURRENT

METHODOLOGIES

\Vorkshop participants endorsed the needto reconsider the full range of researchquestions, methods, and approaches usedin clinical research. For exanlple, the tradi­tional use of inpatient hospital settings tosupport research is likely to be replaced bythe use of ambulatory and other less intensecare sites.

Most observers acknowledge thathealth care delivery is currently flawed: tooll1any people cannot gain access to appro­priate care in the current patchwork ofprivate insurance and public entitlements;routine care is often provided in emergencyand urgent care sites; the specialty andsubspecialty sectors dwarf primary care re­sources; and rehabilitative and long-termcare is often provided in the acute setting.A fortuitous outcome of this disorganizationis that clinical investigators in the academichealth setting have had access to large,diverse, and clinically heterogeneous popu­lations. This sample base has provided suf­ficient variability to allow for furtherrefinement and testing of hypotheses re­garding etiology and pathophysiology, clin­ical course, response to treatment, andlong-term outcome of numerous mental dis­orders.

As the health care system is changedand vertical integration becomes more com­mon, tertiary care facilities are becomingone component of complex systems thatinclude community hospitals and primarycare practices. As part of the creation ofhealth care systems, workshop participantspredicted pressure toward standardization

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Lebolvi/z and Gottlieb

of care through the use of clinical practiceguidelines2 in prin1ary care and cOlnn1unitysettings. These guidelines were predicted toresult in the diversion of insured patientsaway froll1 Clcademic health center facilities.Outcomes derived from these changes inthe process of care will require evaluationof effectiveness and other parameters ofquality. This redistribution of patients willsubstantially affect clinical research becauseit will constrict the nature and range ofseverity of disorders that will be accessibleto investigators based solely in traditionalacadell1ic settings. These constraints willnecessarily reduce the breadth of researchquestions that can be addressed. Questionsthat require the full range of variability andheterogeneity of a particular disorder wouldbe more difficult to address in the academicenvironment. Workshop participants notedthat the most immediate solution to this, thepooling of patient populations from differ­ent settings, introduces site variance thatmay be confounded with severity and othervariables. This phenomenon could signifi­cantly compromise the integrity of the studydesign.

Vertical integration of health service de­livery olay increase difficulty in problems ofaccess to ethnic minority populations. Con­solidation of hospitals and creation of pri­mary care networks are largely based oneconomic considerations of potential effi­ciencies in care. Participants were con­cerned that clinicians with practices that arenot considered cost-effective by a centralcorporate entity would be excluded fromnetworks. Patients who require extensivecare, close monitoring for compliance, andfrequent follow-up are not attractive to pay­ors with fixed budgets. Certain kinds ofpatients (poor, traditionally medically un­derserved, seriously mentally ill substanceabusers) and the clinicians who serve themmay not be invited to participate. This limi­tation could severely restrict the diversityand variability of patient populations avail­able for clinical investigation in an academichealth center that is part of a managed care

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Clinical Research in Managed Care

system. The historically black medicalschools and other health care institutionsthat serve predominantly minority popula­tions constitute a potentially significantresource for clinical research with ethnicminority patients and populations. Theseinstitutions may be particularly disadvan­taged with regard to the development ofresearch because they have not had thesupport to develop the scientific infrastruc­ture and private sources of funds that areessential to a major research program.

Workshop participants identified anumber of other barriers to clinical researchemerging in the transition toward healthcare reform. A number of investigatorsnoted that inpatient psychiatric units havebecome less useful research resources:length of stay has been significantly short­ened, and many procedures and conditionsonce carried out or managed in the inpa­tient setting have been moved to the outpa­tient setting. This change has alreadyresulted in a number of modifications toestablished scientific procedures. For exam­ple) a fundamental tenet of design is that thesymptoms of disease must be differentiatedfrom the effects of treatment. The result hasbeen development of a number of proce­dures such as drug washout) placebo mn­in, and other approaches to isolate the truedisease state. Particularly for patients withsevere mental disorders, all of these ap­proaches are best conducted in a morecontrolled environment such as an inpatientsetting, with expenses that are increasinglyimpossible to reimburse.

Much clinical research in psychophar­macology involves the theory-driven searchfor new indications for use of marketedcompounds (the 50-called off-label indica­tions). Examples include the use of anticon­vulsants to manage bipolar illness and theuse of stimulants to treat depression associ­ated with chronic disease. Health insuranceplans that have prescription benefits gener­ally provide reimbursement for only partic­ular medications in a listing referred to as aformulary. For a treatment not listed in the

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formula!)', co-payments or total out-of­pocket payment by the patient or investiga­tor are required. Clinical trials in nursinghomes are further constrained by regula­tions derived from the nursing home reformprovisions of OBRA '87 restricting the type)use, indication, dose, and duration of psy­chotropic medication.

EMERGING OPPORTUNITIESFOR NEW APPROACHES

Workshop participants concurred that thefuture organization of health care serviceswill create significant opportunities for re­search in the mental disorders of late life.Mental health services research will gaineven greater prominence as these new ar­rangements are developed, and studies ofaccess, cost, cost-offset, and outcome areemphasized. Outcomes of interest extendfar beyond the traditional focus on symp..toms of psychopathology, to incorporatemeasures of function, disability, and qualityof life.

A number of interesting clinical re­search opportunities will also evolve. Forexample, studies of treatment-refractory ill­ness have been compromised by concernsregarding the adequacy of prior treatmenttrials. Managed care and compulsory treat­ment guidelines will increase the likelihoodof full trials of specific treatments. Followingsuch guidelines may improve the homoge­neity of patient samples with truly refractol)'illness who are seen in academic settings.

Clinical research frequently involves in­tensive study of individual differences byexamining rich and varied databases onvery small) non-representative populations.In the new health care system, we may haveexactly the opposite situation. Health caremanagement requires thinner databases, onlarger samples, from populations withknown parameters. This may providegreater opportunity for generalization andfor generating and testing new hypotheses.

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Participants agreed that exciting possibilitiesfor longitudinal studies will be created bythe development of advanced informationsystems describing populations and theirhealth care.

Health care management databases willrepresent the characteristics of a more het­erogeneous population than available inmost clinical research. Workshop partici­pants saw this as an opportunity for furtherstudy of the impact of medical burden onthe course and outcome of mental disorderin late life, and, conversely, on the impactof mental illness on the course and outcomeof physical disorders.

Finally, the emphasis of managedhealth care systems on the continuity of careand the coordination of multiple servicesites was seen as validating the need fordiversification of research sites that has be­come a tradition in geriatrics.

CONCLUSION

The development of systems of managedhealth care and the processes leading tohealth care reform put great pressure onclinical research in the late-life mental dis­orders. Established practices of clinical care,and of the research associated with it) arebeing reformulated. The basic questions ofclinical research-studies of phenomenol­ogy, etiology, and pathogenesis; diagnosis;and clinical course, treatment response, out­come, and prevention--can no longer beaddressed with research designs and meth­ods that were developed on the academic

Lebowitz and Gottlieb

health system of the last generation. How­ever, exciting opportunities are emerging tostudy broad, heterogeneous populationsand to focus on a diversity of outcomes.Geriatrics, with its history of longitudinalresearch, attention to comorbidity, breadthof interest in function and disability, andaccess to nonpsychiatric settings, such asnursing homes, is in an ideal position tocapitalize on these opportunities and to leadthe mental health field into this new era.

This report is the result ofa workshop, ItClin­icalResearch in the Managed Care Environ­ment," held on April 25, 1994, andsponsored by the Mental Disorders of theAging Research Branch of the National In­stitute of Mental Health (NIMH). Gary L.Gottlieb, M.D., M.B.A., and Barry D.Lebowitz, Ph.D., chaired the workshop. Theworkshop included the following partici-pants from the field.· Nathan Billig, M.D.,.WalterP. Bland, M.D.; GeneD. Cohen, M.D.,Ph.D.,' jiska Cohen-Mansfield, Ph.D.,'Davangere P. Devanand, M.D.; Ira R. Katz,M.D., Ph.D.; Alan G. Kraut, Ph.D.,· WilliamB. Lawson, M.D., Ph.D.,' Harold A. Pincus,M.D.; Peter v: Rabins, M.D.,· Jules Rosen,M.D.; andSteven S. Shaifstein, M.D.; andthefollowing participantsfrom the National In-stitutes of Health: Rex w: Cowdry, M.D.;HarrietL.G. Gordon, M.D.; RickA.Martinez,M.D.; George Niederehe, Ph.D.;Jean K. Pad­dock, Ph.D.; Jane L. Pearson, Ph.D.,. andjaneA. Steinberg, Ph.D. Staffsupportfortheworkshop was provided by Barbara Taylor,ofCircle Solution, Inc., andFaye K. Vlahos,afNIMH.

References

1. Marshall E: Academic medicine's stake in healthcare reform. Science 1994; 263:1081

2. Depression Guidelines Panel: Depression in Pri­mary Care, Vol. 2: Treatment of Major Depression.Clinical Practice Guideline Number 5. Rockville,

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MD. U.S. Department of Health and Human Ser­vices t Public Health Service, Agency for HealthCare Policy and Research. AHCPR Publication No.93-0551, April 1993

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