Advising AIDS Patients WhoParticipate in Clinical Trials

By Frank DeLeon-Jones, M.D.,Allen D. Allen, Ph.D., andDiane Chriss, L.C.S.W.

Abstract

Many individuals infected withHIV are offered an opportunityto participate in clinical trials on

investigational therapies. The duty to avoidcreating unrealistic expectations for suchpatients is important, both as a matter ofmedical ethics and for purposes of main-taining credibility. This duty often conflictswith the need to offer HIV-infectedpatients hope and to support their psycho-logical well-being. We offer some recom-mendations that evolved in the setting of acounty hospital with a busy AIDS pro-gram.

IntroductionThe diagnosis of HIV infection is a psy-

chological Stressor that can result in reac-tive depression and anxiety, conserva-tion-withdrawal, and/or cognitivechanges.1,2 Moulton et al.3 report that thesigns and symptoms of HIV infection aremore apt to produce feelings of hopeless-ness than mere knowledge of an HIV-pos-itive status. In addition to impairing qual-ity of life, these feelings may exacerbatethe progression of HIV disease.4 Evenwhen knowledge of HIV infection doesnot result in a frank psychopathologicreaction, it may lead a patient to consider'rational suicide' as a solution to the prob-

lem.5 For these reasons, most health careprofessionals emphasize the positive forpatients with early HIV disease or asymp-tomatic infection. The patients are toldthat medical intervention can providethem with a good quality of life for manyyears. In the meantime, the state of the artmight advance to the point where HIV-infected individuals can anticipate a near-normal life expectancy.The problem of counseling HIV-infect-

ed patients presents a greater ethicaldilemma when it comes to human subjectsparticipating in clinical trials on investiga-tional HIV therapies. Following elabora-tion of the Nuremberg Declaration afterWorld War II, the Helsinki Declarations Iand II were adopted by the World Medi-cal Association to protect human subjectsused in medical experimentation.67Although the Helsinki Declarations aresometimes considered intrusive for thephysician-patient relationship,6-8 few civi-lized nations today would repeat theTuskegee syphilis study, which continuesto generate suspicion of medicalresearchers among HIV-positive blackmales.9 Rather, it is widely accepted thatinformed consent is a necessary prerequi-site for human experimentation.Informed consent for participation in a

therapeutic trial must include enumera-tion of the potential benefits for patientswho participate. Unfortunately, potentialbenefits for the subjects in a therapeutictrial on a new AIDS treatment cannot befully and fairly explained unless thestudy patients know that the proventreatments for HIV infection may not belife-saving. Private physicians who refer

patients to such studies often explain thatgetting into the right study is an HIV-infected patient's best hope of delaying anultimately grave prognosis. On the otherhand, it must be emphasized that investi-gational therapies offer no proven benefit,and patients should not enter a drug trialwith the expectation that they will beguaranteed a benefit by participating;otherwise, patients may become disap-pointed with study physicians due tounrealistic expectations.10-11 Such candiddisclosures necessarily carry a messagethat HIV disease is fatal and incurable. Asa result, the need to obtain informed con-sent has to be balanced against the risk ofpulling the rug out from under a patient'spsychological defenses. In order to strikesuch a balance, we propose the followingguidelines, which evolved in the settingof a county hospital that provides prima-ry care for hundreds of HIV-infectedpatients and is the site for a wide varietyof therapeutic trials on investigationaltherapies for HIV infection and its com-plications.

Psychological Status as Part of theStudy Inclusion Criteria

Because some patients may harborheightened expectations for the success ofa given investigational therapy, it isimportant to assess patient reality testingat the onset of the study. Initial assess-ment provides the opportunity to deter-mine whether a patient is appropriate forstudy inclusion or whether psychologicalcounseling would be advisable because ofa heightened state of fear about disease

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It is important to assess patient realitytesting at the onset of the study.

outcome, manifested as unrealistic expec-tations for the success of extant therapiesor of investigational protocols.

Full Explanation ofResearch Rationale

The motive to participate in an investi-gational drug trial for most individuals isboth altruistic, in terms of increasing sci-entific knowledge that might benefit oth-ers, as well as egocentric, in terms ofacquiring benefits for their own medicalcondition. The scientific and/or clinicalrationale for a study should be disclosedas fully as possible to patients who havesatisfied the inclusion criteria. This willfoster trust in the study physicians andhelp maintain realistic hope in the patient.

Truthful Explanation ofTherapeutic Alternatives

Hope is an important therapeutic aidthat should be available to both patientsand physicians. A full explanation of thetherapeutic alternatives in a sincere andtruthful manner can contribute to foster-ing and preserving hope in the patient.HIV-infected individuals deserve to knowand should be told the truth about thesafety and efficacy of all available thera-peutic modalities, including investiga-tional therapies. Patients should be madeaware of all maneuvers and interventionsthat can delay disease progression andhave a potential for extending life.

Allowing the Patient to Set theAgenda for Prognostic DisclosureSome patients prefer to know even dif-ficult truths and sincerely request toknow their human immunodeficiencyvirus prognosis. Others may be psycho-logically traumatized by the physician'sexpression of a negative prognosis andmay prefer to remain in a protective stateof denial. Often, patients belonging to theformer category will request candid dis-

closure by asking, "Tell me the truth, Doc;I can take it! What do you really think aremy chances?" In the absence of such anexplicit request, physicians should notvolunteer pessimistic opinions. Oneshould remember that the data obtainedfrom a large, prospective, randomized,controlled study only tell us what toexpect across a large population ofpatients. The data make no predictions ofoutcome for any one individual subject.In individual cases, the empathy of physi-cians toward the HIV-positive patient willhelp address the concerns and expecta-tions of that patient with regard to theefficacy of approved or investigationaltherapies. The anxiety of physicians overimparting negative information should bedealt with off-line so as not to unfairlyburden the patient with the physician'sanxiety.

Psychological Counseling forStaff Members Who Suffer from

'AIDS Burnout'

Hospital and clinic staff members whofrequently encounter AIDS patients arecontinually reminded of the limitationsof clinical medicine, the frailty of humanlife, and their own vulnerability. This canlead to a reactive or existential mood dis-order characterized by dysphoria, anxi-ety, and /or irritability, and referred to as'AIDS burnout.' Psychological counselingshould be readily available for personnelwho experience this reaction, both forhumanitarian reasons and to preservehuman assets. Patient contact should beavoided until the affected person's cop-ing mechanisms have been restored totheir premorbid level of functioning orbetter. D

References1. Polk-Walker, G.C. Treatment of AIDS in apsychiatric setting. Perspect Psychiatr Care25:9-13,1989.

2. Quill, T.E., Townsend, P. Bad news: Deliv-ery, dialogue, and dilemmas. Arch Intern Med151:463-468,1991.3. Moulton, J.M., Stempel, R.R., Bacchetti, P.,Temoshok, L., Moss, A.R. Results of a one yearlongitudinal study of HIV antibody test notifi-cation from the San Francisco General Hospitalcohort. / Acquir Immune Defie Syndr 4:787-794,1991.4. Cohen, S.I. Voodoo death, the stressresponse, and AIDS. In: Costa, E., Greengard,P. (Eds.), Psychological, Neuropsychiatrie, andSubstance Abuse Aspects of AIDS. New York:Raven Press, pp. 95-109,1988.5. Karlinsky, H., Taerk, G., Schwartz, K., Ennis,]., Rodin, G. Suicide attempts and resuscitationdilemmas. Gen Hosp Psych 10:423^130,1988.6. Jensen, A.B. Det informerede samtykke. His-torisk baggrund og nutidige problemer. UgeskrLaeger 152:3591-3593,1990.7. Belsey, A. Patients, doctors and experimenta-tion: Doubts about the Declaration of Helsinki.¡Med Ethics 4:182-185,1978.8. Taylor, K.M., Keiner, M. Informed consent:The physician's perspective. Soc Sei Med24:135-143,1987.9. Thomas, S.B., Quinn, S.C. The Tuskegeesyphilis study, 1932 to 1972: Implications forHIV education and AIDS risk education pro-grams in the Black community. Am J PublicHealth 81:1498-1505,1991.10. Bergler, J.H., Pennington, A.C., Metcalfe,M., Freis, E.D. Informed consent: How muchdoes the patient understand? Clin PharmacolTher 27:435^40,1980.11. Penman, D.T., Holland, J.C., Bahna, CF., etal. Informed consent for investigationalchemotherapy: Patients' and physicians' per-ceptions. / Clin Oncol 2:849-855,1984.

Dr. DeLeon-Jones is Chief, Department of Psy-chiatry, Olive View-UCLA Medical Center,Sylmar, CA; Dr. Allen is Chair, Medical Deci-sion Making, IEEE Systems, Man, and Cyber-netics Society; Ms. Chriss is in private practicein Westlake Village, CA.

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