© 2003 U.S. Cancer Pain Relief Committee 0885-3924/03/$–see front matterPublished by Elsevier. All rights reserved. doi:10.1016/S0885-3924(03)00058-7

Vol. 25 No. 4 April 2003 Journal of Pain and Symptom Management S3

Preface

Ethical Challenges of Palliative Care Research

David J. Casarett, MD, MA, Ann Knebel, PhD, and Karin Helmers, PhD

Center for Health Equity Research and Promotion (D.J.C.), Philadelphia Veterans Administration Medical Center, and Division of Geriatrics (D.J.C.), University of Pennsylvania, Philadelphia, Pennsylvania; and National Institute of Nursing Research (A.K., K.H.), Department of

Health and Human Services, National Institutes of Health, Bethesda, Maryland, USA

Recent years have seen a dramatic increasein palliative care research, broadly defined asresearch related to understanding and improv-ing the quality of life of patients near the endof life. This new field of research has produceda variety of ethical concerns for investigators,clinicians, hospices, and Institutional ReviewBoards (IRBs).

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Broadly, these concerns canbe divided into concerns about the informedconsent process and concerns about the risks,potential benefits, and burdens that are cre-ated by a study’s design.

At the heart of all of these concerns is thequestion of whether palliative care researchcreates ethical challenges that are new, orwhich are unique to this field. The answer tothis question will have important implicationsfor the design and conduct of palliative care re-search. If palliative care research does, in fact,raise unique ethical issues, then special restric-tions, protections, and guidelines should beconsidered. If it does not, then the strategiesdevised by investigators in other fields will suf-fice to protect subjects and special guidelinesare not necessary. In that case, any guidelinesthat are established for palliative care researchshould consist largely of recommendations im-ported from other fields.

This workshop was convened in order to de-fine ethical aspects of palliative care researchthat are unique, or different than, other kindsof research involving different populations,and which warrant special guidelines, proce-

dures, or restrictions. This workshop broughttogether researchers and clinicians familiar withthe ethical challenges of palliative care research,listed on a following page. Held on the NationalInstitutes of Health campus on September 12and 13, 2002, this conference was co-sponsoredby the National Institute of Nursing Research(NINR) and the Office of Rare Diseases(ORD). In addition, generous support for pub-lication and dissemination was provided by aPresidential Award from the Greenwall Foun-dation.

The articles that follow this introduction werethe focus of heated discussion and debate overthe two-day conference, with critical input andrevisions suggested by the workshop partici-pants. Throughout the workshop, several keypoints emerged that are summarized below. Al-though it would be incorrect to claim thatthese points represent an absolute consensusof the workshop participants, they do, how-ever, represent ideas and positions that mostparticipants were willing to support.

Ethical Challenges Related to Informed Consent in Palliative Care Research: Key Points

1. Additional scrutiny of informed consentfor palliative care research should notcome at the cost of decreased attention toresearch that involves other populationsthat may be equally vulnerable. Informedconsent deserves close scrutiny in all clini-cal research, not only research that in-volves patients near the end of life.

Address reprint requests to:

David J. Casarett, MD, Uni-versity of Pennsylvania, 3615 Chestnut Street, Phila-delphia, PA 19104, USA.

S4 Casarett et al. Vol. 25 No. 4 April 2003

2. This population is heterogeneous with re-spect to prospective subjects’ ability togive voluntary consent to research partici-pation. Patients near the end of life arenot inherently less able to give voluntaryconsent to palliative care research thanare other patient populations. Instead, as-sessments of voluntariness should be basedon patient characteristics, patients’ rela-tionships with study representatives, andthe institutional setting, just as they arefor other forms of research.

3. This population is also diverse with respectto decision-making capacity, and blanketprescriptions about safeguards and assess-ments of capacity are not useful. Instead,additional assessments of capacity shouldbe based on patient population character-istics, and the balance of risks and poten-tial benefits posed by a study.

4. Because of the rapid time course of manyterminal illnesses, and fluctuations incognitive status, palliative care researchoffers a good setting for the use of ad-vance consent. This is particularly truewhen studies pose greater than minimalrisks, when they do not offer potentialbenefits, or both. When advance consentis employed, reconsent is important inthe event that subjects regain capacity.

5. For some studies in which increasing cog-nitive impairment is likely, the consentprocess may include a discussion of a pa-tient’s willingness to continue participa-tion if capacity is lost.

Designing Palliative Care Research That Maximizes Potential Benefitsand Minimizes Risks and Burdens:Key Points

1. Institutional Review Boards that frequentlyreview palliative care research should in-clude members who are familiar with thecare of patients near the end of life andwho can assess the risks, potential bene-fits, and value of proposed research.

2. Regardless of the study design used to as-sess the efficacy of symptom interventionstrategies, it is essential that investigators

provide adequate “breakthrough” or “res-cue” therapy and that they measure “res-cue” endpoints as accurately as possible.

3. It is not necessary that investigators in-form prospective subjects that they arebelieved to be near the end of life, eitherin the consent process or throughoutdata collection. This omission should notbe considered “deception” that requiresadditional IRB review and oversight.

4. The sensitive nature of certain kinds ofdata collected in the course of palliativecare research, particularly data regardingassisted suicide, may warrant certificatesof confidentiality from the Department ofHealth and Human Services.

5. In general, interviews of patients near theend of life and bereaved family membersneed not cause significant distress, andare often valued by subjects. Studies thatemploy interviews with these groups shouldnot necessarily be subjected to additionalscrutiny or restrictions but should insteademploy mechanisms to assess and man-age distress if it occurs.

6. There are insufficient data to make recom-mendations about appropriate and inap-propriate timing of recruitment and datacollection from bereaved family members.However, most participants felt that thetime frame that is currently used for moststudies (1 to 3 months) is acceptable.

7. Quality Improvement activities are essen-tial in improving the care of patients nearthe end of life. Efforts to protect therights and welfare of patients involved inthese activities should balance the needfor protections against the ethical imper-ative to improve care.

Conclusion

Research on issues at the end of life is rap-idly growing, and its importance increases asour population ages. There is an urgent needto find better ways to improve pain and symp-tom management at the end of life, to helppeople die with dignity, and to comfort the be-reaved. Although this research is important, itis not without ethical challenges. Therefore,efforts to improve the standard of palliative

Vol. 25 No. 4 April 2003 Ethical Challenges of Palliative Care Research S5

care through research and through quality im-provement activities must be sensitive to ethi-cal concerns.

In summary, conference participants agreedthat the ethical issues raised by palliative careresearch are, for the most part, not unique tothis field. The principles of ethical researchconduct that guide other forms of research canand should be applied to this field.

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For in-stance, the consent process should be carefuland thoughtful, with adequate attention givenboth to an individual’s decision-making capac-ity and the voluntariness of his or her decision.Similarly, investigators should pay close atten-tion to a study’s design, to ensure that it offersan optimal balance of risks, burdens and po-tential benefits.

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Finally, as with any research, astudy is only ethically sound if its risks are rea-sonable in proportion to its potential benefits,and the knowledge to be gained. Thus, pallia-tive care researchers, like researchers in otherfields, must demonstrate that their researchquestions are important, their methods are ap-propriate to produce valid results, and thattheir findings will be generalizable.

Acknowledgments

The conference co-chairs, David Casarett,MD, MA, Ann Knebel, PhD, and Karin Helm-ers, PhD, gratefully acknowledge financial sup-port from the National Institute of Nursing Re-search, the Office of Rare Diseases, and fromthe Greenwall Foundation, as well as the en-thusiastic discussion and debate among theconference participants:

Manish Agrawal, MDGloria Bonner, PhD, RNMiriam E. Cameron, PhD, RN, MSGrace H. Christ, DSWStephen Connor, PhDBarbara J. Daly, PhD, RN, FAAN

Evan G. DeRenzo, PhDJacqueline Dunbar-Jacob, PhD, RN, FAANPerry G. Fine, MDChristine Grady, PhD, RN, FAANDavid Introcaso, PhDJason Karlawish, MDBarbara A. Koenig, PhD, RNPatrick McNeilly, PhDMarie T. Nolan, DNSc, RNMarian Secundy, PhDJames A. Tulsky, MDDave Wendler, PhD

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