Advertisement

Recognition and Resolution of Ethical Barriers to Palliative Care Research

  • Sarah Gebauer
  • Perry Fine
Chapter

Abstract

Palliative care research can be defined as research related to understanding and improving the quality of life of patients near the end of life. There is a paucity of research in this field for two overarching reasons. Medical interest related to relieving burden of illness is relatively new, and patients nearing the end of life have either been marginalized (i.e., viewed as not worthy of “investment” of scarce research dollars) or viewed as too vulnerable to undergo the rigorous processes of formalized research. Concerns about such vulnerabilities have created an ethical paradox. In order to protect this patient population from potential harms, including coercion, exploitation, and the possibility of imposing additional suffering at the end of life, terminally ill patients have been deprived of the opportunity to participate in research afforded to other patient populations: the frank withholding of an ethical prerogative. As a result, innovation and empirical developments in the field have been seriously curtailed.

This chapter will explicate these barriers and misconceptions and address the ways in which research can and should proceed, following normative ethical imperatives. Patients with far-advanced medical illness provide a good paradigm to explore ethical concerns about vulnerable populations insofar as they embody some of the greatest challenges to unencumbered decision-making: a high symptom burden (including fatigue, pain, mood disturbance, nausea, dyspnea), cognitive impairment, and imminent mortality. As such, the tenets brought forth in this chapter may pertain to barriers to, and the provision of, ethical research in other vulnerable populations.

References

  1. Abernethy, A. P., Capell, W. H., Aziz, N. M., Ritchie, C., Prince-Paul, M., Bennett, R. E., & Kutner, J. S. (2014). Ethical conduct of palliative care research: Enhancing communication between investigators and institutional review boards. Journal of Pain and Symptom Management, 48(6), 1211–1221.  https://doi.org/10.1016/j.jpainsymman.2014.05.005.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Agar, M., Ko, D. N., Sheehan, C., Chapman, M., & Currow, D. C. (2013). Informed consent in palliative care clinical trials: Challenging but possible. Journal of Palliative Medicine, 16(5), 485–491.  https://doi.org/10.1089/jpm.2012.0422.CrossRefPubMedGoogle Scholar
  3. Agrawal, M. (2003). Voluntariness in clinical research at the end of life. Journal of Pain and Symptom Management, 25(4), S25–S32.CrossRefGoogle Scholar
  4. Appelbaum, P. S., Lidz, C. W., & Klitzman, R. (2009). Voluntariness of consent to research: A preliminary empirical investigation. IRB, 31(6), 10–14.PubMedGoogle Scholar
  5. Berg, J. W., Appelbaum, P. S., & ebrary Inc. (2001). Informed consent legal theory and clinical practice (pp. xii, 340 p.). Retrieved from http://site.ebrary.com/lib/yale/Doc?id=10375104
  6. Brechtl, J. R., Murshed, S., Homel, P., & Bookbinder, M. (2006). Monitoring symptoms in patients with advanced illness in long-term care: A pilot study. Journal of Pain and Symptom Management, 32(2), 168–74.Google Scholar
  7. Bingel, U., Lorenz, J., Schoell, E., Weiller, C., & Buchel, C. (2006). Mechanisms of placebo analgesia: rACC recruitment of a subcortical antinociceptive network. Pain, 120(1–2), 8–15.  https://doi.org/10.1016/j.pain.2005.08.027.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Casarett, D. J. (2003). Assessing decision-making capacity in the setting of palliative care research. Journal of Pain and Symptom Management, 25(4), S6–S13.CrossRefGoogle Scholar
  9. Casarett, D. (2005). Ethical considerations in end-of-life care and research. Journal of Palliative Medicine, 8(Suppl 1), S148–S160.  https://doi.org/10.1089/jpm.2005.8.s-148.CrossRefPubMedGoogle Scholar
  10. Covarrubias-Gomez, A., Hernandez-Martinez, E. E., Ruiz-Ramirez, S., & Lopez Collada-Estrada, M. (2014). Assessment of pain and other symptoms in Mexican patients with advanced illness. Journal of Pain & Palliative Care Pharmacotherapy, 28(4), 394–398.  https://doi.org/10.3109/15360288.2014.959235.CrossRefGoogle Scholar
  11. Eippert, F., Bingel, U., Schoell, E. D., Yacubian, J., Klinger, R., Lorenz, J., & Buchel, C. (2009). Activation of the opioidergic descending pain control system underlies placebo analgesia. Neuron, 63(4), 533–543.  https://doi.org/10.1016/j.neuron.2009.07.014.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Emanuel, E. J., & Miller, F. G. (2001). The ethics of placebo-controlled trials–a middle ground. The New England Journal of Medicine, 345(12), 915–919.  https://doi.org/10.1056/NEJM200109203451211.CrossRefPubMedGoogle Scholar
  13. Emanuel, E. J., Wendler, D., & Grady, C. (2000). What makes clinical research ethical? JAMA, 283(20), 2701–2711.CrossRefGoogle Scholar
  14. Enserink, M. (2000). Bioethics. Helsinki's new clinical rules: Fewer placebos, more disclosure. Science, 290(5491), 418–419.CrossRefGoogle Scholar
  15. Field, M. J., Cassel, C. K., & Institute of Medicine (U.S.). Committee on Care at the End of Life. (1997). Approaching death: Improving care at the end of life. Washington, DC: National Academy Press.Google Scholar
  16. Fine, P. G. (2003). Maximizing benefits and minimizing risks in palliative care research that involves patients near the end of life. Journal of Pain and Symptom Management, 25(4), S53–S62.CrossRefGoogle Scholar
  17. Fine, P. G., & Peterson, D. (2002). Caring about what dying patients care about caring. Journal of Pain and Symptom Management, 23(4), 267–268.CrossRefGoogle Scholar
  18. Fine, P. G., Roberts, W. J., Gillette, R. G., & Child, T. R. (1994). Slowly developing placebo responses confound tests of intravenous phentolamine to determine mechanisms underlying idiopathic chronic low back pain. Pain, 56(2), 235–242.CrossRefGoogle Scholar
  19. Foley, K., & Gelband, H. (2001). Improving Palliative Care for Cancer, National Cancer Policy Board, National Research Council. National Academy of Sciences, 10.Google Scholar
  20. Gamondi, C., Galli, N., Schonholzer, C., Marone, C., Zwahlen, H., Gabutti, L., et al. (2013). Frequency and severity of pain and symptom distress among patients with chronic kidney disease receiving dialysis. Swiss Medical Weekly, 143, w13750.  https://doi.org/10.4414/smw.2013.13750.CrossRefPubMedGoogle Scholar
  21. Grant, M., Elk, R., Ferrell, B., Morrison, R. S., & von Gunten, C. F. (2009). Current status of palliative care–clinical implementation, education, and research. CA: a Cancer Journal for Clinicians, 59(5), 327–335.  https://doi.org/10.3322/caac.20032.CrossRefGoogle Scholar
  22. Hickman, S. E., Cartwright, J. C., Nelson, C. A., & Knafl, K. (2012). Compassion and vigilance: investigators’ strategies to manage ethical concerns in palliative and end-of-life research. Journal of Palliative Medicine, 15(8), 880–889.  https://doi.org/10.1089/jpm.2011.0515.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Johnson, K. S. (2013). Racial and ethnic disparities in palliative care. Journal of Palliative Medicine, 16(11), 1329–1334.  https://doi.org/10.1089/jpm.2013.9468.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Karlawish, J. H. (2003). Conducting research that involves subjects at the end of life who are unable to give consent. Journal of Pain and Symptom Management, 25(4), S14–S24.CrossRefGoogle Scholar
  25. Kars, M. C., van Thiel, G. J., van der Graaf, R., Moors, M., de Graeff, A., & van Delden, J. J. (2016). A systematic review of reasons for gatekeeping in palliative care research. Palliative Medicine, 30(6), 533–548.  https://doi.org/10.1177/0269216315616759.CrossRefPubMedGoogle Scholar
  26. Kirchhoff, K. T., & Kehl, K. A. (2007). Recruiting participants in end-of-life research. The American Journal of Hospice & Palliative Care, 24(6), 515–521.  https://doi.org/10.1177/1049909107300551.CrossRefGoogle Scholar
  27. Kolva, E., Rosenfeld, B., Brescia, R., & Comfort, C. (2014). Assessing decision-making capacity at end of life. General Hospital Psychiatry, 36(4), 392–397.  https://doi.org/10.1016/j.genhosppsych.2014.02.013.CrossRefPubMedGoogle Scholar
  28. Mackin, M. L., Herr, K., Bergen-Jackson, K., Fine, P., Forcucci, C., & Sanders, S. (2009). Research participation by older adults at end of life: barriers and solutions. Research in Gerontological Nursing, 2(3), 162–171.  https://doi.org/10.3928/19404921-20090421-05.CrossRefPubMedPubMedCentralGoogle Scholar
  29. Nelson, R. M., & Merz, J. F. (2002). Voluntariness of consent for research: An empirical and conceptual review. Medical Care, 40(9 Suppl), V69–V80. https:// doi.org/10.1097/01.MLR.0000023958.28108.9C.CrossRefPubMedGoogle Scholar
  30. Nuremberg Military, T. (1996). The nuremberg code. JAMA, 276(20), 1691.CrossRefGoogle Scholar
  31. Pantilat, S. Z., O'Riordan, D. L., Rathfon, M. A., Dracup, K. A., & De Marco, T. (2016). Etiology of pain and its association with quality of life among patients with heart failure. Journal of Palliative Medicine.  https://doi.org/10.1089/jpm.2016.0095.CrossRefGoogle Scholar
  32. Petrovic, P., Kalso, E., Petersson, K. M., Andersson, J., Fransson, P., & Ingvar, M. (2010). A prefrontal non-opioid mechanism in placebo analgesia. Pain, 150(1), 59–65.  https://doi.org/10.1016/j.pain.2010.03.011.CrossRefPubMedGoogle Scholar
  33. Pollo, A., & Benedetti, F. (2013). Pain and the placebo/nocebo effect. In R. J. Moore (Ed.), Handbook of pain and palliative care. New York: Springer.Google Scholar
  34. Protection of Human Subjects. (2009). Retrieved from http://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/
  35. Romem, A., Tom, S. E., Beauchene, M., Babington, L., Scharf, S. M., & Romem, A. (2015). Pain management at the end of life: A comparative study of cancer, dementia, and chronic obstructive pulmonary disease patients. Palliative Medicine, 29(5), 464–469.  https://doi.org/10.1177/0269216315570411.CrossRefPubMedGoogle Scholar
  36. Seow, H., Barbera, L., Sutradhar, R., Howell, D., Dudgeon, D., Atzema, C., et al. (2013). Trajectory of performance status and symptom scores for patients with cancer during the last six months of life. Journal of Clinical Oncology, 29(9), 1151–1158.  https://doi.org/10.1200/JCO.2010.30.7173.CrossRefGoogle Scholar
  37. Stone, P. C., Gwilliam, B., Keeley, V., Todd, C., Kelly, L. C., & Barclay, S. (2013). Factors affecting recruitment to an observational multicentre palliative care study. BMJ Supportive & Palliative Care, 3(3), 318–323.  https://doi.org/10.1136/bmjspcare-2012-000396.CrossRefGoogle Scholar
  38. Temple, R., & Ellenberg, S. S. (2000). Placebo-controlled trials and active-control trials in the evaluation of new treatments. Part 1: Ethical and scientific issues. Annals of Internal Medicine, 133(6), 455–463.CrossRefGoogle Scholar
  39. Todd, A. M., Laird, B. J., Boyle, D., Boyd, A. C., Colvin, L. A., & Fallon, M. T. (2009). A systematic review examining the literature on attitudes of patients with advanced cancer toward research. Journal of Pain and Symptom Management, 37(6), 1078–1085.  https://doi.org/10.1016/j.jpainsymman.2008.07.009.CrossRefPubMedGoogle Scholar
  40. Vase, L., Riley, J. L., 3rd, & Price, D. D. (2002). A comparison of placebo effects in clinical analgesic trials versus studies of placebo analgesia. Pain, 99(3), 443–452.CrossRefGoogle Scholar
  41. Wendler, D., & Miller, F. G. (2007). Assessing research risks systematically: The net risks test. Journal of Medical Ethics, 33(8), 481–486.  https://doi.org/10.1136/jme.2005.014043.CrossRefPubMedPubMedCentralGoogle Scholar
  42. White, C., & Hardy, J. (2010). What do palliative care patients and their relatives think about research in palliative care? – A systematic review. Support Care Cancer, 18(8), 905–911.  https://doi.org/10.1007/s00520-009-0724-1.CrossRefPubMedGoogle Scholar
  43. White, C., Gilshenan, K., & Hardy, J. (2008). A survey of the views of palliative care healthcare professionals towards referring cancer patients to participate in randomized controlled trials in palliative care. Support Care Cancer, 16(12), 1397–1405.  https://doi.org/10.1007/s00520-008-0441-1.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Sarah Gebauer
    • 1
  • Perry Fine
    • 2
  1. 1.Department of AnesthesiologyUniversity of New MexicoAlbuquerqueUSA
  2. 2.Department of AnesthesiologyUniversity of UtahSalt Lake CityUSA

Personalised recommendations