Abstract

The palliative care field is experiencing substantive growth in clinical trial-based research. Randomized controlled trials provide the necessary rigor and conditions for assessing a treatment’s efficacy in a controlled population. It is therefore important that a trial is meticulously designed from the outset to ensure the integrity of the ultimate results. In this article, our team discusses ten tips on clinical trial design drawn from collective experiences in the field. These ten tips cover a range of topics that can prove challenging in trial design, from developing initial methodologies to planning sample size and powering the trial, as well as collaboratively navigating the ethical issues of trial initiation and implementation as a cohesive team. We aim to help new researchers design sound trials and continue to grow the evidence base for our specialty. The guidance provided here can be used independently or in addition to the ten tips provided by this team in a separate article focused on what palliative care clinicians should know about interpreting a clinical trial.

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References

1. O’Cathain A, Thomas KJ, Drabble SJ, et al. What can qualitative research do for randomised controlled trials? A systematic mapping review. BMJ Open 2013;3(6):e002889;
2. Donovan J, Mills N, Smith M, et al. Quality improvement report: Improving design and conduct of randomised trials by embedding them in qualitative research: ProtecT (prostate testing for cancer and treatment) study. Commentary: Presenting unbiased information to patients can be difficult. BMJ 2002;325(7367):766–770;
3. Olson RE, Smith A, Huggett G, et al. Using a qualitative sub-study to inform the design and delivery of randomised controlled trials on medicinal cannabis for symptom relief in patients with advanced cancer. Trials 2022;23(1):752;
4. Jordhoy MS, Kaasa S, Fayers P, et al. Challenges in palliative care research; recruitment, attrition and compliance: Experience from a randomized controlled trial. Palliat Med 1999;13(4):299–310;
5. Parker RA, Weir CJ. Multiple secondary outcome analyses: Precise interpretation is important. Trials 2022;23(1):27;
6. Agar M, Luckett T. Outcome measures for palliative care research. Curr Opin Support Palliat Care 2012;6(4):500–507;
7. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67(6):361–370;
8. Luckett T, King MT. Choosing patient-reported outcome measures for cancer clinical research–practical principles and an algorithm to assist non-specialist researchers. Eur J Cancer 2010;46(18):3149–3157;
9. Peterson SJ, Foley S. Clinician’s guide to understanding effect size, Alpha level, Power, and sample size. Nutr Clin Pract 2021;36(3):598–605;
10. Currow DC, Wheeler JL, Glare PA, et al. A framework for generalizability in palliative care. J Pain Symptom Manage 2009;37(3):373–386;
11. Currow DC, Tieman JJ, Greene A, et al. Refining a checklist for reporting patient populations and service characteristics in hospice and palliative care research. J Pain Symptom Manage 2012;43(5):902–910;
12. Gayatri D, Efremov L, Kantelhardt EJ, Mikolajczyk R. Quality of life of cancer patients at palliative care units in developing countries: Systematic review of the published literature. Qual Life Res 2021;30(2):315–343;
13. Eldridge SM, Chan CL, Campbell MJ, et al. PAFS consensus group. CONSORT 2010 statement: Extension to randomised pilot and feasibility trials. BMJ 2016;355:i5239;
14. Skivington K, Matthews L, Simpson SA, et al. Framework for the development and evaluation of complex interventions: Gap analysis, workshop and consultation-informed update. Health Technol Assess 2021;25(57):1–132;
15. Zimmermann C, Pope A, Hannon B, et al. Phase II trial of symptom screening with targeted early palliative care for patients with advanced cancer. J Natl Compr Canc Netw 2021;20(4):361–370 e3;
16. Hui D, Puac V, Shelal Z, et al. Effect of dexamethasone on dyspnoea in patients with cancer (ABCD): A parallel-group, double-blind, randomised, controlled trial. Lancet Oncol 2022;23(10):1321–1331;
17. Zlowodzki M, Bhandari M. Outcome measures and implications for sample-size calculations. J Bone Joint Surg Am 2009;91(Suppl 3):35–40;
18. Althubaiti A. Sample size determination: A practical guide for health researchers. J Gen Fam Med 2023;24(2):72–78;
19. Gilron I, Bailey JM, Tu D, et al. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med 2005;352(13):1324–1334;
20. Hui D, Frisbee-Hume S, Wilson A, et al. Effect of lorazepam with haloperidol vs haloperidol alone on agitated delirium in patients with advanced cancer receiving palliative care: A randomized clinical trial. JAMA 2017;318(11):1047–1056;
21. Hardy JR. Placebo-controlled trials in palliative care: The argument for. Palliat Med 1997;11(5):415–418;
22. Shelby-James TM, Hardy J, Agar M, et al. Designing and conducting randomized controlled trials in palliative care: A summary of discussions from the 2010 clinical research forum of the Australian palliative care clinical studies collaborative. Palliat Med 2012;26(8):1042–1047;
23. Hui D, Zhukovsky DS, Bruera E. Which treatment is better? Ascertaining patient preferences with crossover randomized controlled trials. J Pain Symptom Manage 2015;49(3):625–631;
24. Zafar SY, Currow DC, Cherny N, et al. Consensus-based standards for best supportive care in clinical trials in advanced cancer. Lancet Oncol 2012;13(2):e77-82–e82;
25. Bate A. (editor). Evidence-Based Pharmacovigilance: Clinical and Quantitative Aspects. Springer Science+Business Media: New York, NY; 2018.
26. Hoffmann TC, Glasziou PP, Boutron I, et al. Better reporting of interventions: Template for Intervention Description And Replication (TIDieR) checklist and guide. BMJ 2014;348:g1687;
27. Kolva E, Rosenfeld B, Saracino R. Assessing the decision-making capacity of terminally Ill patients with cancer. Am J Geriatr Psychiatry 2018;26(5):523–531;
28. Casarett DJ. Assessing decision-making capacity in the setting of palliative care research. J Pain Symptom Manage 2003;25(4):S6–13;
29. Vijayananthan A, Nawawi O. The importance of good clinical practice guidelines and its role in clinical trials. Biomed Imaging Interv J 2008;4(1):e5;
30. Perez-Gracia JL, Penel N, Calvo E, et al. Streamlining clinical research: An ESMO awareness call to improve sponsoring and monitoring of clinical trials. Ann Oncol 2023;34(1):70–77;
31. National Health and Medical Research Council. Good practice process for site assessment and authorisation phases of clinical trial research governance v2.3. Canberra: National Health and Medical Research Council; 2016. Available from: https://www.nhmrc.gov.au/sites/default/files/documents/good-practice-process.pdf [Last accessed: June 12, 24].

Information & Authors

Information

Published In

cover image Journal of Palliative Medicine
Journal of Palliative Medicine
PubMed: 39167532

History

Published online: 21 August 2024
Accepted: 26 June 2024

Topics

Authors

Affiliations

Taylan Gurgenci
Department of Palliative and Supportive Care, Brisbane, Queensland, Australia.
Cancer Program, Mater Research Institute-University of Queensland, Brisbane, Queensland, Australia.
Cian O’Leary
Cancer Services, Mater Health, Brisbane, Queensland, Australia.
Department of Palliative Care, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Department of Palliative Care, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia.
Department of Palliative Care, Palliative Care Service, St Vincent’s Hospital, Fitzroy, Victoria, Australia.
Eduardo Bruera
Department of Palliative, Rehabilitation, & Integrative Medicine, The University of Texas MD Anderson Cancer, Houston, Texas, USA.
Mellar Davis
Director of Palliative Care Research at Geisinger Medical Center, Geisinger Commonwealth School of Medicine, Scranton PA, Danville, Pennsylvania, USA.
Meera R. Agar
Faculty of Health,IMPACCT, University of Technology Sydney, Sydney, New South Wales, Australia.
David Hui
Department of Palliative, Rehabilitation, & Integrative Medicine, The University of Texas MD Anderson Cancer, Houston, Texas, USA.
Department of Supportive Care, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Sriram Yennu
Department of Palliative, Rehabilitation, & Integrative Medicine, The University of Texas MD Anderson Cancer, Houston, Texas, USA.
Janet Hardy
Cancer Program, Mater Research Institute-University of Queensland, Brisbane, Queensland, Australia.
Pain Relief and Supportive-Palliative Care Unit, La Maddalena Cancer Center, Palermo, Italy.
Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Department of Palliative and Supportive Care, Brisbane, Queensland, Australia.
Department of Palliative Care, St Vincent’s Private Hospital, Brisbane, Queensland, Australia.

Notes

Address correspondence to: Phillip Good, MBBS, PhD, Department of Palliative and Supportive Care, Mater Health, Raymond Terrace, South Brisbane 4101, Queensland, Australia [email protected]

Author Disclosure Statement

D.H. is supported in part by grants from the National Cancer Institute (R01CA214960, R01CA225701, R01CA231471). W.E.R. is partially supported by the NIH/NCI Comprehensive Cancer Center award number P30CA008748. S.Y. – Grant to institution: Pfizer (cachexia study). T.G., J.H., and P.G. – supported in part by Mater Foundation.

Funding Information

D.H. is supported in part by grants from the National Cancer Institute (R01CA214960, R01CA225701, R01CA231471). W.E.R. is partially supported by the NIH/NCI Comprehensive Cancer Center award number P30CA008748.

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