Personalized therapeutic trials, otherwise known as N-of-1 trials, are clinical trials conducted on a single patient, using a multiple-crossover approach to compare different treatments.1 Within personalized trials, patients receive the experimental and control intervention in an alternating, repeated procedure until conclusions can be drawn about the most effective treatment option for the individual. Personalized trials were first introduced into medical practice over 30 years ago, but are now emerging as a novel approach to facilitate personalized medicine and shared decision-making in the face of a growing emphasis on patient-centered care in healthcare.2-5 Typically, population-based studies generate data about the average effect of a medication, whereas personalized trials permit analysis at the individual level and can therefore promote individualized decision-making.3,6,7 Moreover, the format of these trials can help facilitate communication with the patient about the efficacy and side effect profile of medications.
Personalized therapeutic trials have been used to identify optimal medication regimens in multiple clinical settings. For example, they have been conducted to identify the optimal antihypertensive regimens4 and pain regimens8 for individual patients. This was achieved by collecting individual-level data on both efficacy and safety; then leveraging that individual-level data toward personalized decision-making about the optimal regimen. One of the first studies4 demonstrating feasibility of personalized trials focused on antihypertensive regimens in seven patients. All study participants were compliant with at-home blood pressure monitoring and collecting measures of side effect severity. Antihypertensive medication preferences were assessed after reviewing blood pressure and side effects with their provider. All participants recommended personalized trials of antihypertensives to others.
Traditionally, medical decisions are often made based on hypothetical calculations of risk and potential benefit. Personalized trials facilitate decision-making based on actual data which enables precise and individual-level risk-benefit calculations. Prior studies of personalized trials have demonstrated objective increases in patient involvement in decision-making as well as patient decision confidence. A randomized clinical trial8 in pain management care compared outcomes for intervention participants receiving individualized trials to evaluate two pain management regimens versus participants in the control group receiving usual care. At the 6-month follow-up, intervention patients reported higher medication-related shared decision-making scores by 11.9 points (mean scale score 79.6 vs 67.6, 95% confidence interval [2.6 – 21.2], p=0.01). Participants in the personalized therapeutic trial engaged in more medication-related shared decision-making and had more discussions about medication management with their clinicians compared to those who received usual care. Interest in personalized trials is growing in clinical research and has a variety of applications toward patient-centered care.
References
- Guyatt G, Sackett D, Taylor DW, Chong J, Roberts R, Pugsley S. Determining optimal therapy--randomized trials in individual patients. N Engl J Med. 1986;314(14):889-892.
- Kravitz RL, Paterniti DA, Hay MC, Subramanian S, Dean DE, Weisner T, Vohra S, Duan N. Marketing therapeutic precision: Potential facilitators and barriers to adoption of n-of-1 trials. Contemp Clin Trials. 2009;30(5):436-445.
- Duan N, Kravitz RL, Schmid CH. Single-patient (n-of-1) trials: a pragmatic clinical decision methodology for patient-centered comparative effectiveness research. J Clin Epidemiol. 2013;66(8 Suppl):S21-28.
- Kravitz RL. N-of-1 Trials in hypertension are feasible, but are they worthwhile. J Gen Intern Med. 2019;34(6):781-782.
- Kravitz RL, Duan N, eds, and the DEcIDE Methods Center N-of-1 Guidance Panel (Duan N, Eslick I, Gabler NB, Kaplan HC, Kravitz RL, Larson EB, Pace WD, Schmid CH, Sim I, Vohra S). Design and Implementation of N-of-1 Trials: A User’s Guide. AHRQ Publication No. 13(14)-EHC122-EF. Rockville, MD: Agency for Healthcare Research and Quality; February 2014.
- Lillie EO, Patay B, Diamant J, Issell B, Topol EJ, Schork NJ. The n-of-1 clinical trial: the ultimate strategy for individualizing medicine? Per Med. 2011;8(2):161-173.
- Margolis A, Giuliano C. Making the switch: From case studies to N-of-1 trials. Epilepsy Behav Rep. 2019;12:100336. Published 2019 Oct 25. doi:10.1016/j.ebr.2019.100336
- Kravitz RL, Schmid CH, Marois M, Wilsey B, Ward D, Hays RD, Duan N, Wang Y, MacDonald S, Jerant A, Servadio JL, Haddad D, Sim I. Effect of mobile device-supported single-patient multi-crossover trials on treatment of chronic musculoskeletal pain: a randomized clinical trial. JAMA Intern Med. 2018;178(10):1368–1377.doi:10.1001/jamainternmed.2018.3981
