The objective of the parent grant (R01LM012836) is to develop, test, and implement an innovative technology platform for conducting N-of-1 trials that transforms precision therapeutics. Right now, clinicians are engaging in clinical encounters at which they are trying to determine the best therapy for individual patients. These encounters are likely to be unsuccessful. Clinicians rely on the best available evidence (e.g., results from phase III randomized clinical trials; RCTs) for recommending therapies to a patient. Yet, conventional, between-patient RCTs only provide estimates of the effect of therapies on the average patient in those trials. Individual patients, however, often respond differently than the average patient in the phase III RCTs, and thus, heterogeneity of therapy response plagues these clinical decisions every day. The most scientifically rigorous-- and potentially transformative--method for determining optimal therapy for a patient is a single-patient (N-of-1) trial. N-of-1 trials are multiple crossover trials, usually randomized, and often masked, conducted within a single patient, with data collected objectively, continuously, and in the real-world, for a sufficient time period to determine whether the therapy, compared to a placebo or other active therapy, is optimal for a particular patient. They also yield information on off-target actions, such as side-effects, so that a more complex picture can emerge about the overall benefits and harms of a therapy for an individual patient. Clinicians and patients do not routinely engage in this type of scientific endeavor because they lack the tools. The goal of this Research Administrative Supplement to Promote Diversity in Health-Related Research is to enhance and support the independent research career of Dr. Lyndonna Marrast, an internist dedicated to addressing health disparities found among racial and ethnic minorities. To support the research career development of the candidate and to stay within the scope of the parent grant, Dr. Marrast will enhance the alpha testing phase of our grant by conducting qualitative interviews with physicians and patients from racial and ethnic minorities about the acceptability and usefulness of our Personalized Trial platform. This meets with her training aim, to receive training in the conduct of formative and qualitative research, and aids the parent grant by enriching the qualitative information available from patients and physicians from under-represented backgrounds. As stated in our original grant, ?A subset of patients and providers who complete these alpha test N-of-1 trials (N=12) will also be interviewed after participating in an N-of-1 trial to provide essential pilot usability data for the next phase of testing. From this alpha-testing of our platform across health conditions, we expect to collect sufficient data from clinicians and patients about burdens and flaws to design our final prototype.? We now intend to add 12 physician interviews and 24 patient interviews to enhance the alpha-testing phase of our parent grant.
We need to re-imagine the clinical encounter at which therapies are selected, into one that is capable of identifying therapies with maximal benefit and minimal harm for individual patients. Such a precision therapeutics clinical encounter requires de novo creation and extensive testing of an automated electronic platform that would allow clinicians (or patients, or scientists) to collect objective, real-world outcome data on the usefulness of a therapy for an individual patient. In the spirit of groundbreaking, paradigm-shifting research, we propose to re-engineer clinical practice, to make N-of-1 trials accessible and feasible so that precision therapeutics can become widely available.
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| Cheung, Ying Kuen; Hsueh, Pei-Yun Sabrina; Qian, Min et al. (2017) Are Nomothetic or Ideographic Approaches Superior in Predicting Daily Exercise Behaviors? Methods Inf Med 56:452-460 |
| Kronish, Ian M; Alcántara, Carmela; Duer-Hefele, Joan et al. (2017) Patients and primary care providers identify opportunities for personalized (N-of-1) trials in the mobile health era. J Clin Epidemiol 89:236-237 |
