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Personalized treatment selection using data from crossover designs with carry-over effects.

ABSTRACT: In this work, we propose a semiparametric method for estimating the optimal treatment for a given patient based on individual covariate information for that patient when data from a crossover design are available. Here, we assume there are carry-over effects for patients switching from one treatment to another. For the K treatment (K???2) scenario, we show that nonparametric estimation of carry-over effects can have the undesirable property that comparison of treatment means can only be done using independent outcome measurements from different groups of patients rather than using available joint measurements for each patient. To overcome this barrier, we compare probabilities of outcome variable of each treatment dominating outcome variables for all other treatments conditional on patient-specific scores constructed from patient covariates. We suggest single-index models as appropriate models connecting outcome variables to covariates and our empirical investigations show that frequencies of correct treatment assignments are highly accurate. The proposed method is also rather robust against departures from a single-index model structure. We also conduct a real data analysis to show the applicability of the proposed procedure.

SUBMITTER: Siriwardhana C

PROVIDER: S-EPMC6842056 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Personalized treatment selection using data from crossover designs with carry-over effects.

Siriwardhana Chathura C Kulasekera K B KB Datta Somnath S

Statistics in medicine 20191021 28

In this work, we propose a semiparametric method for estimating the optimal treatment for a given patient based on individual covariate information for that patient when data from a crossover design are available. Here, we assume there are carry-over effects for patients switching from one treatment to another. For the K treatment (K ≥ 2) scenario, we show that nonparametric estimation of carry-over effects can have the undesirable property that comparison of treatment means can only be done usi ...[more]

PMID: 31637762

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Project description:BackgroundStatins are a class of drugs that lower cholesterol levels in the blood by inhibiting an enzyme called 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. High cholesterol levels can lead to plaque buildup in the arteries, which can cause Atherosclerotic Cardiovascular Disease(ASCVD). Statins can reduce the risk of ASCVD events by about 25-35% but they might be associated with symptoms such as muscle pain, liver damage, or diabetes. As a result, this leads to a strong reason to discontinue statin therapy, which increases the risk of cardiovascular events and mortality and becomes a public-health problem.To solve this problem, in the previous work, we proposed a framework to produce a proactive strategy, called a personalized statin treatment plan (PSTP) to minimize the risks of statin-associated symptoms and therapy discontinuation when prescribing statin. In our previous PSTP framework, three limitations remain, and they can influence PSTP usability: (1) Not taking the counterfactual predictions and confounding bias into account. (2) The balance between multiple drug-prescribing objectives (especially trade-off objectives), such as tradeoff between benefits and risks. (3) Evaluating PSTP in retrospective data.ObjectivesThis manuscript aimed to provide solutions for the three abovementioned problems to improve PSTP robustness to produce a proactive strategy for statin prescription that can maximize the benefits (low-density lipoprotein cholesterol (LDL-C) reduction) and minimize risks (statin-associated symptoms and therapy discontinuation) at the same time.MethodsWe applied overlapping weighting counterfactual survival risk prediction (CP), multiple objective optimization (MOO), and clinical trial simulation (CTS) which consists of Random Arms, Clinical Guideline arms, PSTP Arms, and Practical Arms to improve the PSTP framework and usability.ResultsIn addition to highly balanced covariates, in the CTS, the revised PSTP showed improvements in lowering the SAS risks overall compared to other arms across all time points by at most 7.5% to at least 1.0% (Fig. 8(a)). It also has the better flexibility of identifying the optimal Statin across all time points within one year.ConclusionWe demonstrated feasibility of robust and trustworthy counterfactual survival risk prediction model. In CTS, we also demonstrated the PSTP with Pareto optimization can personalize optimal balance between Statin benefits and risks.

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Personalized treatment selection using data from crossover designs with carry-over effects.

Publications

Personalized treatment selection using data from crossover designs with carry-over effects.

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