Objective To determine the real world effectiveness of statins and impact of baseline factors on low-density lipoprotein cholesterol (LDL-C) reduction among children and adolescents. Study design We analyzed data prospectively collected from a quality improvement initiative in the Boston Children’s Hospital Preventive Cardiology Program. We included patients ≤ 21 years of age initiated on statins between September 2010 and March 2014. The primary outcome was first achieving goal LDL-C, defined as <130 mg/dL, or <100 mg/dL with high-level risk factors (e.g. diabetes, etc.). Cox proportional hazards models assessed the impact of baseline clinical and lifestyle factors. Results Among the 1521 pediatric patients evaluated in 3813 clinical encounters over 3.5 years, 97 patients (6.3%) were started on statin therapy and had follow-up data (median age 14 [IQR 7] years), 54% were female, 24% obese, 62% with at least one lifestyle risk factor. The median baseline LDL-C was 215 (IQR 78) mg/dL and median follow-up after starting statin was 1.0 (IQR 1.3) year. The cumulative probability of achieving LDL-C goal within 1 year was 60% (95% CI 47, 69). Male sex (HR 0.5 [95% CI 0.3, 0.8]) and higher baseline LDL-C (HR 0.92 [95% CI 0.87, 0.98] per 10 mg/dL) were associated with not achieving LDL-C goals, but not age, BMI percentile, lifestyle factors or family history. Conclusions The majority of pediatric patients started on statins reached LDL-C treatment goals within 1 year. Males and those with higher baseline LDL-C were less likely to be successful and may require increased support.

A personalized treatment strategy formalizes evidence-based treatment selection by mapping patient information to a recommended treatment. Personalized treatment strategies can produce better patient outcomes while reducing cost and treatment burden. Thus, among clinical and intervention scientists, there is a growing interest in conducting randomized clinical trials when one of the primary aims is estimation of a personalized treatment strategy. However, at present, there are no appropriate sample size formulae to assist in the design of such a trial. Furthermore, because the sampling distribution of the estimated outcome under an estimated optimal treatment strategy can be highly sensitive to small perturbations in the underlying generative model, sample size calculations based on standard (uncorrected) asymptotic approximations or computer simulations may not be reliable. We offer a simple and robust method for powering a single stage, two-armed randomized clinical trial when the primary aim is estimating the optimal single stage personalized treatment strategy. The proposed method is based on inverting a plugin projection confidence interval and is thereby regular and robust to small perturbations of the underlying generative model. The proposed method requires elicitation of two clinically-meaningful parameters from clinical scientists and uses data from a small pilot study to estimate nuisance parameters which are not easily elicited. The method performs well in simulated experiments and is illustrated using data from a pilot study of time to conception and fertility awareness.

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Introduction: Targeting LDL-C goals for statin therapy is currently recommended for children and adolescents in NHLBI pediatric guidelines; however, there is limited information about clinical factors, especially modifiable ones, that impact successful achievement of LDL-C goals. Methods: We analyzed data prospectively collected as part of a quality improvement initiative, SCAMP® (Standardized Clinical Assessment and Management Program), in the Preventive Cardiology Clinic at Boston Children’s Hospital, Boston, MA. We included patients initiated on statin therapy from September 2010 to March 2014. Achieving LDL target was defined as an LDL-C < 130 mg/dL or an LDL-C < 100mg/dL with a high level risk factor (i.e. diabetes, etc.). The impact of baseline CVD risk factors were assessed in Cox proportional hazards models. Results: Among the 1521 pediatric patients and 3813 clinical encounters that occurred over the 3.5 year period, 116 patients were defined as initiating statin therapy. Complete data was available on 79 patients (mean [SD] age 14 [4] years; 47% female; median [IQR] LDL-C 215 [79] mg/dL). The probability of achieving LDL-C goal within 365 and 500 days of starting a statin was 0.55 (95% CI 0.44-0.68) and 0.67 (0.55-0.79), respectively; Figure 1. In univariate analyses, female sex (p=0.01) and lower baseline LDL-C (p=0.04) was associated with more rapid achievement of LDL-C goals, but not age (p=0.8), BMI (p=0.2), exercise (p=0.6), nutritional factors (p=0.3), screen time (p=0.3), cigarette smoking (p=0.9), or family history of early CVD (p=0.3). Conclusions: The majority of children reached LDL-C treatment goals with statin therapy. Baseline modifiable lifestyle CVD risk factors such as diet and exercise were not associated with achieving LDL-C goal on statin therapy in children and adolescents. Increased support and monitoring may be needed, particularly for males, in order to achieve therapy goals.