Extending the vision of adaptive point-of-care platform trials to improve targeted use of drug therapy regimens: An agile approach in the learning healthcare system toolkit.

Objectives: Improving the targeted use of drug regimens requires robust real-world evidence (RWE) to address the uncertainties that remain regarding their real-world performance following market entry. However, challenges in the current state of RWE production limit its impact on clinical decisions, as well as its operational scalability and sustainability. We propose an adaptive point-of-care (APoC) platform trial as an approach to RWE production that improves both clinical and operational efficiencies.

Examining Endpoint Concordance in Clinical Trials and Real-World Clinical Practice to Advance Real-World Evidence Utilization.

Real-world evidence (RWE) is increasingly contributing to more informed decisions regarding the optimal access to and use of therapeutics to improve patient outcomes. However, in many cases, a disconnect between evidence derived from clinical trials and the RWE that follows market approval impedes the potential value and widespread adoption of RWE to optimize patient care. Collaborators with the Learning Ecosystems Accelerator for Patient-centered, Sustainable innovation (LEAPS), a major project of the Tufts Medical Center [formally Massachusetts Institute of Technology (MIT)] NEW Drug Development ParadIGmS (NEWDIGS) initiative, propose assessing the relationship between efficacy endpoints used in randomized controlled trials (RCTs) and effectiveness measures that inform treatment decisions within real-world clinical settings as one way to bridge this divide and further leverage RWE to improve care and patient outcomes.

Precision Reimbursement for Precision Medicine: Using Real-World Evidence to Evolve From Trial-and-Project to Track-and-Pay to Learn-and-Predict.

Basic scientists and drug developers are accelerating innovations toward the goal of precision medicine. Regulators create pathways for timely patient access to precision medicines, including individualized therapies. Healthcare payors acknowledge the need for change but downstream innovation for coverage and reimbursement is only haltingly occurring.

A Useful and Sustainable Role for N-of-1 Trials in the Healthcare Ecosystem.

Clinicians and patients often try a treatment for an initial period to inform longer-term therapeutic decisions. A more rigorous approach involves N-of-1 trials. In these single-patient crossover trials, typically conducted in patients with chronic conditions, individual patients are given candidate treatments in a double-blinded, random sequence of alternating periods to determine the most effective treatment for that patient.

Dynamic Dossier in the Cloud: A Sociotechnical Architecture for a Real-Time and Metrics-Based Data Tracking System with Gene and Cell Therapies as a Case Study.

Background: Data sharing among stakeholders in the development, access, and use of drug therapies is critical but the current system and process are inefficient.

Methods: We take a Systems Engineering approach with a realistic use case to propose a scalable design for multi-stakeholder data sharing.

Results: We make three major contributions to the drug development and healthcare communities: first, a methodology for developing a multi-stakeholder data sharing system, with its focus on high-level requirements that influence the design of the system architecture and technology choice; second, the development of a realistic use case for long-term patient and therapy data tracking and sharing in the use of potentially curative and durable gene and cell therapies.

A Pragmatic Clinical Trial to Compare the Real-World Effectiveness of V-Go versus Standard Delivery of Insulin in Patients with Advanced Type 2 Diabetes.

Background: Many patients with type 2 diabetes mellitus (T2DM) do not have adequate glycemic control, leading to poor patient outcomes and high healthcare costs.

Objective: This prospective pragmatic clinical trial evaluated V-Go, a wearable insulin delivery device, compared with standard treatment optimization (STO) among insulin-treated patients with T2DM in a real-world, community-based practice setting.

Methods: Study sites, rather than individual patients, were randomized to V-Go or STO via cluster randomization.

Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 2.

Evidence-based health care decision making requires comparison of all relevant competing interventions. In the absence of randomized controlled trials involving a direct comparison of all treatments of interest, indirect treatment comparisons and network meta-analysis provide useful evidence for judiciously selecting the best treatment(s). Mixed treatment comparisons, a special case of network meta-analysis, combine direct evidence and indirect evidence for particular pairwise comparisons, thereby synthesizing a greater share of the available evidence than traditional meta-analysis.

Outcomes of erythropoiesis-stimulating agents in cancer patients with chemotherapy-induced anemia.

Purpose: To assess the clinical and economic outcomes among patients with chemotherapy-induced anemia (CIA) treated with United States Food and Drug Administration-approved fixed dosing regimens of erythropoiesis-stimulating agents (ESA).

Methods: Data were employed from the Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) registry to evaluate CIA patients who were initiated on either epoetin alfa (EPO) 40,000 Units (U) or darbepoetin alfa (DARB) 500 micrograms (mcg) between January 1, 2006 and May 8, 2009. Study measurements included ESA treatment dose and dose ratio, changes in hemoglobin (Hb) levels from baseline, and cumulative ESA costs.

Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) : a registry for characterizing anaemia management and outcomes in oncology patients.

Background And Objective: To report the design, methodology, implementation and initial results of the Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) Registry, the first US patient registry to collect and report on practice patterns and outcomes associated with erythropoiesis-stimulating therapy (EST) for anaemia management in oncology patients.

Methods: DOSE is a prospective ongoing registry of oncology patients treated with epoetin-alpha or darbepoetin-alpha. Patients from either community or academic centres who meet prespecified entry criteria are eligible for inclusion in the registry.

Effect of recombinant human erythropoietin combined with granulocyte/ macrophage colony-stimulating factor in the treatment of patients with myelodysplastic syndrome. GM/EPO MDS Study Group.

This randomized, placebo-controlled trial was designed to assess the efficacy and safety of therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (epoetin alfa) in anemic, neutropenic patients with myelodysplastic syndrome. Sixty-six patients were enrolled according to the following French-American-British classification: refractory anemia (20), refractory anemia with excess blasts (35), refractory anemia with ringed sideroblasts (9), and refractory anemia with excess blasts in transformation (2). Patients were stratified by their serum erythropoietin levels (less than or equal to 500 mU/mL, n = 37; greater than 500 mU/mL, n = 29) and randomized, in a 2:1 ratio, to either GM-CSF (0.

The predictive power of baseline hemoglobin for transfusion risk in surgery patients.

Preoperative hemoglobin concentration may be an important predictor of transfusion risk in surgical procedures with significant expected blood loss. Contemporary studies investigating transfusion risk with regard to the relationship between perioperative administration of Epoetin alfa and baseline hemoglobin provide data to test this hypothesis. The predictive power of seven preoperative variables (hemoglobin concentration, age, erythropoietin level, ferritin concentration, serum iron, total iron-binding capacity, and predicted blood volume) on transfusion risk was examined via retrospective logistic regression analysis of 276 orthopedic surgical patients.

Recombinant Human Erythropoietin (rHuEPO) for the Treatment of the Anemia of Cancer.

Advanced cancer is frequently associated with a significant anemia that may be due to the disease itself or the effect of concomitantly administered chemotherapeutic agents. In a series of double-blind, placebo-controlled trials, three populations of anemic cancer patients were randomized to rHuEPO or placebo. The three populations were: A) patients not receiving concomitant chemotherapy, B) patients receiving chemotherapeutic regimens which did not contain cisplatin, and C) patients receiving chemotherapeutic regimens which contained cisplatin.

Recombinant human erythropoietin therapy for anemic cancer patients receiving cisplatin chemotherapy.

Purpose: To assess whether the administration of recombinant human erythropoietin (r-HuEPO) would increase the hematocrit, reduce the requirement for transfusion, and improve the quality of life in anemic cancer patients receiving myelosuppressive, cisplatin-based chemotherapy.

Patients And Methods: One hundred thirty-two anemic cancer patients receiving cyclic, cisplatin-containing, myelosuppressive chemotherapy were evaluated. Patients received either r-HuEPO (150 U/kg) or placebo, subcutaneously, three times a week for 3 months.

Effects of heteroscedasticity upon certain analyses when regression lines are not parallel.

The two sample analysis of covariance model is considered where the regression lines are found not to be parallel. There are two analyses often utilized in this case. One is to obtain a standard confidence interval for the covariate value where the two lines intersect, and the other is to find a simultaneous confidence region for the difference between the regression lines.

The impact of prenatal care on the outcome of pregnancy.

In a 12-months' prospective project all women delivering at the Soroka Medical Center, Beer-Sheba, Israel, were studied with regard to the type of prenatal care (P.C.) and the outcome of pregnancy.

Prognostic factors in polymyositis/dermatomyositis. A computer-assisted analysis of ninety-two cases.

An effort was made to identify all patients with polymyositis/dermatomyositis (PM/DM) admitted to hospitals in Israel from 1956-1976. The diagnosis of PM/DM was retrospectively reviewed in 92 (46 definite, 26 probable, and 20 possible) cases. The most common complaints and physical findings in the course of the disease were muscle weakness (86 patients), rash (53 patients), arthritis or arthralgia (39 patients), and dysphagia (35 patients).