Stacey Uhl

Autologous hematopoietic cell transplantation for multiple sclerosis: a systematic review

Background and objectives: The purpose of this systematic review was to evaluate the safety and efficacy of autologous hematopoietic cell transplantation in patients with progressive multiple sclerosis (MS) refractory to conventional medical treatment. Methods: Eight case series met our a priori inclusion criteria for the primary outcome of progression-free survival. Individual study quality was rated using an 11-item scale for case series. The strength of the overall body of evidence for each outcome was rated using a system developed by the ECRI Institute. Data from different studies were statistically combined using meta-analysis. An additional six studies were included for a summary of mortality and morbidity. Results: For secondary progressive MS, immunoablative therapy with autologous bone marrow/peripheral blood stem cell transplantation was associated with higher progression-free survival (up to 3 years following treatment) when using intermediate-intensity conditioning regimens compared with high-intensity conditioning regimens. The evidence was insufficient to determine whether the treatment was effective in patients with other types of MS. Treatment-related mortality was about 2.7%. Conclusions: Patients with secondary progressive MS refractory to conventional medical treatment have longer progression-free survival following autologous stem cell transplantation with intermediate-intensity conditioning regimens than with high-intensity conditioning regimens.

Calcineurin Inhibitor Minimization, Conversion, Withdrawal, and Avoidance Strategies in Renal Transplantation: A Systematic Review and Meta-Analysis.

Despite their clinical efficacy, concerns about calcineurin inhibitor (CNI) toxicity make alternative regimens that reduce CNI exposure attractive for renal transplant recipients. In this systematic review and meta‐analysis, we assessed four CNI immunosuppression strategies (minimization, conversion, withdrawal, and avoidance) designed to reduce CNI exposure and assessed the impact of each on patient and allograft survival, acute rejection and renal function. We evaluated 92 comparisons from 88 randomized controlled trials and found moderate‐ to high‐strength evidence suggesting that minimization strategies result in better clinical outcomes compared with standard‐dose regimens; moderate‐strength evidence indicating that conversion to a mammalian target of rapamycin inhibitor or belatacept was associated with improved renal function but increased rejection risk; and moderate‐ to high‐strength evidence suggesting planned CNI withdrawal could result in improved renal function despite an association with increased rejection risk. The evidence base for avoidance studies was insufficient to draw meaningful conclusions. The applicability of the review is limited by the large number of studies examining cyclosporine‐based strategies and low‐risk populations. Additional research is needed with tacrolimus‐based regimens and higher risk populations. Moreover, research is necessary to clarify the effect of induction and adjunctive agents in alternative immunosuppression strategies and should include more comprehensive and consistent reporting of patient‐centered outcomes.

Assessing equivalence and noninferiority

OBJECTIVE For systematic reviews, no guidance exists for what review methods support valid conclusions of equivalence (EQ) and noninferiority (NI). To provide such guidance, we convened a workgroup of 13 experienced systematic reviewers from seven evidence-based practice centers (EPCs) and the Agency for Healthcare Research and Quality (AHRQ). STUDY DESIGN AND SETTING The Lead EPC first performed two methods projects intended to assist the workgroup in clarifying the context, prioritizing the issues, targeting the scope, and summarizing the state of the art. RESULTS Based on expert opinion, we devised guidance in four areas: 1) Unique risk of bias issues for trials self-identifying as EQ-NI trials; 2) Setting the reviewers minimum important difference; 3) Analytic foundations for concluding EQ or NI; and 4) Language considerations when concluding EQ or NI. CONCLUSION This article summarizes the main recommendations, and the full guidance chapter appears on the AHRQ Web site.

AHRQ series on complex intervention systematic reviews-paper 2: Defining complexity, formulating scope, and questions

BACKGROUND The early stages of a systematic review set the scope and expectations. This can be particularly challenging for complex interventions given their multidimensional and dynamic nature. RATIONALE This paper builds on concepts introduced in paper 1 of this series. It describes the methodological, practical, and philosophical challenges and potential approaches for formulating the questions and scope of systematic reviews of complex interventions. Furthermore, it discusses the use of theory to help organize reviews of complex interventions. DISCUSSION Many interventions in medicine, public health, education, social services, behavioral health, and community programs are complex, and they may not fit neatly within the established paradigm for reviews of straightforward interventions. This paper provides conceptual and operational guidance for these early stages of scope formulation to assist authors of systematic reviews of complex interventions.

Defining the benefits and challenges of stakeholder engagement in systematic reviews

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Comparative Effectiveness Research 2015:5 13–19 Comparative Effectiveness Research Dovepress

Systematic Review of Calcineurin Inhibitor Monitoring and Dosing Strategies in Renal Transplantation: Notice of a New Report Funded by the Agency for Healthcare Research and Quality

The calcineurin inhibitors (CNIs)6 tacrolimus (TAC) and cyclosporine A (CsA) are effective immunosuppressive agents for renal transplantation but require careful management to avoid toxicity. Routine therapeutic monitoring guides dosing, but uncertainty surrounds different monitoring methods and time points. Additionally, the effectiveness of strategies to reduce CNI exposure is unclear. A recent report commissioned by the Agency for Healthcare Research and Quality (AHRQ) based on research conducted by the ECRI Institute–Penn Medicine Evidence-based Practice Center to address these questions is now available (https://www.effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports). The systematic review evaluates the evidence for 3 questions. The first question compared immunoassay analysis with liquid chromatographic or mass spectrometric analytical techniques for therapeutic monitoring of CNIs. The second question examined CsA monitoring time points, and the third question evaluated alternatives to full-dose CNI regimens. The review included 105 studies. Eleven studies addressing the analytic validity of monitoring …