Elise Berliner

GRADE guidelines: 9. Rating up the quality of evidence.

The most common reason for rating up the quality of evidence is a large effect. GRADE suggests considering rating up quality of evidence one level when methodologically rigorous observational studies show at least a two-fold reduction or increase in risk, and rating up two levels for at least a five-fold reduction or increase in risk. Systematic review authors and guideline developers may also consider rating up quality of evidence when a dose-response gradient is present, and when all plausible confounders or biases would decrease an apparent treatment effect, or would create a spurious effect when results suggest no effect. Other considerations include the rapidity of the response, the underlying trajectory of the condition, and indirect evidence.

GRADE guidelines: 11. Making an overall rating of confidence in effect estimates for a single outcome and for all outcomes

GRADE requires guideline developers to make an overall rating of confidence in estimates of effect (quality of evidence-high, moderate, low, or very low) for each important or critical outcome. GRADE suggests, for each outcome, the initial separate consideration of five domains of reasons for rating down the confidence in effect estimates, thereby allowing systematic review authors and guideline developers to arrive at an outcome-specific rating of confidence. Although this rating system represents discrete steps on an ordinal scale, it is helpful to view confidence in estimates as a continuum, and the final rating of confidence may differ from that suggested by separate consideration of each domain. An overall rating of confidence in estimates of effect is only relevant in settings when recommendations are being made. In general, it is based on the critical outcome that provides the lowest confidence.

Planning the Safety of Atrial Fibrillation Ablation Registry Initiative (SAFARI) as a Collaborative Pan-Stakeholder Critical Path Registry Model: A Cardiac Safety Research Consortium “Incubator” Think Tank

Atrial fibrillation (AF) is a major public health problem in the United States that is associated with increased mortality and morbidity. Of the therapeutic modalities available to treat AF, the use of percutaneous catheter ablation of AF is expanding rapidly. Randomized clinical trials examining the efficacy and safety of AF ablation are currently underway; however, such trials can only partially determine the safety and durability of the effect of the procedure in routine clinical practice, in more complex patients, and over a broader range of techniques and operator experience. These limitations of randomized trials of AF ablation, particularly with regard to safety issues, could be addressed using a synergistically structured national registry, which is the intention of the SAFARI. To facilitate discussions about objectives, challenges, and steps for such a registry, the Cardiac Safety Research Consortium and the Duke Clinical Research Institute, Durham, NC, in collaboration with the US Food and Drug Administration, the American College of Cardiology, and the Heart Rhythm Society, organized a Think Tank meeting of experts in the field. Other participants included the National Heart, Lung and Blood Institute, the Centers for Medicare and Medicaid Services, the Agency for Healthcare Research and Quality, the Society of Thoracic Surgeons, the AdvaMed AF working group, and additional industry representatives. The meeting took place on April 27 to 28, 2009, at the US Food and Drug Administration headquarters in Silver Spring, MD. This article summarizes the issues and directions presented and discussed at the meeting.

A Proposed Approach May Help Systematic Reviews Retain Needed Expertise While Minimizing Bias from Nonfinancial Conflicts of Interest

OBJECTIVES Groups such as the Institute of Medicine emphasize the importance of attention to financial conflicts of interest. Little guidance exists, however, on managing the risk of bias for systematic reviews from nonfinancial conflicts of interest. We sought to create practical guidance on ensuring adequate clinical or content expertise while maintaining independence of judgment on systematic review teams. STUDY DESIGN AND SETTING Workgroup members built on existing guidance from international and domestic institutions on managing conflicts of interest. We then developed practical guidance in the form of an instrument for each potential source of conflict. RESULTS We modified the Institute of Medicines definition of conflict of interest to arrive at a definition specific to nonfinancial conflicts. We propose questions for funders and systematic review principal investigators to evaluate the risk of nonfinancial conflicts of interest. Once risks have been identified, options for managing conflicts include disclosure followed by no change in the systematic review team or activities, inclusion on the team along with other members with differing viewpoints to ensure diverse perspectives, exclusion from certain activities, and exclusion from the project entirely. CONCLUSION The feasibility and utility of this approach to ensuring needed expertise on systematic reviews and minimizing bias from nonfinancial conflicts of interest must be investigated.

Inpatient Costs of Major Cardiovascular Events

ObjectiveMany trials of new therapies for cardiovascular disease include economic measures to assess the impact of treatment on healthcare costs, however, it is difficult to compare results between trials due to variation in methods for assigning costs. Therefore we developed a standard library of inpatient hospital costs for major cardiovascular events commonly reported in trials for new cardiovascular therapies.DesignMean and median hospital charges for each event were calculated from Medicare admissions selected by ICD-9-CM codes from the most recent Healthcare Cost and Utilisation Project (HCUP) Nationwide Inpatient Sample (NIS) database available. Charges were converted to costs using the cost-to-charge ratio from the most recent Medicare cost report data and updated to 1999 using a model derived from the Medicare Payment Advisory Commission (MedPAC) forecast to recommend annual updates to Medicare.ResultsTotal hospital costs for medical events ranged from

Fit for purpose: perspectives on rapid reviews from end-user interviews

US3654 (1999 values) to

mobilityRERC State of the Science Conference: considerations for developing an evidence base for wheeled mobility and seating service delivery

US7833; total hospital costs for surgery and procedures ranged from

Adopting medical technology.

US7054 to

Does information from ClinicalTrials.gov increase transparency and reduce bias? Results from a five-report case series

US46 317. The distribution of hospital costs is skewed with median costs and lengths of stay lower than mean values. Costs for patients who died in the hospital were generally higher than costs for patients who were discharged.ConclusionsThe library of costs was calculated using a uniform method based on publicly available and easily accessible data and may be updated from year to year. This method provides standardised estimates of hospital costs that can be used in economic analyses of cardiovascular clinical trials.

Hyperbaric oxygen for treating wounds: a systematic review of the literature.

BackgroundThere is increasing demand for rapid reviews and timely evidence synthesis. The goal of this project was to understand end-user perspectives on the utility and limitations of rapid products including evidence inventories, rapid responses, and rapid reviews.MethodsInterviews were conducted with key informants representing: guideline developers (n = 3), health care providers/health system organizations (n = 3), research funders (n = 1), and payers/health insurers (n = 1). We elicited perspectives on important characteristics of systematic reviews, acceptable methods to streamline reviews, and uses of rapid products. We analyzed content of the interview transcripts and identified themes and subthemes.ResultsKey informants identified the following as critical features of evidence reviews: (1) originating from a reliable source (i.e., conducted by experienced reviewers from an established research organization), (2) addressing clinically relevant questions, and (3) trusted relationship between the user and producer. Key informants expressed strong preference for the following review methods and characteristics: use of evidence tables, quality rating of studies, assessments of total evidence quality/strength, and use of summary tables for results and conclusions. Most acceptable trade-offs to increase efficiencies were limiting the literature search (e.g., limiting search dates or language) and performing single screening of citations and full texts for relevance. Key informants perceived rapid products (particularly evidence inventories and rapid responses) as useful interim products to inform downstream investigation (e.g., whether to proceed with a full review or guideline, direction for future research). Most key informants indicated that evidence analysis/synthesis and quality/strength of evidence assessments were important for decision-making. They reported that rapid reviews in particular were useful for guideline development on narrow topics, policy decisions when a quick turn-around is needed, decision-making for practicing clinicians in nuanced clinical settings, and decisions about coverage by payers/health insurers. Rapid reviews may be more relevant within specific clinical settings or health systems; whereas, broad/national guidelines often need a traditional systematic review.ConclusionsKey informants interviewed in our study indicated that evidence inventories, rapid responses, and rapid reviews have utility in specific decisions and contexts. They indicated that the credibility of the review producer, relevance of key questions, and close working relationship between the end-user and producer are critical for any rapid product. Our findings are limited by the sample size which may have been too small to reach saturation for the themes described.