Roger Chou

Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force.

BACKGROUNDnScreening can detect prostate cancer at earlier, asymptomatic stages, when treatments might be more effective.nnnPURPOSEnTo update the 2002 and 2008 U.S. Preventive Services Task Force evidence reviews on screening and treatments for prostate cancer.nnnDATA SOURCESnMEDLINE (2002 to July 2011) and the Cochrane Library Database (through second quarter of 2011).nnnSTUDY SELECTIONnRandomized trials of prostate-specific antigen-based screening, randomized trials and cohort studies of prostatectomy or radiation therapy versus watchful waiting, and large observational studies of perioperative harms.nnnDATA EXTRACTIONnInvestigators abstracted and checked study details and quality using predefined criteria.nnnDATA SYNTHESISnOf 5 screening trials, the 2 largest and highest-quality studies reported conflicting results. One found that screening was associated with reduced prostate cancer-specific mortality compared with no screening in a subgroup of men aged 55 to 69 years after 9 years (relative risk, 0.80 [95% CI, 0.65 to 0.98]; absolute risk reduction, 0.07 percentage point). The other found no statistically significant effect after 10 years (relative risk, 1.1 [CI, 0.80 to 1.5]). After 3 or 4 screening rounds, 12% to 13% of screened men had false-positive results. Serious infections or urine retention occurred after 0.5% to 1.0% of prostate biopsies. There were 3 randomized trials and 23 cohort studies of treatments. One good-quality trial found that prostatectomy for localized prostate cancer decreased risk for prostate cancer-specific mortality compared with watchful waiting through 13 years of follow-up (relative risk, 0.62 [CI, 0.44 to 0.87]; absolute risk reduction, 6.1%). Benefits seemed to be limited to men younger than 65 years. Treating approximately 3 men with prostatectomy or 7 men with radiation therapy instead of watchful waiting would each result in 1 additional case of erectile dysfunction. Treating approximately 5 men with prostatectomy would result in 1 additional case of urinary incontinence. Prostatectomy was associated with perioperative death (about 0.5%) and cardiovascular events (0.6% to 3%), and radiation therapy was associated with bowel dysfunction.nnnLIMITATIONSnOnly English-language articles were included. Few studies evaluated newer therapies.nnnCONCLUSIONnProstate-specific antigen-based screening results in small or no reduction in prostate cancer-specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary.nnnPRIMARY FUNDING SOURCEnAgency for Healthcare Research and Quality.

Effectiveness and Harms of Recombinant Human Bone Morphogenetic Protein-2 in Spine Fusion: A Systematic Review and Meta-analysis

BACKGROUNDnRecombinant human bone morphogenetic protein-2 (rhBMP-2) is used as a bone graft substitute in spinal fusion, which unites (fuses) bones in the spine. The accuracy and completeness of journal publications of industry-sponsored trials on the effectiveness and harms of rhBMP-2 has been called into question.nnnPURPOSEnTo independently assess the effectiveness and harms of rhBMP-2 in spinal fusion and reporting bias in industry-sponsored journal publications.nnnDATA SOURCESnIndividual-patient data (IPD) from 17 industry-sponsored studies; related internal documents; and searches of MEDLINE (1996 to August 2012), other databases, and reference lists.nnnSTUDY SELECTIONnRandomized, controlled trials (RCTs) and cohort studies of rhBMP-2 versus any control and uncontrolled studies of harms.nnnDATA EXTRACTIONnEffectiveness outcomes in IPD were recalculated using consistent definitions. Study characteristics and results were abstracted by 1 investigator and confirmed by another. Two investigators independently assessed quality using predefined criteria.nnnDATA SYNTHESISnThirteen RCTs and 31 cohort studies were included. For lumbar spine fusion, rhBMP-2 and iliac crest bone graft were similar in overall success, fusion, and other effectiveness measures and in risk for any adverse event, although rates were high across interventions (77% to 93% at 24 months from surgery). For anterior lumbar interbody fusion, rhBMP-2 was associated with nonsignificantly increased risk for retrograde ejaculation and urogenital problems. For anterior cervical spine fusion, rhBMP-2 was associated with increased risk for wound complications and dysphagia. At 24 months, the cancer risk was increased with rhBMP-2 (risk ratio, 3.45 [95% CI, 1.98 to 6.00]), but event rates were low and cancer was heterogeneous. Early journal publications misrepresented the effectiveness and harms through selective reporting, duplicate publication, and underreporting.nnnLIMITATIONSnOutcome assessment was not blinded, and ascertainment of harms in trials was poor. No trials were truly independent of industry sponsorship.nnnCONCLUSIONnIn spinal fusion, rhBMP-2 has no proven clinical advantage over bone graft and may be associated with important harms, making it difficult to identify clear indications for rhBMP-2. Earlier disclosure of all relevant data would have better informed clinicians and the public than the initial published trial reports did.nnnPRIMARY FUNDING SOURCEnYale University and Medtronic.

Diagnostic Imaging for Low Back Pain: Advice for High-Value Health Care From the American College of Physicians

Diagnostic imaging is indicated for patients with low back pain only if they have severe progressive neurologic deficits or signs or symptoms that suggest a serious or specific underlying condition. In other patients, evidence indicates that routine imaging is not associated with clinically meaningful benefits but can lead to harms. Addressing inefficiencies in diagnostic testing could minimize potential harms to patients and have a large effect on use of resources by reducing both direct and downstream costs. In this area, more testing does not equate to better care. Implementing a selective approach to low back imaging, as suggested by the American College of Physicians and American Pain Society guideline on low back pain, would provide better care to patients, improve outcomes, and reduce costs.

High-Value, Cost-Conscious Health Care: Concepts for Clinicians to Evaluate the Benefits, Harms, and Costs of Medical Interventions

Health care costs in the United States are increasing unsustainably, and further efforts to control costs are inevitable and essential. Efforts to control expenditures should focus on the value, in addition to the costs, of health care interventions. Whether an intervention provides high value depends on assessing whether its health benefits justify its costs. High-cost interventions may provide good value because they are highly beneficial; conversely, low-cost interventions may have little or no value if they provide little benefit. Thus, the challenge becomes determining how to slow the rate of increase in costs while preserving high-value, high-quality care. A first step is to decrease or eliminate care that provides no benefit and may even be harmful. A second step is to provide medical interventions that provide good value: medical benefits that are commensurate with their costs. This article discusses 3 key concepts for understanding how to assess the value of health care interventions. First, assessing the benefits, harms, and costs of an intervention is essential to understand whether it provides good value. Second, assessing the cost of an intervention should include not only the cost of the intervention itself but also any downstream costs that occur because the intervention was performed. Third, the incremental cost-effectiveness ratio estimates the additional cost required to obtain additional health benefits and provides a key measure of the value of a health care intervention.

Long-Term Opioid Therapy Reconsidered

In the past 20 years, primary care physicians have greatly increased prescribing of long-term opioid therapy. However, the rise in opioid prescribing has outpaced the evidence regarding this practice. Increased opioid availability has been accompanied by an epidemic of opioid abuse and overdose. The rate of opioid addiction among patients receiving long-term opioid therapy remains unclear, but research suggests that opioid misuse is not rare. Recent studies report increased risks for serious adverse events, including fractures, cardiovascular events, and bowel obstruction, although further research on medical risks is needed. New data indicate that opioid-related risks may increase with dose. From a societal perspective, higher-dose regimens account for the majority of opioids dispensed, so cautious dosing may reduce both diversion potential and patient risks for adverse effects. Limiting long-term opioid therapy to patients for whom it provides decisive benefits could also reduce risks. Given the warning signs and knowledge gaps, greater caution and selectivity are needed in prescribing long-term opioid therapy. Until stronger evidence becomes available, clinicians should err on the side of caution when considering this treatment.

Blood Tests to Diagnose Fibrosis or Cirrhosis in Patients With Chronic Hepatitis C Virus Infection: A Systematic Review

BACKGROUNDnMany blood tests have been proposed as alternatives to liver biopsy for identifying fibrosis or cirrhosis.nnnPURPOSEnTo evaluate the diagnostic accuracy of blood tests to identify fibrosis or cirrhosis in patients with hepatitis C virus (HCV) infection.nnnDATA SOURCESnMEDLINE (1947 to January 2013), the Cochrane Library, and reference lists.nnnSTUDY SELECTIONnStudies that compared the diagnostic accuracy of blood tests with that of liver biopsy.nnnDATA EXTRACTIONnInvestigators abstracted and checked study details and quality by using predefined criteria.nnnDATA SYNTHESISn172 studies evaluated diagnostic accuracy. For identifying clinically significant fibrosis, the platelet count, age-platelet index, aspartate aminotransferase-platelet ratio index (APRI), FibroIndex, FibroTest, and Forns index had median positive likelihood ratios of 5 to 10 at commonly used cutoffs and areas under the receiver-operating characteristic curve (AUROCs) of 0.70 or greater (range, 0.71 to 0.86). For identifying cirrhosis, the platelet count, age-platelet index, APRI, and Hepascore had median positive likelihood ratios of 5 to 10 and AUROCs of 0.80 or greater (range, 0.80 to 0.91). The Göteborg University Cirrhosis Index and the Lok index had slightly lower positive likelihood ratios (4.8 and 4.4, respectively). In direct comparisons, the APRI was associated with a slightly lower AUROC than the FibroTest for identifying fibrosis and a substantially higher AUROC than the aspartate aminotransferase-alanine aminotransferase ratio for identifying fibrosis or cirrhosis.nnnLIMITATIONnOnly English-language articles were included, and most studies had methodological limitations, including failure to describe blinded interpretation of liver biopsy specimens and inadequate description of enrollment methods.nnnCONCLUSIONnMany blood tests are moderately useful for identifying clinically significant fibrosis or cirrhosis in HCV-infected patients.nnnPRIMARY FUNDING SOURCEnAgency for Healthcare Research and Quality.

Opioid Pharmacotherapy for Chronic Non-Cancer Pain in the United States: A Research Guideline for Developing an Evidence-Base

UNLABELLEDnThis document reports the consensus of an interdisciplinary panel of research and clinical experts charged with reviewing the use of opioids for chronic noncancer pain (CNCP) and formulating guidelines for future research. Prescribing opioids for chronic noncancer pain has recently escalated in the United States. Contrasting with increasing opioid use are: 1) The lack of evidence supporting long-term effectiveness; 2) Escalating misuse of prescription opioids including abuse and diversion; and 3) Uncertainty about the incidence and clinical salience of multiple, poorly characterized adverse drug events (ADEs) including endocrine dysfunction, immunosuppression and infectious disease, opioid-induced hyperalgesia and xerostomia, overdose, falls and fractures, and psychosocial complications. Chief among the limitations of current evidence are: 1) Sparse evidence on long-term opioid effectiveness in chronic pain patients due to the short-term time frame of clinical trials; 2) Insufficiently comprehensive outcome assessment; and 3) Incomplete identification and quantification of ADEs. The panel called for a strategic interdisciplinary approach to the problem domain in which basic scientists and clinicians cooperate to resolve urgent issues and generate a comprehensive evidence base. It offered 4 recommendations in 3 areas: 1) A research strategy for studying the effectiveness of long-term opioid pharmacotherapy; 2) Improvements in evidence-generation methodology; and 3) Potential research topics for generating new evidence.nnnPERSPECTIVEnPrescribing opioids for CNCP has outpaced the growth of scientific evidence bearing on the benefits and harms of these interventions. The need for a strong evidence base is urgent. This guideline offers a strategic approach to creating a comprehensive evidence base to guide safe and effective management of CNCP.

AHRQ Series Paper 4: Assessing harms when comparing medical interventions: AHRQ and the Effective Health-Care Program

Comparative effectiveness reviews (CERs) are systematic reviews that evaluate evidence on alternative interventions to help clinicians, policy makers, and patients make informed treatment choices. Reviews should assess harms and benefits to provide balanced assessments of alternative interventions. Identifying important harms of treatment and quantifying the magnitude of any risks require CER authors to consider a broad range of data sources, including randomized controlled trials (RCTs) and observational studies. This may require evaluation of unpublished data in addition to published reports. Appropriate synthesis of harms data must also consider issues related to evaluation of rare or uncommon events, assessments of equivalence or noninferiority, and use of indirect comparisons. This article presents guidance for evaluating harms when conducting and reporting CERs. We include suggestions for prioritizing harms to be evaluated, use of terminology related to reporting of harms, selection of sources of evidence on harms, assessment of risk of bias (quality) of harms reporting, synthesis of evidence on harms, and reporting of evidence on harms.

Core competencies for pain management: Results of an interprofessional consensus summit

Objective The objective of this project was to develop core competencies in pain assessment and management for prelicensure health professional education. Such core pain competencies common to all prelicensure health professionals have not been previously reported. Methods An interprofessional executive committee led a consensus-building process to develop the core competencies. An in-depth literature review was conducted followed by engagement of an interprofessional Competency Advisory Committee to critique competencies through an iterative process. A 2-day summit was held so that consensus could be reached. Results The consensus-derived competencies were categorized within four domains: multidimensional nature of pain, pain assessment and measurement, management of pain, and context of pain management. These domains address the fundamental concepts and complexity of pain; how pain is observed and assessed; collaborative approaches to treatment options; and application of competencies across the life span in the context of various settings, populations, and care team models. A set of values and guiding principles are embedded within each domain. Conclusions These competencies can serve as a foundation for developing, defining, and revising curricula and as a resource for the creation of learning activities across health professions designed to advance care that effectively responds to pain.

Initial highly-active antiretroviral therapy with a protease inhibitor versus a non-nucleoside reverse transcriptase inhibitor: discrepancies between direct and indirect meta-analyses

BACKGROUNDnThe optimum treatment choice between initial highly-active antiretroviral therapy (HAART) with a protease inhibitor (PI) versus a non-nucleoside reverse transcriptase inhibitor (NNRTI) is uncertain. An indirect analysis reported that PI-based HAART was better than NNRTI-based HAART. However, direct evidence for competing interventions is deemed more reliable than indirect evidence for making treatment decisions. We did a meta-analysis of head-to-head trials and compared the results with those of indirect analyses.nnnMETHODSn12 trials of at least 24 weeks duration directly compared NNRTI-based versus PI-based HAART in HIV-infected patients with limited or no previous exposure to antiretrovirals. We also identified six trials of NNRTI-based HAART and eight trials of PI-based HAART, each versus two NRTI regimens. We analysed the outcomes of virological suppression, death or disease progression, and withdrawals due to adverse events.nnnFINDINGSnIn the direct meta-analysis, NNRTI-based regimens were better than PI-based regimens for virological suppression (OR 1.60, 95% CI 1.31-1.96). The difference was reduced in higher-quality trials, but still favoured NNRTI-based HAART. There were no differences in death or disease progression (0.87, 0.56-1.35) or withdrawal because of adverse events (0.68, 0.43-1.08). By contrast, in indirect analyses NNRTI-based HAART was worse than PI-based HAART for virological suppression (0.26, 0.07-0.91). There were no significant differences for death or disease progression (1.28, 0.56-2.94) and withdrawals because of adverse events (1.46, 0.66-3.24). When trials of delavirdine were excluded, similar results were produced.nnnINTERPRETATIONnResults from direct analyses suggested that NNRTI-based HAART was more effective than PI-based HAART for virological suppression and was similar to PI-based HAART for clinical outcomes. Indirect comparisons could be unreliable for complex and rapidly evolving interventions such as HAART.