Practical applications of rapid review methods in the development of Australian health policy.

Rapid reviews (RRs) are a method of evidence synthesis that can provide robust evidence to support policy decisions in a timely manner. Herein we describe the methods used to conduct RRs and present an illustrative case study to describe how RRs can be used to inform contemporary Australian health policy. The aim of the present study was to explore several important aspects of how RRs can inform decision makers. RRs are conducted within limited time frames of as little as 4 weeks. Policy questions may focus on issues of efficacy, service delivery and service organisation rather than reimbursement of new services, which is better answered by a more comprehensive assessment. RRs use flexible and pragmatic methods, which aim to balance the objectivity and rigour required of the reviews within limited time frames. This flexibility allows for great variation across products with regard to length, depth of analysis and methods used. As a result, RRs can be specifically tailored to address targeted policy questions and are a useful tool in the development of Australian health policy.

Rituximab for rheumatoid arthritis.

BACKGROUND: Rituximab is a selective, B-cell depleting, biologic agent for treating refractory rheumatoid arthritis (RA). It is a chimeric monoclonal antibody targeted against CD 20 that is promoted as therapy for patients who fail to respond to other biologics. There is evidence to suggest that rituximab is effective and well tolerated when used in combination with methotrexate for RA. OBJECTIVES: To evaluate the benefits and harms of rituximab for the treatment of RA. SEARCH METHODS: We conducted a search (until January 2014) in electronic databases (The Cochrane Library, MEDLINE, EMBASE, CINAHL, Web of Science), clinical trials registries, and websites of regulatory agencies. Reference lists from comprehensive reviews were also screened. SELECTION CRITERIA: All controlled trials comparing treatment with rituximab as monotherapy or in combination with any disease modifying anti-rheumatic drug (DMARD) (traditional or biologic) versus placebo or other DMARD (traditional or biologic) in adult patients with active RA. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias and abstracted data from each study. MAIN RESULTS: We included eight studies with 2720 patients. For six studies selection bias could not be evaluated and two studies were considered to have low risk of bias. The level of evidence ranged from low to high, but was rated as moderate for most outcomes. We have prioritised reporting of rituximab (two 1000 mg doses) in combination with methotrexate since this is the approved dose and most commonly used combination. We also reported data on other combinations and doses as supplementary information in the results section of the review.American College of Rheumatology (ACR) 50 response rates were statistically significantly improved with rituximab (two 1000 mg doses) in combination with methotrexate compared with methotrexate alone at 24 to 104 weeks. The RR for achieving an ACR 50 at 24 weeks was 3.3 (95% CI 2.3 to 4.6); 29% of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate achieved the ACR 50 compared to 9% of controls. The absolute treatment benefit (ATB) was 21% (95% CI 16% to 25%) with a number needed to treat (NNT) of 6 (95% CI 4 to 9).At 52 weeks, the RR for achieving clinical remission (Disease Activity Score (DAS) 28 joints < 2.6) with rituximab (two 1000 mg doses) in combination with methotrexate compared with methotrexate monotherapy was 2.4 (95% CI 1.7 to 3.5); 22% of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate achieved clinical remission compared to 11% of controls. The ATB was 11% (95% CI 2% to 20%) with a NNT of 7 (95% CI 4 to 13).At 24 weeks, the RR for achieving a clinically meaningful improvement (CMI) in the Health Assessment Questionnaire (HAQ) (> 0.22) for patients receiving rituximab combined with methotrexate compared to patients on methotrexate alone was 1.6 (95% CI 1.2 to 2.1). The ATB was 24% (95% CI 12% to 36%) with an NNT of 5 (95% CI 3 to 13). At 104 weeks, the RR for achieving a CMI in HAQ (> 0.22) was 1.4 (95% CI 1.3 to 1.6). The ATB was 24% (95% CI 16% to 31%) with a NNT of 5 (95% CI 3 to 7).At 24 weeks, the RR for preventing radiographic progression in patients receiving rituximab (two 1000 mg doses) in combination with methotrexate was 1.2 (95% CI 1.0 to 1.4) compared to methotrexate alone; 70% of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate had no radiographic progression compared to 59% of controls. The ATB was 11% (95% CI 2% to 19%) and the NNT was 10 (95% CI 5 to 57). Similar benefits were observed at 52 to 56 weeks and 104 weeks.Statistically significantly more patients achieved a CMI on the physical and mental components of the quality of life, measured by the Short Form (SF)-36, in the rituximab (two 1000 mg doses) in combination with methotrexate-treated group compared with methotrexate alone at 24 to 52 weeks (RR 2.0, 95% CI 1.1 to 3.4; NNT 4, 95% CI 3 to 8 and RR 1.4, 95% CI 1.1 to 1.9; NNT 8, 95% CI 5 to 19, respectively); 34 and 13 more patients out of 100 showed an improvement in the physical component of the quality of life measure compared to methotrexate alone (95% CI 5% to 84%; 95% CI 7% to 8%, respectively).There was no evidence of a statistically significant difference in the rates of withdrawals because of adverse events or for other reasons (that is, withdrawal of consent, violation, administrative, failure to return) in either group. However, statistically significantly more people receiving the control drug withdrew from the study compared to those receiving rituximab (two 1000 mg doses) in combination with methotrexate at all times (RR 0.40, 95% CI 0.32 to 0.50; RR 0.61, 95% CI 0.40 to 0.91; RR 0.48, 95% CI 0.28 to 0.82; RR 0.58, 95% CI 0.45 to 0.75, respectively). At 104 weeks, 37% withdrew from the control group and 20% withdrew from the rituximab (two 1000 mg doses) in combination with methotrexate group. The absolute risk difference (ARD) was -20% (95% CI -34% to -5%) with a number needed to harm (NNH) of 7 (95% CI 5 to 11).A greater proportion of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate developed adverse events after their first infusion compared to those receiving methotrexate monotherapy and placebo infusions (RR 1.6, 95% CI 1.3 to 1.9); 26% of those taking rituximab plus methotrexate reported more events associated with their first infusion compared to 16% of those on the control regimen with an ARD of 9% (95% CI 5% to 13%) and a NNH of 11 (95% CI 21 to 8). However, no statistically significant differences were noted in the rates of serious adverse events. AUTHORS' CONCLUSIONS: Evidence from eight studies suggests that rituximab (two 1000 mg doses) in combination with methotrexate is significantly more efficacious than methotrexate alone for improving the symptoms of RA and preventing disease progression.

Preoperative skin antiseptics for preventing surgical site infections: what to do?

BACKGROUND: Safe and effective patient preoperative skin antisepsis is recommended to prevent surgical site infections (SSIs), reduce patient morbidity, and reduce systemic costs. However, there is lack of consensus among best practice recommendations regarding the optimal skin antiseptic solution and method of application. METHODS: In 2010 and 2011 the health technology appraisal committee of the Surgery Operational Clinical Network (SOCN), of Alberta Health Services (AHS), conducted an environmental scan to determine the current preoperative skin antisepsis in Alberta, reviewed key publications and existing guidelines, and requested a systematic review from the Canadian Agency for Drugs and Technologies in Health (CADTH). Using this information, and an established protocol for evidence-informed recommendations, the health technology appraisal committee made recommendations that were, in 2012, reviewed and endorsed by the SOCN executive and the AHS-Infection Prevention and Control (IPC) group. RESULTS: The environmental scan revealed practice variation in the types of antiseptic solutions and application methods being used in the 18 Alberta hospitals surveyed. The systematic review suggested that preoperative antiseptic showering reduces skin flora but the effect on SSI rates was inconclusive. While the review found no conclusive evidence to recommend an optimal antiseptic solution or application method, the results of two large randomized controlled trials suggest that chlorhexidine in 70% alcohol is more effective than povidone iodine in the prevention of SSIs. These results and the recommendations from Safer Healthcare Now!, a program of the Canadian Patient Safety Institute (CPSI), were used to inform the recommendations for AHS. These recommendations included abandoning preoperative showering with antiseptics except for special cases (high-risk surgeries such as sternotomies and implants as recommended by IPC) and standardizing skin antiseptic application methods and solution to chlorhexidine (CHG) in 70% alcohol. The exception would be procedures involving the ear, eye, mouth, mucous membranes, neural tissue, infants and emergent trauma cases where povidine iodine should be used. CONCLUSION: Using the best available evidence it was recommended that AHS standardize surgical skin antisepsis to 2% CHG in 70% alcohol as the preferred antiseptic and povidone iodine, as an alternative when CHG is contraindicated, to reduce SSIs, practice variation, and health care costs. Further research is required to determine the optimal skin antiseptic solution to reduce SSIs.

Preoperative skin antiseptic preparations for preventing surgical site infections: a systematic review.

OBJECTIVE: To evaluate the clinical effectiveness of preoperative skin antiseptic preparations and application techniques for the prevention of surgical site infections (SSIs). DESIGN: Systematic review of the literature using Medline, EMBASE, and other databases, for the period January 2001 to June 2011. METHODS: Comparative studies (including randomized and nonrandomized trials) of preoperative skin antisepsis preparations and application techniques were included. Two researchers reviewed each study and extracted data using standardized tables developed before the study. Studies were reviewed for their methodological quality and clinical findings. RESULTS: Twenty studies (n = 9,520 patients) were included in the review. The results indicated that presurgical antiseptic showering is effective for reducing skin flora and may reduce SSI rates. Given the heterogeneity of the studies and the results, conclusions about which antiseptic is more effective at reducing SSIs cannot be drawn. CONCLUSIONS: The evidence suggests that preoperative antiseptic showers reduce bacterial colonization and may be effective at preventing SSIs. The antiseptic application method is inconsequential, and data are lacking to suggest which antiseptic solution is the most effective. Disinfectant products are often mixed with alcohol or water, which makes it difficult to form overall conclusions regarding an active ingredient. Large, well-conducted randomized controlled trials with consistent protocols comparing agents in the same bases are needed to provide unequivocal evidence on the effectiveness of one antiseptic preparation over another for the prevention of SSIs.

Pharmacologic management of neovascular age-related macular degeneration: systematic review of economic evidence and primary economic evaluation.

OBJECTIVE: To examine the economic implications for the Canadian health system of pharmacologic treatment of neovascular age-related macular degeneration (AMD). DESIGN: Systematic review of economic literature and a primary economic evaluation. PARTICIPANTS: Economic literature search identified 392 potentially relevant articles, 12 of which were included for final review. METHODS: Studies were included if they met the following criteria: (i) provision of a summary measure of the trade-off between costs and consequences; (ii) participants of 40 years and older with neovascular AMD; (iii) interventions and comparators: comparison of photodynamic therapy using verteporfin (V-PDT), pegaptanib, bevacizumab, ranibizumab, anecortave acetate, intravitreal triamcinolone, placebo, or clinically relevant combinations; and (iv) outcome reported as an incremental measure of the implication of moving from the comparator to the intervention. The following databases were searched through the OVID interface: MEDLINE, EMBASE, BIOSIS Previews, CINAHL, PubMed, Health Economic Evaluations Database (HEED), and the Cochrane Library. For the economic evaluation, we took a decision analytic approach and modeled a cost-utility analysis, conducting it as a microsimulation of a Markov model. RESULTS: In general, V-PDT is more cost effective than conventional macular laser, and pegaptanib is likely more cost effective than V-PDT. The primary economic analysis revealed ranibizumab to be effective but at an unacceptably high cost per quality-adjusted life year (QALY)(>$50,000 per QALY). CONCLUSIONS: Although ranibizumab is effective for wet AMD, its cost is unacceptably high based on cost-utility theory.

Safety and effectiveness of point-of-care monitoring devices in patients on oral anticoagulant therapy: a meta-analysis.

BACKGROUND: Point-of-care devices (POCDs) for monitoring long-term oral anticoagulation therapy (OAT) may be a useful alternative to laboratory-based international normalized ratio [INR] testing and clinical management. PURPOSE: To determine clinical outcomes of the use of POCDs for OAT management by performing a meta-analysis. Previous meta-analyses on POCDs have serious limitations. DATA SOURCES: PubMed, the Cochrane Library, DIALOG, MEDLINE, EMBASE, BIOSIS Previews and PASCAL databases. STUDY SELECTION: Randomized controlled trials of patients on long-term OAT, comparing anticoagulation monitoring by POCD with laboratory INR testing and clinical management. DATA EXTRACTION: 1) rates of major hemorrhage; 2) rates of major thromboembolic events; 3) percentage of time that the patient is maintained within the therapeutic range; 4) deaths. Outcomes were compared using a random-effects model. Summary measures of rates were determined. The quality of studies was assessed using the Jadad scale. DATA SYNTHESIS: Seventeen articles (16 studies) were included. Data analysis showed that POCD INR testing reduced the risk of major thromboembolic events (odds ratio [OR] = 0.51; 95% confidence interval [CI] 0.35-0.74), was associated with fewer deaths (OR = 0.58; 95% CI = 0.38-0.89), and resulted in better INR control compared with laboratory INR testing. No significant difference between the two management modalities with respect to odds ratios for major hemorrhage was found. LIMITATIONS: Quality scores varied from 1 to 3 (out of a maximum of 5). Only 3 studies defined how thromboembolic events would be diagnosed, casting doubt on the accuracy of the reporting of thromboembolic events. The studies suggest that only 24% of patients are good candidates for self-testing and self-management. Compared with patients managed with laboratory-based monitoring, POCD patients underwent INR testing at a much higher frequency and received much more intensive education on OAT management. CONCLUSIONS: The use of POCDs is safe and may be more effective than laboratory-based monitoring. However, most patients are not good candidates for self-testing and self-management. Patient education and frequency of testing may be the most important factors in successful PODC management. Definitive conclusions about the clinical benefits provided by self-testing and self-management require more rigorously designed trials.

Recommendations and supporting evidence in guidelines for referral of patients to sleep laboratories.

At the request of Canadian health ministries, we reviewed recommendations in guidelines prepared by professional bodies on the referral of individuals to sleep laboratories. Searching electronic databases and the Internet, we found 37 guidelines that covered 18 applications of sleep laboratory investigation including obstructive sleep apnea, other respiratory disorders, obstructive sleep apnea and other conditions in children, sudden infant death syndrome, treatment for snoring, insomnia, depression with insomnia, narcolepsy, restless legs syndrome/periodic limb movement disorder, parasomnias and circadian rhythm disorders. We identified recommendations on referral of patients for sleep studies and assessed the quality and relevance of evidence cited in support of these. Of 81 recommendations, 46 were supported by evidence from primary investigations. Only six cases cited evidence from well-conducted, prospective controlled studies. Evidence was highly relevant in 18 cases, of some relevance in 22 and of little or no relevance in six. No evidence was provided in support of 31 recommendations, and in four cases the guideline had identified an absence of available evidence. Although the publications from professional bodies that were reviewed contain much detailed information, evidence supporting many recommendations is limited. There is a need for further, good quality, studies of many sleep laboratory applications.

Systematic review of economic evidence on stroke rehabilitation services.

OBJECTIVES: Given the resource-intensive nature of stroke rehabilitation, it is important that services be delivered in an evidence-based and cost-efficient manner. The objective of this review was to assess the evidence on the relative cost or cost-effectiveness of three rehabilitation services after stroke: stroke unit care versus care on another hospital ward, early supported discharge (ESD) services versus "usual care," and community or home-based rehabilitation versus "usual care." METHODS: A systematic literature review of cost analyses or economic evaluations was performed. Study characteristics and results (including mean total cost per patient) were summarized. The level of evidence concerning relative cost or cost-effectiveness for each service type was determined qualitatively. RESULTS: Fifteen studies met the inclusion criteria: three on stroke unit care, eight on ESD services, and four on community-based rehabilitation. All were classified as cost-consequences analysis or cost analysis. The time horizon was generally short (1 year or less). The comparators and the scope of costs varied between studies. CONCLUSIONS: There was "some" evidence that the mean total cost per patient of rehabilitation in a stroke unit is comparable to care provided in another hospital ward. There is "moderate" evidence that ESD services provide care at modestly lower total costs than usual care for stroke patients with mild or moderate disability. There was "insufficient" evidence concerning the cost of community-based rehabilitation compared with usual care. Several methodological problems were encountered when analyzing the economic evidence.

Continuous glucose monitoring in the management of diabetes mellitus.

Continuous glucose monitors (CGMs) measure interstitial fluid (ISF) glucose, and provide information about continuous glucose fluctuations that is not otherwise captured by intermittent blood glucose testing. CGMs may benefit patients having difficulty controlling their blood sugar or during initiation or monitoring of insulin pump use. CGMs require calibration with finger-stick tests and supplement, but do not replace conventional blood glucose testing. CGM values correspond to blood glucose values taken approximately 13-18 minutes earlier and may differ from metered readings.