Searching for evidence in public health emergencies: a white paper of best practices.

Objectives: Information professionals have supported medical providers, administrators and decision-makers, and guideline creators in the COVID-19 response. Searching COVID-19 literature presented new challenges, including the volume and heterogeneity of literature and the proliferation of new information sources, and exposed existing issues in metadata and publishing. An expert panel developed best practices, including recommendations, elaborations, and examples, for searching during public health emergencies. Methods: Project directors and advisors developed core elements from experience and literature. Experts, identified by affiliation with evidence synthesis groups, COVID-19 search experience, and nomination, responded to an online survey to reach consensus on core elements. Expert participants provided written responses to guiding questions. A synthesis of responses provided the foundation for focus group discussions. A writing group then drafted the best practices into a statement. Experts reviewed the statement prior to dissemination. Results: Twelve information professionals contributed to best practice recommendations on six elements: core resources, search strategies, publication types, transparency and reproducibility, collaboration, and conducting research. Underlying principles across recommendations include timeliness, openness, balance, preparedness, and responsiveness. Conclusions: The authors and experts anticipate the recommendations for searching for evidence during public health emergencies will help information specialists, librarians, evidence synthesis groups, researchers, and decision-makers respond to future public health emergencies, including but not limited to disease outbreaks. The recommendations complement existing guidance by addressing concerns specific to emergency response. The statement is intended as a living document. Future revisions should solicit input from a broader community and reflect conclusions of meta-research on COVID-19 and health emergencies.

How well do search filters perform in identifying economic evaluations in MEDLINE and EMBASE.

OBJECTIVES: Health technology assessment (HTA) agencies assessing the cost-effectiveness of healthcare technologies seek evidence from economic evaluations. As well as searching economic evaluation databases, researchers often search MEDLINE and EMBASE, using search filters whose current performance is unclear. We assessed the performance of search filters in identifying economic evaluations from MEDLINE and EMBASE. METHODS: A gold standard of economic evaluations was compiled from National Health Service Economic Evaluation Database (NHS EED) records for 2000, 2003, and 2006. Corresponding records were retrieved in MEDLINE and EMBASE. Search filters were identified from the InterTASC Information Specialists' SubGroup Web site and from Canadian Agency for Drugs and Technologies in Health (CADTH) Information Services. The sensitivity and precision of search filters in retrieving gold standard records from MEDLINE and EMBASE were tested. RESULTS: A total of 2,070 full economic evaluations were identified from NHS EED. Of these, 1,955 records were available in Ovid MEDLINE and 1,873 were available in Ovid EMBASE. Thirteen MEDLINE and eight EMBASE filters were identified. NHS Quality Improvement Scotland (full and brief filters), the NHS EED and Royle and Waugh filters achieved over 0.99 sensitivity in MEDLINE. NHS Quality Improvement Scotland, CADTH, Royle and Waugh, and NHS EED filters achieved greater than 0.99 sensitivity in EMBASE. Filters demonstrated low precision. CONCLUSIONS: This research provided new performance data on search filters to identify economic evaluations in MEDLINE and EMBASE. It demonstrated that highly sensitive economic evaluation filters are available, but that precision is low, yielding perhaps 5 relevant records per 100 records scanned.

Prostaglandin analogues for ophthalmic use: a cost-effectiveness analysis.

BACKGROUND: The objective of this study was to perform an economic analysis of the cost-effectiveness of prostaglandin analogues for the treatment of increased intraocular pressure (IOP). Prostaglandin analogues for ophthalmic use are more costly than alternative agents for the lowering of IOP. An important policy decision is whether to support continued open listing of these agents or to restrict them to limited use status. METHODS: The cost-effectiveness of prostaglandin analogues was assessed using a decision analytic model. Latanoprost was compared with timolol, dorzolamide, and brimonidine, and travoprost was compared with timolol separately. The effectiveness data used for this economic analysis were the number of millilitres of mercury of IOP reduction compared with baseline and the incidence of adverse events resulting in a withdrawal of the patient from the study. Sensitivity analyses were conducted to assess the robustness of the study results. RESULTS: Compared with latanoprost, dorzolamide was not a cost-effective strategy. Compared with brimonidine, latanoprost provided a higher IOP reduction with an incremental cost-effectiveness ratio of $16.17 (base case), but the additional IOP reduction with latanoprost was obtained at a cost higher than the average cost per millimetre of mercury reduction obtained with brimonidine. Compared with timolol, latanoprost and travoprost had a positive incremental cost-effectiveness ratio of $34.48 and $39.06, respectively. INTERPRETATION: For the first-line treatment of glaucoma and elevated IOP, latanoprost is a more cost-effective strategy than dorzolamide and brimonidine. Latanoprost and travoprost are more effective than timolol but also more expensive. For those for whom timolol is not contraindicated, it would be preferable, from a cost-effectiveness standpoint, to initiate treatment with timolol and reserve the prostaglandin analogues as an alternative treatment or as add-on therapy for patients not achieving a clinical response with timolol. Better treatment compliance associated with these analogues improves their cost-effectiveness.

Meta-analysis of clinical efficacy and bleeding risk with intravenous glycoprotein IIb/IIIa antagonists for percutaneous coronary intervention.

OBJECTIVE: Percutaneous coronary intervention (PCI) has become the most common mode of coronary revascularization. Inhibition of platelet aggregation via glycoprotein (GP) IIb/IIIa receptor blockade significantly reduces the acute ischemic complications associated with PCI, but the risk of bleeding may also be increased with these agents. The purpose of the present study was to provide an up-to-date meta-analysis on the clinical efficacy and safety of intravenous GP IIb/IIIa antagonists in patients undergoing PCI. METHODS: A comprehensive search was undertaken to identify all randomized trials of GP IIb/IIIa antagonists versus control in patients intended to undergo PCI. Medline, Embase, Biosis, HealthStar and hand searches were performed. The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), repeat revascularization, thrombocytopenia and bleeding. OR and their 95% CI were calculated using the random effects model. RESULTS: Twenty-one randomized trials were identified, which together included 23,941 patients. The mortality rate at seven days was 0.33% in the GP IIb/IIa group compared with 0.50% in the control group (OR 0.70, 95% CI 0.29 to 1.68); at 30 days, the mortality rate was 0.83% versus 1.21%, respectively (OR 0.72, 95% CI 0.56 to 0.94); at six months, the mortality rate was 1.92% versus 2.33%, respectively (OR 0.85, 95% CI 0.68 to 1.07); and at one year, the mortality rate was 2.61% versus 3.32%, respectively (OR 0.80, 95% CI 0.64 to 1.00). The number needed to treat at 30 days to save one life was 296. The mortality benefit appeared to dissipate by six months and was of borderline significance at one year. The incidence of MI in the treatment group compared with the control group was reduced at seven days (4.31% versus 6.97%, respectively; OR 0.59, 95% CI 0.46 to 0.75), at 30 days (4.54% versus 6.46% respectively; OR 0.63, 95% CI 0.54 to 0.74) and at six months (5.73% versus 8.29%; OR 0.65, 95% CI 0.55 to 0.77). Repeat revascularization procedures were also significantly lower in the GP IIb/IIIa group compared with the control group at seven days (2.47% versus 4.44%, respectively; OR 0.43, 95% CI 0.29 to 0.84), at 30 days (3.44% versus 5.19%, respectively; OR 0.66, 95% CI 0.56 to 0.77) and at six months (15.21% versus 17.40%, respectively; OR 0.86, 95% CI 0.78 to 0.94). Overall, the composite of death, MI and repeat revascularization was reduced at all time points. An assessment of risk revealed that the incidence of thrombocytopenia (OR 1.41, 95% CI 1.10 to 1.81) and minor bleeding (OR 1.80, 95% CI 1.47 to 2.21), but not major bleeding (OR 1.29, 95 CI 0.98 to 1.68), was significantly increased in the GP IIb/IIIa group versus the control group. CONCLUSIONS: Treatment with GP IIb/IIIa inhibitors in the setting of PCI significantly reduces the rates of 30-day mortality, MI and repeat revascularization procedures. These beneficial effects are achieved at an increased risk of thrombocytopenia and minor bleeding, but not major bleeding.

Clinical efficacy and cost-effectiveness of newborn screening for medium chain acyl-CoA dehydrogenase deficiency using tandem mass spectrometry.

OBJECTIVE: To determine the clinical efficacy and cost-effectiveness of newborn screening for MCADD using tandem mass spectrometry (MS/MS) compared with clinical diagnosis within the Canadian context. DESIGN AND METHODS: A systematic review of the clinical and economic literature was performed. For primary economic analysis, a decision-tree model was built based on the available information, the impact of newborn screening on the health care and the relevant Canadian data. RESULTS: Twenty-one clinical and two economic studies met the selection criteria. Mean incidence of MCADD was approximately 1:16,000. Clinical sensitivity and specificity were 100% and 99.99%, respectively. Screening significantly lowered morbidity and mortality. Both economic studies showed that screening for MCADD using MS/MS was cost-effective if willingness-to-pay was US 50,000 dollars. Our primary economic analysis showed that screening was cost-effective based on the cost-effective threshold of C 20,000 dollars per QALY. CONCLUSION: Screening consumes more resources than no screening but attains better health outcomes.

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.

The current status of autotitrating continuous positive airway pressure systems in the management of obstructive sleep apnea.

BACKGROUND: Autotitrating continuous positive airway pressure (APAP) devices have the potential to address some of the disadvantages of titration and treatment with conventional continuous positive airway pressure (CPAP). Information on the performance of APAP in clinical use is still comparatively limited. OBJECTIVE: To assess the status of APAP devices in the management of obstructive sleep apnea (OSA) by reviewing evidence of their efficacy, effectiveness and costs. METHODS: A systematic search of electronic databases and a review of selected comparative studies on the use of APAP in the diagnosis, titration and treatment of OSA was undertaken. Cost analysis using data applicable to the management of OSA in Edmonton, Alberta was performed. RESULTS: Thirty-three studies met the selection criteria: three on the use of APAP in diagnosing OSA; six on APAP for titration; 14 that considered short-term treatment outcomes; and 10 that addressed longer-term treatment of OSA. In most studies, patients suffering from cardiac, pulmonary and other medical conditions were excluded. Available data suggested some potential for the use of APAP in the diagnosis of OSA, but further validation is needed. In titration, estimated treatment pressures tended to be lower with APAP than with the manual titration of CPAP. Although lower treatment pressures were achieved with APAP, there was no significant difference in clinical outcome measures between APAP and CPAP. Estimates of costs suggested that APAP may provide savings in some scenarios. CONCLUSIONS: APAP shows promise in the management of OSA; however, given the exclusion of some categories of patients from trials of this technology, caution is still required in its use.

Long acting beta2 agonists for stable chronic obstructive pulmonary disease with poor reversibility: a systematic review of randomised controlled trials.

BACKGROUND: The long acting beta2-agonists, salmeterol and formoterol, have been recommended, by some, as first line treatment of stable chronic obstructive pulmonary disease (COPD). We reviewed evidence of efficacy and safety when compared with placebo or anticholinergic agents in patients with poorly reversible COPD. METHODS: After searching MEDLINE, EMBASE, HealthSTAR, BIOSIS Previews, PASCAL, ToxFile, SciSearch, the Cochrane Library, and PubMed, as well as Web sites, selected journals, reference lists, and contacting drug manufacturers, two reviewers independently screened reports of randomised controlled trials of parallel or crossover design lasting four weeks or longer and including patients with a forced expiratory volume in one second (FEV1) < or = 75% of predicted, a ratio of FEV1 to forced vital capacity (FVC) < or = 88% of predicted, and < 15% improvement from baseline FEV1 after a dose of a beta2 agonist. We included trials comparing salmeterol or formoterol with placebo or with ipratropium bromide and reporting one of these outcomes: lung function; exercise capacity; quality of life scores; dyspnea; exacerbations; rescue inhaler use; incidence of tachycardia, hypokalemia, or dry mouth. Two reviewers assessed the quality of included reports using the Jadad scale and allocation concealment, and abstracted data. RESULTS: Twelve trials satisfied our inclusion criteria; eight were high quality (Jadad score >2) and four were low quality (< or = 2). The adequacy of allocation concealment was unclear in all of them. We did not perform a meta-analysis due to differences in trial design and how outcomes were reported.Two trials comparing salmeterol with ipratropium did not detect differences; one trial comparing formoterol and ipratropium described greater improvement with formoterol in morning PEFR (15.3 versus 7.1 l/min, p = 0.040). Of twelve trials comparing long acting beta2 agonists with placebo, six reported no improvement in exercise capacity, eleven reported improvements in FEV1 lung function (one reported no improvement), six reported less rescue inhaler usage (one reported no difference) and five reported improved dyspnea scores (two reported no improvement). Differences in quality of life were detected in one salmeterol trial; however, two salmeterol, and one formoterol trial reported no differences. Adverse effects of interest were not reported. CONCLUSION: In terms of clinical outcomes and safety, we could not find convincing evidence that salmeterol and formoterol have demonstrated advantages to ipratropium, a less expensive drug, for patients with stable COPD and poor reversibility. Compared to placebo, we found evidence of reduced rescue inhaler usage and improved spirometric outcomes without a significant impact on quality of life or exercise capacity.