The pathway to RCTs: how many roads are there? Examining the homogeneity of RCT justification.

BACKGROUND: Randomized controlled trials (RCTs) form the foundational background of modern medical practice. They are considered the highest quality of evidence, and their results help inform decisions concerning drug development and use, preventive therapies, and screening programs. However, the inputs that justify an RCT to be conducted have not been studied. METHODS: We reviewed the MEDLINE and EMBASE databases across six specialties (Ophthalmology, Otorhinolaryngology (ENT), General Surgery, Psychiatry, Obstetrics-Gynecology (OB-GYN), and Internal Medicine) and randomly chose 25 RCTs from each specialty except for Otorhinolaryngology (20 studies) and Internal Medicine (28 studies). For each RCT, we recorded information relating to the justification for conducting RCTs such as average study size cited, number of studies cited, and types of studies cited. The justification varied widely both within and between specialties. RESULTS: For Ophthalmology and OB-GYN, the average study sizes cited were around 1100 patients, whereas they were around 500 patients for Psychiatry and General Surgery. Between specialties, the average number of studies cited ranged from around 4.5 for ENT to around 10 for Ophthalmology, but the standard deviations were large, indicating that there was even more discrepancy within each specialty. When standardizing by the sample size of the RCT, some of the discrepancies between and within specialties can be explained, but not all. On average, Ophthalmology papers cited review articles the most (2.96 studies per RCT) compared to less than 1.5 studies per RCT for all other specialties. CONCLUSIONS: The justifications for RCTs vary widely both within and between specialties, and the justification for conducting RCTs is not standardized.

Correction: Summary of Glaucoma Diagnostic Testing Accuracy: An Evidence-Based Meta-Analysis.

[This corrects the article DOI: 10.14740/jocmr2643w.].

Systemic Immunosuppression in High-Risk Penetrating Keratoplasty: A Systematic Review.

Cornea transplantation has a high success rate and typically only requires topical immunomodulation. However, in high-risk cases, systemic immunosuppression can be used. We conducted a systematic review on the efficacy and side effects of systemic immunosuppression for high-risk cornea transplantation. The study population was 18 years old or older with a high-risk transplant (two or more clock hours of cornea vascularization or a previous failed graft or a graft needed because of herpes simplex keratitis). A comprehensive search strategy was performed with the help of an information specialist and content experts from ophthalmology. All study designs were accepted for assessment. Level 1 and level 2 screening was performed by two reviewers followed by data abstraction. Forest plots were created whenever possible to synthesize treatment effects. Quality assessment was done with a Downs and Blacks score. From 1,150 articles, 29 were ultimately used for data abstraction. The odds ratios (ORs) for clear graft survival in cyclosporine and controls were 2.43 (95% CI: 1.00 - 5.88) and 3.64 (95% CI: 1.48 - 8.91) for rejection free episodes. Mycophenolate mofetil (MMF) significantly improved the rejection free graft survival rates at 1 year (OR: 4.05, 95% CI: 1.83 - 8.96). The overall results suggested that both systemic cyclosporine and MMF improved 1-year rejection free graft survival in high-risk keratoplasty. Cyclosporine also significantly improved clear graft survival rates at 1 year; however, there were insufficient data to analyze the same in the MMF group. Higher quality studies are needed to understand this issue better.

Diabetic retinopathy screening with pharmacy-based teleophthalmology in a semiurban setting: a cost-effectiveness analysis.

BACKGROUND: Diabetic eye complications are the leading cause of visual loss among working-aged people. Pharmacy-based teleophthalmology has emerged as a possible alternative to in-person examination that may facilitate compliance with evidence-based recommendations and reduce barriers to specialized eye care. The objective of this study was to estimate the cost-effectiveness of mobile teleophthalmology screening compared with in-person examination (primary care) for the diabetic population residing in semiurban areas of southwestern Ontario. METHODS: A decision tree was constructed to compare in-person examination (comparator program) versus pharmacy-based teleophthalmology (intervention program). The economic model was designed to identify patients with more than minimal diabetic retinopathy, manifested by at least 1 microaneurysm at examination (modified Airlie House classification grade of ≥ 20). Cost-effectiveness was assessed as cost per case detected (true-positive result) and cost per case correctly diagnosed (including true-positive and true-negative results). RESULTS: The cost per case detected was $510 with in-person examination and $478 with teleophthalmology, and the cost per case correctly diagnosed was $107 and $102 respectively. The incremental cost-effectiveness ratio was $314 per additional case detected and $73 per additional case correctly diagnosed. Use of pharmacologic dilation and health care specialists' fees were the most important cost drivers. INTERPRETATION: The study showed that a compound teleophthalmology program in a semiurban community would be more effective but more costly than in-person examination. The findings raise the question of whether the benefits of pharmacy-based teleophthalmology in semiurban areas, where in-person examination is still available, are equivalent to those observed in remote communities. Further study is needed to investigate the impact of this program on the prevention of severe vision loss and quality of life in a semiurban setting.

Summary of Glaucoma Diagnostic Testing Accuracy: An Evidence-Based Meta-Analysis.

BACKGROUND: New glaucoma diagnostic technologies are penetrating clinical care and are changing rapidly. Having a systematic review of these technologies will help clinicians and decision makers and help identify gaps that need to be addressed. This systematic review studied five glaucoma technologies compared to the gold standard of white on white perimetry for glaucoma detection. METHODS: OVID(®) interface: MEDLINE(®) (In-Process & Other Non-Indexed Citations), EMBASE(®), BIOSIS Previews(®), CINAHL(®), PubMed, and the Cochrane Library were searched. A gray literature search was also performed. A technical expert panel, information specialists, systematic review method experts and biostatisticians were used. A PRISMA flow diagram was created and a random effect meta-analysis was performed. RESULTS: A total of 2,474 articles were screened. The greatest accuracy was found with frequency doubling technology (FDT) (diagnostic odds ratio (DOR): 57.7) followed by blue on yellow perimetry (DOR: 46.7), optical coherence tomography (OCT) (DOR: 41.8), GDx (DOR: 32.4) and Heidelberg retina tomography (HRT) (DOR: 17.8). Of greatest concern is that tests for heterogeneity were all above 50%, indicating that cutoffs used in these newer technologies were all very varied and not uniform across studies. CONCLUSIONS: Glaucoma content experts need to establish uniform cutoffs for these newer technologies, so that studies that compare these technologies can be interpreted more uniformly. Nevertheless, synthesized data at this time demonstrate that amongst the newest technologies, OCT has the highest glaucoma diagnostic accuracy followed by GDx and then HRT.

Graft rejection rate and graft failure rate of penetrating keratoplasty (PKP) vs lamellar procedures: a systematic review.

PURPOSE: The aim of our investigation was to conduct a quantitative meta-analysis of the present world literature comparing the major surgical outcomes of penetrating keratoplasty (PKP) to lamellar procedures. Our goal is that clinicians, eye bank administrators, and health policy makers will be able to utilize this study in implementing decisions in regards to corneal transplantation. METHODS: Pooled measures of association were with odds ratios and because of study heterogeneity, the pooled effects were assumed to follow a random effects model (DerSimonian-Laird). The comparisons were between 1) PKP's and all lamellar procedures (anterior AND posterior) and then 2) between PKP's and all anterior lamellar procedures and 3) PKP and all posterior lamellar procedures. RESULTS: For PKP vs anterior lamellar procedures, the pooled odds ratio for rejection of PKP over lamellar keratoplasty (LK) was 3.56 (95% CI: 1.76-7.20) and for outright failure, the pooled odds ratio of PKP failure vs LK was 2.85 (95% CI: 0.84-9.66). For posterior lamellar procedures, the pooled odds ratio for rejection of PKP over LK was 1.52 (95% CI: 1.00-2.32). The pooled odds ratio for outright failure of PKP over posterior lamellar procedures was 2.09 (95% CI: 0.57-7.59). The follow up time was significantly longer for full transplants than for lamellar procedures. CONCLUSIONS: For both anterior and posterior lamellar procedures, the odds ratios comparing rejection of full transplants to lamellar procedures (both anterior and posterior individually) were significantly higher in the PKP group. For outright failure, the PKP group also had a higher risk of failure than the lamellar groups but this was not statistically significant in either instance (anterior or posterior). Some of the clinical differences benefitting lamellar procedures may at least be partly explained by follow up time differences between groups and this needs to be accounted for more rigorously in future studies.

A randomized clinical trial of selective laser trabeculoplasty versus argon laser trabeculoplasty in patients with pseudoexfoliation.

PURPOSE: To evaluate the efficacy of selective laser trabeculoplasty (SLT) versus argon laser trabeculoplasty (ALT) in lowering the intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension secondary to pseudoexfoliation. DESIGN: Multicentered randomized clinical trial. PARTICIPANTS: A total of 76 eyes from 60 patients with pseudoexfoliation and uncontrolled IOP were recruited from 5 Canadian academic institutions. Patients with prior laser trabeculoplasty, ocular surgery within 6 months, previous glaucoma surgery, an advanced visual field defect, current steroid use, and monocular patients were excluded. METHODS: Eyes were randomized to receive either 180-degree SLT or 180-degree ALT by a nonblocked randomization schedule stratified by center. MAIN OUTCOME MEASUREMENT: The primary outcome was the change in IOP at 6 months versus baseline and secondary outcomes included change in number of glaucoma medications after laser. Baseline variables included age, sex, angle grade, angle pigmentation, and number of glaucoma medications. RESULTS: Of the 76 eyes, 45 eyes received SLT and 31 eyes received ALT. The overall age was 72.9 years (65% females). The baseline IOPs in the SLT and ALT groups were 23.1 and 25.2 mm Hg, respectively (P=0.03). The IOP reduction 6 months after SLT was -6.8 mm Hg and post-ALT was -7.7 mm Hg (P>0.05). The SLT group had reduced glaucoma medications by 0.16 medications at 6 months and the ALT group had no decrease in medications over the same time period (P=0.59). There were no postlaser IOP spikes in either group. DISCUSSION: ALT and SLT are equivalent in lowering IOP at 6 months posttreatment in patients with PXF.

A systematic review and cost-effectiveness analysis of tonometer disinfection methods.

OBJECTIVE: The Goldmann applanation tonometer presents the problem of being one of the most widely used pieces of equipment in the ophthalmic clinic and a known risk factor for the transmission of epidemic keratoconjunctivitis (EKC). The purpose of this review is to assess the effectiveness of 3 methods of disinfection: alcohol swabs, immersion in peroxide, and the use of disposable prisms. An economic evaluation is undertaken to assess the cost-effectiveness of the 3 alternatives. In doing so, we contribute an evidence-based overview of the issue at an opportune time, because several jurisdictions are developing protocols regarding tonometer tip disinfection. DESIGN: Systematic review and cost-effectiveness analysis. METHODS: A comprehensive literature review was undertaken with a librarian, comprising searches of 6 electronic databases and hand searches of the grey literature. A 3-level screening process was undertaken by 2 reviewers according to prespecified inclusion and exclusion criteria. Values from included papers were used to inform a cost-effectiveness analysis undertaken using a decision tree model implemented in TreeAge. The analysis was undertaken from the hospital perspective and included all equipment and labour costs. RESULTS: Synthesis of in vitro data indicates that all 3 methods are plausible methods of disinfection with a 64% reduction in log growth of EKC when peroxide is used compared with alcohol swabs. The incremental cost-effective ratios from the cost-effectiveness analysis were $12,000/case averted using peroxide and $61,000/case averted with Tonosafe as compared with alcohol. CONCLUSIONS: Assuming clinical infection rates match in vitro disinfection data, the cost of bleach is high and the cost of Tonosafe is unacceptably high to reduce 1 potential case of adenoviral keratoconjunctivitis.

Immediately sequential bilateral cataract surgery: a cost-effective procedure.

OBJECTIVE: The objective of this project was to perform a cost-effectiveness analysis (CEA) of immediately sequential bilateral cataract surgery (ISBCS) versus delayed sequential bilateral cataract surgery (DSBCS) to determine whether ISBCS represents an appropriate, cost-effective way to rapidly rehabilitate a patient's visual impairment. DESIGN: A systematic review followed by a primary economic analysis with computer-based econometric modeling. PARTICIPANTS: Not applicable. METHODS: We constructed a decision analytic model from the perspective of the public third-party payer (i.e., the Ministry of Health) to conduct a CEA of both surgeries, ISBCS and DSBCS. Cost data consisted of the costs of the surgery, intravitreal injections, medications, and drops, all of which were obtained from a comprehensive literature search and from records at St. Joseph's Hospital, London, Ont. The effectiveness was measured by the utility values associated with visual acuity in the better seeing eye. RESULTS: ISBCS resulted in an incremental effectiveness of 0.08 utility at an incremental cost of $1607. Discounting the quality-adjusted life-years (QALYs) gained by an annual interest rate of 3% resulted in 0.932 QALYs gained. The cost-effectiveness of ISBCS was calculated to be $1431 per QALY gained. A 1-way sensitivity analysis was performed by varying costs, utility values, probabilities, and discounting rates. This analysis varied the incremental cost-effectiveness ratio but did not change the conclusion. CONCLUSIONS: Health economics assessment showed that, compared with DSBCS, ISBCS is a cost-effective procedure. This finding will be highly useful to policy-makers, decision-makers, clinicians, hospital administrators, and payers in making cost-efficient decisions.

An investigation of the relationship between cataract surgery wait times and rates of surgery.

OBJECTIVE: The relationship between cataract surgery wait times and rates of surgery was investigated to determine whether wait times correlate with rates of surgery. DESIGN: Cross-sectional study. PARTICIPANTS: We collected 2 Ontario registries for cataract surgeries: (i) Cancer Care Ontario wait time registry; and (ii) The Ontario Health Insurance Plan billing records. METHODS: Both registries were used to determine whether wait times correlated with rates of surgery, and the data were then stratified by region of the province, priority (severity) of cases, age, and sex. RESULTS: The total number of surgeries performed between April 2, 2007, and March 31, 2008, was 65,520. The overall mean number of wait days was 69.8 days; the mean patient age was 72.5 years; and the surgery rate was 540.3 per 100,000 members of the population. For high-priority cases (priorities 1 and 2), there was a very weak inverse correlation (p = -0.27 and -0.21) between wait time and surgery rate, whereas the overall correlation between wait time and surgical rate was close to zero in both databases, regardless of the region, the patients' ages, and the patients' genders. CONCLUSIONS: This study demonstrates a very weak correlation between wait times for and rates of cataract surgery, and this should be a concern for policy makers. Further study is needed to see whether this null relationship persists over time and whether it exists for other monitored wait time procedures. Reasons for this null relationship will have to be determined and remedied as the use of wait times becomes a more widespread outcome in Canadian Healthcare.