A meta-epidemiological study on the reported treatment effect of pregabalin in neuropathic pain trials over time.

BACKGROUND: Pregabalin is a drug used to treat neuropathic pain, and its use has increased substantially since 2007. Early trials found a strong treatment effect on pain for post-herpetic neuralgia and diabetic neuropathy. However more recent studies have failed to replicate these results. METHODS: This meta-epidemiological study aimed to assess change in the reported effectiveness of pregabalin in neuropathic pain trials over time, and if a change is present, determine any associated factors. DATA SOURCES: We performed electronic searches for published trials in Medline, Embase and Cochrane Central Register of Controlled Trials databases; and unpublished trials on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australia New Zealand Clinical Trials Registry with no restrictions. STUDY SELECTION: We included randomized, placebo-controlled trials of pregabalin for treatment of neuropathic pain in adults. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted study data: sample size and mean baseline, end-point and change in pain scores with measures of variance, trial end year, publication year, clinical indication, funding source, country of study, treatment duration, treatment dose, mean age and percentage male. PRIMARY OUTCOME MEASURE: We defined treatment effect as the mean difference in pain scores between pregabalin and placebo groups at trial end-point and assessed for change over time using a random-effects meta-regression, adjusted for sample size, indication, treatment duration (weeks) and treatment dose. RESULTS: We included 38 randomized published trials (9038 participants) and found that between 2003 and 2020, the reported treatment effect of pregabalin decreased by 0.4 points (95% CI: 0.3 to 0.6; p<0.001) on an 11-point pain scale per 5-year interval, from 1.3 points (95% CI: 1.0 to 1.5) in trials conducted in 2001-2005, to 0.3 (95% CI: -0.1 to 0.7) in trials conducted in 2016-2020. The reported treatment effect was lower than the minimal clinically important difference (MCID) of 1.7 points across all time periods, doses and most indications and was not found to be associated with study characteristics. CONCLUSIONS: The reported treatment effect or analgesic efficacy of pregabalin from clinical trials has diminished over time. Clinical recommendations may need to be re-evaluated to account for recent evidence and to consider whether pregabalin therapy is indicated.

Cost of investigations during the acute hospital stay following total hip or knee arthroplasty, by complication status.

BACKGROUND: Total hip and total knee arthroplasties are among the most common types of surgery performed in Australia today and are effective treatments for severe osteoarthritis. However, the increasing financial burden on the health system owing to the increasing rates of surgery has led to a growing interest in improving the cost-effectiveness and safety of arthroplasty care. This study was designed to quantify the association between post-operative complications, a major cost driver, and the cost of investigations following total hip or knee arthroplasty. METHODS: This is a prospective cohort study of consecutive patients undergoing primary total hip or knee arthroplasty at an Australian public hospital. We measured the number and cost of imaging and pathology tests performed during the acute hospital stay and used linear regression to quantify the association between complication status and investigation costs. RESULTS: Five hundred patients were included in the analysis. On average, those with complications received more tests, and more expensive tests. The mean combined cost of imaging and pathology tests in patients with no complications was AU$ 187 (SD: 12.0). In comparison, patients with minor complications had a mean additional cost of AU$ 270 (SD: 31.0), and those with major complications had a mean additional cost of AU$ 493 (SD: 54.2) (p < 0.001). CONCLUSIONS: In patients undergoing hip or knee arthroplasty, investigation costs are substantially greater in the presence of either minor or major complications. With growing volumes of total hip and total knee arthroplasties, a potential focus of future research could include optimising investigation practices for patients with and without complications.