Measuring the Monetary Value of Dental Implants for Denture Retention: A Willingness to Pay Approach

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Use of surrogate endpoints in healthcare policy : proposal for consistent adoption of a validation framework

We propose a three step framework for the evaluation of surrogate endpoints for health policy decisions on health technologies

Abstracts in high profile journals often fail to report harm

<p>Abstract</p> <p>Background</p> <p>To describe how frequently harm is reported in the abstract of high impact factor medical journals.</p> <p>Methods</p> <p><it>Design and population</it>: We carried out a blinded structured review of a random sample of 363 Randomised Controlled Trials (RCTs) carried out on human beings, and published in high impact factor medical journals in 2003. <it>Main endpoint</it>: 1) Proportion of articles reporting harm in the abstract; and 2) Proportion of articles that reported harm in the abstract when harm was reported in the main body of the article. <it>Analysis</it>: Corrected Prevalence Ratio (cPR) and its exact confidence interval were calculated. Non-conditional logistic regression was used.</p> <p>Results</p> <p>363 articles and 407 possible comparisons were studied. Overall, harm was reported in 135 abstracts [37.2% (CI95%:32.2 to 42.4)]. Harm was reported in the main text of 243 articles [66.9% (CI95%: 61.8 to 71.8)] and was statistically significant in 54 articles [14.9% (CI95%: 11.4 to 19.0)]. Among the 243 articles that mentioned harm in the text, 130 articles [53.5% (CI95% 47.0 to 59.9)] reported harm in the abstract; a figure that rose to 75.9% (CI95%: 62.4 to 86.5) when the harm reported in the text was statistically significant. Harm in the abstract was more likely to be reported when statistically significant harm was reported in the main body of the article [cPR = 1.70 (CI95% 1.47 to 1.92)] and when drug companies (not public institutions) funded the RCTs [cPR = 1.29 (CI95% 1.03 to 1.67)].</p> <p>Conclusion</p> <p>Abstracts published in high impact factor medical journals underreport harm, even when harm is reported in the main body of the article.</p

Estimating the Power of Indirect Comparisons: A Simulation Study

Indirect comparisons are becoming increasingly popular for evaluating medical treatments that have not been compared head-to-head in randomized clinical trials (RCTs). While indirect methods have grown in popularity and acceptance, little is known about the fragility of confidence interval estimations and hypothesis testing relying on this method.We present the findings of a simulation study that examined the fragility of indirect confidence interval estimation and hypothesis testing relying on the adjusted indirect method.Our results suggest that, for the settings considered in this study, indirect confidence interval estimation suffers from under-coverage while indirect hypothesis testing suffers from low power in the presence of moderate to large between-study heterogeneity. In addition, the risk of overestimation is large when the indirect comparison of interest relies on just one trial for one of the two direct comparisons.Indirect comparisons typically suffer from low power. The risk of imprecision is increased when comparisons are unbalanced

Accuracy of drug advertisements in medical journals under new law regulating the marketing of pharmaceutical products in Switzerland

<p>Abstract</p> <p>Background</p> <p>New legal regulations for the marketing of pharmaceutical products were introduced in 2002 in Switzerland. We investigated whether claims in drug advertisements citing published scientific studies were justified by these studies after the introduction of these new regulations.</p> <p>Methods</p> <p>In this cross-sectional study, two independent reviewers screened all issues of six major Swiss medical journals published in the year 2005 to identify all drug advertisements for analgesic, gastrointestinal and psychopharmacologic drugs and evaluated all drug advertisements referring to at least one publication. The pharmaceutical claim was rated as being supported, being based on a potentially biased study or not to be supported by the cited study according to pre-specified criteria. We also explored factors likely to be associated with supported advertisement claims.</p> <p>Results</p> <p>Of 2068 advertisements 577 (28%) promoted analgesic, psychopharmacologic or gastrointestinal drugs. Among them were 323 (56%) advertisements citing at least one reference. After excluding multiple publications of the same drug advertisement and advertisements with non-informative references, there remained 29 unique advertisements with at least one reference to a scientific study. These 29 advertisements contained 78 distinct pairs of claims of analgesic, gastrointestinal and psychopharmacologic drugs and referenced studies. Thirty-seven (47%) claims were supported, 16 (21%) claims were not supported by the corresponding reference, and 25 (32%) claims were based on potentially biased evidence, with no relevant differences between drug groups. Studies with conflict of interest and studies stating industry funding were more likely to support the corresponding claim (RR 1.52, 95% CI 1.07–2.17 and RR 1.50, 95% CI 0.98–2.28) than studies without identified conflict of interest and studies without information on type of funding.</p> <p>Conclusion</p> <p>Following the introduction of new regulations for drug advertisement in Switzerland, 53% of all assessed pharmaceutical claims published in major medical journals are not supported by the cited referenced studies or based on potentially biased study information. In light of the discrepancy between the new legislation and the endorsement of these regulations, physicians should not trust drug advertisement claims even when they seem to refer to scientific studies.</p

Antiretroviral pill count and clinical outcomes in treatment-naive patients with HIV infection

Objectives: Treatment guidelines recommend single-tablet regimens for patients with HIV infection starting antiretroviral therapy. These regimens might be as effective and cost less if taken as separate drugs. We assessed whether the one pill once a day combination of efavirenz, emtricitabine and tenofovir reduces the risk of disease progression compared with multiple-pill formulations of the same regimen. Methods: We selected treatment-naïve patients starting one-, two- or three-pill formulations of this regimen in data from the Antiretroviral Therapy Cohort Collaboration. These patients were followed until an AIDS event or death or until they modified their regimen. We analysed these data using Cox regression models, then used our models to predict the potential consequences of exposing a future population to either a one-pill regimen or a three-pill regimen. Results: Among 11 739 treatment-naïve patients starting the regimen, there were 386 AIDS events and 87 deaths. Follow-up often ended when patients switched to the same regimen with fewer pills. After the first month, two pills rather than one was associated with an increase in the risk of AIDS or death [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.01-1.91], but three pills rather than two did not appreciably add to that increase (HR 1.19; 95% CI 0.84-1.68). We estimate that 77 patients would need to be exposed to a one-pill regimen rather than a three-pill regimen for 1 year to avoid one additional AIDS event or death. Conclusions: This particular single-tablet regimen is associated with a modest decrease in the risk of AIDS or death relative to multiple-pill formulations

Fine mapping of genetic polymorphisms of pulmonary tuberculosis within chromosome 18q11.2 in the Chinese population: a case-control study

<p>Abstract</p> <p>Background</p> <p>Recently, one genome-wide association study identified a susceptibility locus of rs4331426 on chromosome 18q11.2 for tuberculosis in the African population. To validate the significance of this susceptibility locus in other areas, we conducted a case-control study in the Chinese population.</p> <p>Methods</p> <p>The present study consisted of 578 cases and 756 controls. The SNP rs4331426 and other six tag SNPs in the 100 Kbp up and down stream of rs4331426 on chromosome 18q11.2 were genotyped by using the Taqman-based allelic discrimination system.</p> <p>Results</p> <p>As compared with the findings from the African population, genetic variation of the SNP rs4331426 was rare among the Chinese. No significant differences were observed in genotypes or allele frequencies of the tag SNPs between cases and controls either before or after adjusting for age, sex, education, smoking, and drinking history. However, we observed strong linkage disequilibrium of SNPs. Constructed haplotypes within this block were linked the altered risks of tuberculosis. For example, in comparison with the common haplotype AA_{(rs8087945-rs12456774)}, haplotypes AG_{(rs8087945-rs12456774)}and GA_{(rs8087945-rs12456774)}were associated with a decreased risk of tuberculosis, with the adjusted odds ratio(95% confidence interval) of 0.34(0.27-0.42) and 0.22(0.16-0.29), respectively.</p> <p>Conclusions</p> <p>Susceptibility locus of rs4331426 discovered in the African population could not be validated in the Chinese population. None of genetic polymorphisms we genotyped were related to tuberculosis in the single-point analysis. However, haplotypes on chromosome 18q11.2 might contribute to an individual's susceptibility. More work is necessary to identify the true causative variants of tuberculosis.</p

Response to ‘Re: Kakkos et al. Efficacy and Safety of the New Oral Anticoagulants Dabigatran, Rivaroxaban, Apixaban, and Edoxaban in the Treatment and Secondary Prevention of Venous Thromboembolism: A Systematic Review and Meta-analysis of Phase III Trials’

We estimated and compared the risk of clinically identified acquired drug resistance under immediate initiation [the currently recommended antiretroviral therapy (ART) initiation strategy], initiation with CD4 cell count less than 500 cells/μl and initiation with CD4 cell count less than 350 cells/μl. Cohort study based on routinely collected data from the HIV-CAUSAL collaboration. For each individual, baseline was the earliest time when all eligibility criteria (ART-naive, AIDS free, and others) were met after 1999. Acquired drug resistance was defined using the Stanford classification as resistance to any antiretroviral drug that was clinically identified at least 6 months after ART initiation. We used the parametric g-formula to adjust for time-varying (CD4 cell count, HIV RNA, AIDS, ART regimen, and drug resistance testing) and baseline (calendar period, mode of acquisition, sex, age, geographical origin, ethnicity and cohort) characteristics. In 50 981 eligible individuals, 10% had CD4 cell count more than 500 cells/μl at baseline, and 63% initiated ART during follow-up. Of 2672 tests for acquired drug resistance, 794 found resistance. The estimated 7-year risk (95% confidence interval) of acquired drug resistance was 3.2% (2.8,3.5) for immediate initiation, 3.1% (2.7,3.3) for initiation with CD4 cell count less than 500 cells/μl, and 2.8% (2.5,3.0) for initiation with CD4 cell count less than 350 cells/μl. In analyses restricted to individuals with baseline in 2005-2015, the corresponding estimates were 1.9% (1.8, 2.5), 1.9% (1.7, 2.4), and 1.8% (1.7, 2.2). Our findings suggest that the risk of acquired drug resistance is very low, especially in recent calendar periods, and that immediate ART initiation only slightly increases the risk. It is unlikely that drug resistance will jeopardize the proven benefits of immediate ART initiation