Joseph C. Cappelleri

Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction.

An abridged five-item version of the 15-item International Index of Erectile Function (IIEF) was developed (IIEF-5) to diagnose the presence and severity of erectile dysfunction (ED). The five items selected were based on ability to identify the presence or absence of ED and on adherence to the National Institute of Healths definition of ED. These items focused on erectile function and intercourse satisfaction. For 1152 men (1036 with ED, 116 controls) analyzed, a receiver operating characteristic curve indicated that the IIEF-5 is an excellent diagnostic test. Based on equal misclassification rates of ED and no ED, a cutoff score of 21 (range of scores, 5–25) discriminated best (sensitivity=0.98, specificity=0.88). ED was classified into five severity levels, ranging from none (22–25) through severe (5–7). Substantial agreement existed between the predicted and ‘true’ ED classes (weighted kappa=0.82). These data suggest that the IIEF-5 possesses favorable properties for detecting the presence and severity of ED.

The International Index of Erectile Function (IIEF): a state-of-the-science review

The International Index of Erectile Function (IIEF) is a widely used, multi-dimensional self-report instrument for the evaluation of male sexual function. It is has been recommended as a primary endpoint for clinical trials of erectile dysfunction (ED) and for diagnostic evaluation of ED severity. The IIEF was developed in conjunction with the clinical trial program for sildenafil, and has since been adopted as the ‘gold standard’ measure for efficacy assessment in clinical trials of ED. It has been linguistically validated in 32 languages and used as a primary endpoint in more than 50 clinical trials. This review summarizes early stages in the psychometric validation of the instrument, its subsequent adoption in randomized clinical trials with sildenafil and other ED therapies, and its use in classifying ED severity and prevalence. The IIEF meets psychometric criteria for test reliability and validity, has a high degree of sensitivity and specificity, and correlates well with other measures of treatment outcome. It has demonstrated consistent and robust treatment responsiveness in studies in USA, Europe and Asia, as well as in a wide range of etiological subgroups. Although only one direct comparator trial has been performed to date, the IIEF is also sensitive to therapeutic effects with treatment agents other than sildenafil. A severity classification for ED has recently been developed, in addition to a brief screening version of the instrument. This review includes the strengths as well as limitations of the IIEF, along with some potential areas for future research.

Interpreting Indirect Treatment Comparisons and Network Meta-Analysis for Health-Care Decision Making: Report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: Part 1

Evidence-based health-care decision making requires comparisons of all relevant competing interventions. In the absence of randomized, controlled trials involving a direct comparison of all treatments of interest, indirect treatment comparisons and network meta-analysis provide useful evidence for judiciously selecting the best choice(s) of treatment. Mixed treatment comparisons, a special case of network meta-analysis, combine direct and indirect evidence for particular pairwise comparisons, thereby synthesizing a greater share of the available evidence than a traditional meta-analysis. This report from the ISPOR Indirect Treatment Comparisons Good Research Practices Task Force provides guidance on the interpretation of indirect treatment comparisons and network meta-analysis to assist policymakers and health-care professionals in using its findings for decision making. We start with an overview of how networks of randomized, controlled trials allow multiple treatment comparisons of competing interventions. Next, an introduction to the synthesis of the available evidence with a focus on terminology, assumptions, validity, and statistical methods is provided, followed by advice on critically reviewing and interpreting an indirect treatment comparison or network meta-analysis to inform decision making. We finish with a discussion of what to do if there are no direct or indirect treatment comparisons of randomized, controlled trials possible and a health-care decision still needs to be made.

Conducting indirect-treatment-comparison and network-meta-analysis studies: Report of the ISPOR task force on indirect treatment comparisons good research practices: Part 2

Evidence-based health care decision making requires comparison of all relevant competing interventions. In the absence of randomized controlled trials involving a direct comparison of all treatments of interest, indirect treatment comparisons and network meta-analysis provide useful evidence for judiciously selecting the best treatment(s). Mixed treatment comparisons, a special case of network meta-analysis, combine direct evidence and indirect evidence for particular pairwise comparisons, thereby synthesizing a greater share of the available evidence than traditional meta-analysis. This report from the International Society for Pharmacoeconomics and Outcomes Research Indirect Treatment Comparisons Good Research Practices Task Force provides guidance on technical aspects of conducting network meta-analyses (our use of this term includes most methods that involve meta-analysis in the context of a network of evidence). We start with a discussion of strategies for developing networks of evidence. Next we briefly review assumptions of network meta-analysis. Then we focus on the statistical analysis of the data: objectives, models (fixed-effects and random-effects), frequentist versus Bayesian approaches, and model validation. A checklist highlights key components of network meta-analysis, and substantial examples illustrate indirect treatment comparisons (both frequentist and Bayesian approaches) and network meta-analysis. A further section discusses eight key areas for future research.

Single or multiple daily doses of aminoglycosides: a meta- analysis

Abstract Objective: To assess relative efficacy and toxicity of aminoglycosides given by single daily dose compared with multiple daily doses. Design: Meta-analysis of 21 randomised trials identified through MEDLARS (1966 to January 1995). Data were overviewed with fixed effects and random effects models and with meta-regression analysis. Subjects: Total of 3091 patients with bacterial infection, most without pre-existing renal disease. Interventions: Patients were randomised to receive aminoglycosides once daily or multiple times daily with similar total daily dose. Main outcome measures: Clinical failure of treatment, nephrotoxicity, ototoxicity, and mortality. Results: Single daily dose regimen produced a non-significant decrease in risk of antibiotic failures (random effects risk ratio 0.83 (95% confidence interval 0.57 to 1.21)). Benefit of once daily dosing was greater when the percentage of pseudomonas isolates in a trial was larger. Once daily administration reduced risk of nephrotoxicity (fixed effects risk ratio 0.74 (0.54 to 1.00)). Similar trends were noted for patients with febrile neutropenia and for children. There was no significant difference in ototoxicity between the two dosing regimens, but the power of the pooled trials to detect a meaningful difference was low. There was no significant difference in mortality. Conclusions: Once daily administration of aminoglycosides in patients without pre-existing renal impairment is as effective as multiple daily dosing, has a lower risk of nephrotoxicity, and no greater risk of ototoxicity. Given the additional convenience and reduced cost, once daily dosing should be the preferred mode of administration. Key messages Key messages This meta-analysis shows that single daily doses of aminoglycosides were about 25% less nephrotoxic than and at least as effective clinically as multiple daily doses The dosing schedule did not significantly affect the incidence of ototoxicity, but the power to detect a difference was small Once daily dosing was non-significantly more effective in patients with febrile neutropenia and in children, and the apparent benefit of once daily dosing increased with increasing proportion of pseudomonas isolates in a trial Besides the convenience of once daily dosing, reduced costs of drug administration and omission of measurements of peak antibiotic concentrations should result in substantial cost savings

The Sexual Health Inventory for Men (SHIM): a 5-year review of research and clinical experience

The Sexual Health Inventory for Men (SHIM) is a widely used scale for screening and diagnosis of erectile dysfunction (ED) and severity of ED in clinical practice and research. In reviewing the SHIM-related literature, we sought to provide a compendium of studies in which the SHIM was used, to provide a systematic framework for organizing and evaluating the studies, and to provide a status report on the SHIM and its impact on the management of male sexual dysfunction. Using a Medline search, we found that the SHIM was an integral measure in at least 21 studies on the prevalence of ED, 23 studies on the efficacy of ED interventions, and eight other (mainly correlational) studies. The quantity of research and quality of scholarship on the SHIM provide testimony to its positive impact on understanding and improving male sexual function. These scientific contributions are likely to remain influential in coming years.

Minimal Clinically Important Difference in the Fibromyalgia Impact Questionnaire

Objective. The Fibromyalgia Impact Questionnaire (FIQ) is a disease-specific composite instrument that measures the effect of problems experienced by patients with fibromyalgia (FM). Utilization of the FIQ in measuring changes due to interventions in FM requires derivation of a clinically meaningful change for that instrument. Analyses were conducted to estimate the minimal clinically important difference (MCID), and to propose FIQ severity categories. Methods. Data from 3 similarly designed, 3-month placebo-controlled, clinical treatment trials of pregabalin 300, 450, and 600 mg/day in patients with FM were modeled to estimate the change in the mean FIQ total and stiffness items corresponding to each category on the Patient Global Impression of Change. FIQ severity categories were modeled and determined using established pain severity cutpoints as an anchor. Results. A total of 2228 patients, mean age 49 years, 93% women, with a mean baseline FIQ total score of 62 were treated in the 3 studies. Estimated MCID on a given measure were similar across the studies. In a pooled analysis the estimated MCID (95% confidence interval) was 14% (13; 15) and for FIQ stiffness it was 13% (12; 14). In the severity analysis a FIQ total score from 0 to < 39 was found to represent a mild effect, ≥ 39 to < 59 a moderate effect, and ≥ 59 to 100 a severe effect. Conclusion. The analysis indicates that a 14% change in the FIQ total score is clinically relevant, and results of these analyses should enhance the clinical utility of the FIQ in research and practice.

An empirical study of the effect of the control rate as a predictor of treatment efficacy in meta-analysis of clinical trials

If the control rate (CR) in a clinical trial represents the incidence or the baseline severity of illness in the study population, the size of treatment effects may tend to very with the size of control rates. To investigate this hypothesis, we examined 115 meta-analyses covering a wide range of medical applications for evidence of a linear relationship between the CR and three treatment effect (TE) measures: the risk difference (RD); the log relative risk (RR), and the log odds ratio (OR). We used a hierarchical model that estimates the true regression while accounting for the random error in the measurement of and the functional dependence between the observed TE and the CR. Using a two standard error rule of significance, we found the control rate was about two times more likely to be significantly related to the RD (31 per cent) than to the RR (13 per cent) or the OR (14 per cent). Correlations between TE and CR were more likely when the meta-analysis included 10 or more trials and if patient follow-up was less than six months and homogeneous. Use of weighted linear regression (WLR) of the observed TE on the observed CR instead of the hierarchical model underestimated standard errors and overestimated the number of significant results by a factor of two. The significant correlation between the CR and the TE suggests that, rather than merely pooling the TE into a single summary estimate, investigators should search for the causes of heterogeneity related to patient characteristics and treatment protocols to determine when treatment is most beneficial and that they should plan to study this heterogeneity in clinical trials.

Development and validation of the Self-Esteem And Relationship (SEAR) questionnaire in erectile dysfunction

Development and validation of a patient-reported measure of psychosocial variables in men with erectile dysfunction (ED) is described. Literature review, focus groups, and medical specialists identified 86 potential items. Redundant, ambiguous, or low item-to-total correlation items were removed. Data from 98 men reporting diagnosed ED and 94 controls assisted in final item selection and psychometric evaluation. Treatment responsiveness was evaluated in 93 men with ED in a 10-week open-label trial of sildenafil citrate (Viagra®). The 14 chosen items resolved into two domains: Sexual Relationship (eight items) and Confidence (six items), the latter comprising Self-Esteem (four items) and Overall Relationship (two items) subscales. The resulting Self-Esteem And Relationship (SEAR) questionnaire demonstrated validity and reliability. The intervention study demonstrated responsiveness to beneficial treatment with significant improvement in scores (P=0.0001). The SEAR questionnaire possesses strong psychometric properties that support its validity and reliability for measuring sexual relationship, confidence, and particularly self-esteem.

Psychometric analysis of the Three-Factor Eating Questionnaire-R21: results from a large diverse sample of obese and non-obese participants

Background:The 21-item Three-Factor Eating Questionnaire (TFEQ-R21) is a scale that measures three domains of eating behavior: cognitive restraint (CR), uncontrolled eating (UE) and emotional eating (EE).Objectives:To assess the factor structure and reliability of TFEQ-R21 (and if necessary, refine the structure) in diverse populations of obese and non-obese individuals.Design:Data were obtained from obese adults in a United States/Canadian clinical trial (n=1741), and overweight, obese and normal weight adults in a US web-based survey (n=1275). Confirmatory factor analyses were employed to investigate the structure of TFEQ-R21 using baseline data from the clinical trial. The model was refined to obtain adequate fit and internal consistency. The refined model was then tested using the web-based data. Relationships between TFEQ domains and body mass index (BMI) were examined in both populations.Results:Clinical data indicated that TFEQ-R21 needed refinement. Three items were removed from the CR domain, producing the revised version TFEQ-R18V2 (Comparative Fit Index (CFI)=0.91). Testing TFEQ-R18V2 in the web-based sample supported the revised structure (CFI=0.96; Cronbachs coefficient α of 0.78–0.94). Associations with BMI were small. In the clinical study, the CR domain showed a significant and negative association with BMI. On the basis of the web-based survey, it was shown that the relationship between BMI and CR is population-dependent (obese versus non-obese, healthy versus diabetics).Conclusions:In two independent datasets, the TFEQ-R18V2 showed robust factor structure and good reliability. It may provide a useful tool for characterizing UE, CR and EE.