Clinically Important Differences for Mobility Measures Derived from the Testosterone Trials.
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ABSTRACT: Background/objectives
Accurate estimates of clinically important difference (CID) are required for interpreting the clinical importance of treatments to improve physical function, but CID estimates vary in different disease populations. We determined the CID for two common measures of walking ability in mobility-limited older men.Design
Longitudinal, multisite placebo-controlled trial.Setting/participants
Men enrolled in the Testosterone Trials who had self-reported mobility limitation and gait speed less than 1.2 m/second (n = 429). Testosterone- and placebo-allocated participants were combined for this study.Results
Mean changes from baseline, adjusting for time-in-intervention and site, were 29.6, 13.2, 12.5, -2.4, and -32.6 m for 6MWD, and 15.4, 7.2, 2.1, -3.4, and -7.2 for PF10 in men who reported their mobility was "very/much better," "little better," "no change," "little worse," or "much worse," respectively. CID estimates using regression, ROC, and eCDF varied from 5.0-29.6 m for 6MWD, and 5.0-15.2 points for PF10.Conclusion
CID estimates vary by the population studied and by the method and precision of measurement. Increases of 16 to 30 m for 6MWD and 5 to 15 points for PF10 over 12 months appear to be clinically meaningful in mobility-limited, older hypogonadal men. These CID estimates may be useful in the design of efficacy trials of therapies to improve physical function.
SUBMITTER: Stephens-Shields AJ
PROVIDER: S-EPMC8500528 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results. Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and to determine definitively whether testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objective measures of age-associated conditions. Methods We present the scientific and clinical rationale for the decisions made in the design of this set of trials. Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concentrations and symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, common approaches to treatment and monitoring, and the ability to pool safety data. The logistical advantages were a single steering committee, data coordinating center and data and safety monitoring board, the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in participant selection was setting the eligibility criterion for serum testosterone low enough to ensure that the men were unequivocally testosterone deficient, but not so low as to preclude sufficient enrollment or eventual generalizability of the results. The major considerations in choosing primary outcomes for each trial were identifying those of the highest clinical importance and identifying the minimum clinically important differences between treatment arms for sample size estimation. Potential limitations Setting the serum testosterone concentration sufficiently low to ensure that most men would be unequivocally testosterone deficient, as well as many other entry criteria, resulted in screening approximately 30 men in person to randomize one participant. Conclusion Designing The Testosterone Trials as a coordinated set of seven trials afforded many important scientific and logistical advantages but required an intensive recruitment and screening effort.
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Project description:PurposeTo estimate minimally important differences (MIDs) for the Visual Activities Questionnaire (VAQ) and the National Eye Institute-Visual Function Questionnaire (NEI-VFQ).MethodsA total of 607 subjects with newly-diagnosed open-angle glaucoma (OAG) was enrolled in the Collaborative Initial Glaucoma Treatment Study (CIGTS) and randomized to initial treatment with medications or surgery. Subjects underwent an ophthalmic examination and telephone-administered quality of life (QOL) interview before randomization and every six months thereafter. The VAQ and NEI-VFQ were used to assess participants' perceptions of their visual function. Clinical measures included the mean deviation (MD) from Humphrey 24-2 full threshold visual field (VF) testing, and best-corrected visual acuity (VA) measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Anchor-based (using MD and VA) and distribution-based methods were used to estimate MIDs.ResultsAnchor-based cross-sectional analyses at 66 months follow-up found a 10-letter increment in better eye VA corresponded to MIDs of 5.2 units for VAQ and 3.8 units for NEI-VFQ total scores. A 3-dB increment in the better eye MD yielded MIDs of 2.6 and 2.3 units for the same two questionnaires. In longitudinal analyses, MIDs for the VAQ were 3.2 units for a 10-letter change of VA and 3.4 units for a 3-dB change in the MD. Distribution-based MIDs were larger.ConclusionsA range of MIDs for the VAQ (2.6-6.5 units) and NEI-VFQ (2.3-3.8 units) was found. Although similar in magnitude, MIDs were sensitive to the MID estimation method, the anchor chosen, and differences between questionnaires. (ClinicalTrials.gov number, NCT00000149.).
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