Contemporary clinical trials
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Contemp Clin Trials · Jan 2011
Toxicity equivalence range design (TEQR): a practical Phase I design.
This paper introduces the target equivalence range (TEQR) design, a frequentist implementation of the modified toxicity probability interval (mTPI) design, as a competitor to the standard 3+3 design (3+3). The 3+3 is the work horse design in Phase I. It is good at determining if a safe dose exits, but provides poor accuracy and precision in estimating the level of toxicity at the maximum tolerated dose (MTD). Its main competitor, the continual reassessment method (CRM) has not found a true niche in the Phase I armamentarium resulting from statistical and implementation complexities. ⋯ The TEQR offers trial designers a competitor to the 3+3 for ease of implementation with better operating characteristics and the added attraction of a glimpse of activity at the MTD. The R package TEQR, freely available from the comprehensive R archive network, includes functions to calculate dose escalation guidelines and operating characteristics.
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Contemp Clin Trials · Jan 2011
Randomized Controlled TrialResearch to Encourage Exercise for Fibromyalgia (REEF): use of motivational interviewing design and method.
Fibromyalgia (FM), defined as the presence of both chronic widespread pain and the finding of 11/18 tender points on examination, is an illness associated with major personal and societal burden. Supervised aerobic exercise is an important treatment modality to improve patient symptoms. Unfortunately, adherence to an exercise regimen after a structured supervised program is disappointingly low. ⋯ Details on the study design, MI program, and treatment fidelity are provided in the paper. Outcome assessments at week 12, week 24 and week 36 will test the immediate, intermediate and long-term effects of exercise-based MI on adherence (as measured by the Community Health Activities Model Program for Seniors/CHAMPS and accelerometer) and clinical outcomes. When completed, REEF will determine whether exercise-based MI could be utilized as a management strategy to sustain the clinical benefits of exercise for FM.
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Contemp Clin Trials · Jan 2011
Statistical methods for a phase II oncology trial with a growth modulation index (GMI) endpoint.
For cytostatic cancer therapies, alternatives to traditional phase II endpoints are needed. Von Hoff (1998) proposed an intrapatient progression-free survival (PFS) ratio, the growth modulation index (GMI). Current practice in estimation of the GMI success rate is conservative and omits a measure of uncertainty. ⋯ Using a proof of concept criterion of {P(GMI≥1)≥θ}, a simulation investigation found that a θ of 50%, for sample sizes between 20 and 30 patients, had type I error of ≤20% and a power to detect Von Hoff's 1.33 effect of ≥80%. When the amount of censoring was ≥20%, the midrank estimator had a minimum of 14% greater power over the simple percentage estimator for the GMI success rate. Future investigations reporting the GMI should consider adopting the midrank methodology.
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Contemp Clin Trials · Sep 2010
Comparative StudySingle momentary assessments are not reliable outcomes for clinical trials.
Patient reported outcomes (PROs) play an essential role in clinical trials, though questions have been raised about the accuracy of PROs using long recall periods. This paper examines the utility of a PRO employing a single momentary assessment of pain in a sample of community rheumatology patients. We explore the accuracy and reliability of a single assessment versus the average of multiple assessments taken over 1-week, which is considered a common outcome reporting period. ⋯ Longitudinal analysis of change scores across 3 months also demonstrated considerable unreliability of single-point measures, thus the statistical power generated by single-point assessments was considerably less than the more reliable week average. Our conclusion is that single momentary assessments, at least for representing an outcome over a period of a week, are not ideal measures. We discuss alternative measurement strategies for efficiently collecting PRO data for a 1-week period using end-of-day diaries or 7-day recall measures.
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A Contract Research Organization (CRO) is a service organization that provides support to the pharmaceutical industry and offers a wide range of "outsourced" pharmaceutical research services to aid in R&D process and is thus an essential tool for undertaking clinical trials in the present scenario when high stakes are involved in the drug discovery process. This industry also offers a safe option of investment as the industry is largely recession-proof, with a significant upscale growth. Presently India occupies a very small pie of the global market share in the Clinical Trials Industry but it is estimated to conduct nearly 5% of global clinical trials by 2012. ⋯ According to a recent study by Mckinsey & Company, the Indian Clinical Research Industry can attract $1.5 bn of revenue from US and EU by 2010. Such an increase in outsourcing from the western countries has led the global pharma companies and Indian entrepreneurs to set up Contract Research Organizations (CROs) in India. To bring this into realization and fulfil the market demand, while simultaneously aiding in improving the country's economical standards and market position, joint and well-coordinated efforts on part of the government, industry, and working professionals are needed in terms of regulatory affairs, audits, transparency in work affairs, garnering patient confidence, and pharmacovigilance.