Phase II clinical trials with time‐to‐event endpoints: optimal two‐stage designs with one‐sample log‐rank test

Phase II clinical trials are often conducted to determine whether a new treatment is sufficiently promising to warrant a major controlled clinical evaluation against a standard therapy. We consider single‐arm phase II clinical trials with right censored survival time responses where the ordinary one‐sample logrank test is commonly used for testing the treatment efficacy. For planning such clinical trials, this paper presents two‐stage designs that are optimal in the sense that the expected sample size is minimized if the new regimen has low efficacy subject to constraints of the type I and type II errors. Two‐stage designs, which minimize the maximal sample size, are also determined. Optimal and minimax designs for a range of design parameters are tabulated along with examples. Copyright © 2013 John Wiley & Sons, Ltd.     

Two‐stage designs for cross‐over bioequivalence trials

The topic of applying two‐stage designs in the field of bioequivalence studies has recently gained attention in the literature and in regulatory guidelines. While there exists some methodological research on the application of group sequential designs in bioequivalence studies, implementation of adaptive approaches has focused up to now on superiority and non‐inferiority trials. Especially, no comparison of the features and performance characteristics of these designs has been performed, and therefore, the question of which design to employ in this setting remains open. In this paper, we discuss and compare ‘classical’ group sequential designs and three types of adaptive designs that offer the option of mid‐course sample size recalculation. A comprehensive simulation study demonstrates that group sequential designs can be identified, which show power characteristics that are similar to those of the adaptive designs but require a lower average sample size. The methods are illustrated with a real bioequivalence study example. Copyright © 2015 John Wiley & Sons, Ltd.     

Research capacity strengthening: donor approaches to improving and assessing its impact in low‐ and middle‐income countries

Increasing attention, and a concomitant increase in funds, is being devoted to the strengthening of research capacity for health within low‐ and middle‐income countries. Yet approaches to research capacity strengthening (RCS) are still new, and there is much debate about how to strengthen something that is so difficult to define, let alone measure. This paper aims to inform our understanding of how research capacity is being strengthened, and how we might consider the effectiveness of these initiatives. It does this by examining (a) understandings of and approaches to RCS, and (b) different ways in which RCS is monitored and evaluated. The study included a literature review, internet search, and analysis of the web pages and available documents for six donor organizations key to health RCS. E‐mail and telephone discussions were conducted with experts in the area of health RCS, as well as semi‐structured telephone interviews with representatives from the six identified organizations. The study found that understandings of and approaches to RCS are wide ranging. We are at the early stages of knowing how best to identify, target and affect the many factors that are important for stronger research capacity. Furthermore, as RCS initiatives become more wide‐ranging and complex, they become more difficult to monitor and evaluate. Donors are struggling with many challenges associated with tracking RCS initiatives. There is no consensus on the best methods or tools to use. There is a clear need for improved strategies and the development of a tried and tested framework for RCS tracking. Copyright © 2010 John Wiley & Sons, Ltd.     

Patients as qualitative data analysts: Developing a method for a process evaluation of the ‘Improving the Safety and Continuity of Medicines management at care Transitions’ (ISCOMAT) cluster randomised control trial

BackgroundHow to meaningfully partner with patients as data analysts remains obscure. A process evaluation of the ‘Improving the Safety and Continuity Of Medicines management at care Transitions’ (ISCOMAT) cluster randomised control trial of an intervention for improving medicines use for people living with heart failure is being conducted. The intervention includes patient held information on heart medicines and care, enhanced communication between hospital and community pharmacists, and increased engagement of community pharmacists with patient care post‐hospital discharge. ISCOMAT patients living with heart failure were interviewed about experiences with the intervention. We sought to gain insights from patients on data collected to enhance our understanding of experiences with the intervention.ObjectiveTo develop a method for involving patients as analysts of qualitative data in a process evaluation.DesignPatients and researchers co‐analysed qualitative data. A framework method was applied involving; familiarisation, coding, developing an analytical framework and interpretation. The process was facilitated through home working and a workshop with a training component.ResultsThe co‐designed framework enabled researchers to map all further patient interview data. Patients'' specialist knowledge enhanced understanding of how the ISCOMAT intervention can be best implemented.ConclusionsPatients’ unique experiences can enhance validity and rigour in data analysis through sharing their interpretations of qualitative data. The involvement process is crucial in elucidating knowledge and avoiding tokenism. As analysts, patients gain an appreciation of research processes, building trust between researchers and patients. Group dynamics and involving patients throughout the whole research process are important considerations.     

Full‐Time,Part‐Time Full‐Time,and Part‐Time Fathers: Father Identities Following Divorce

This grounded theory study examined how 20 newly divorced, nonresidential fathers manage their fatherhood identities. The theory created from this study proposes that fathers' perceptions of (a) father‐child relationships, (b) how their children's fiscal needs are met, and (c) barriers to their physical interactions with their children influence their fatherhood identities. In spite of all fathers identifying themselves as involved, three types of fathers emerged: full‐time fathers, part‐time full‐time fathers, and part‐time fathers. The findings suggest that men's conceptualizations of father involvement are influenced by their postdivorce experiences with nonresidential fatherhood.     

Was it good for you too? Impediments to conducting university‐based collaborative research with communities experiencing disadvantage

Objective: Collaborative and participatory research (CPR) models are increasingly recognised as methodologically, ethically and practically appropriate to conducting health and welfare research involving disadvantaged communities. This paper identifies impediments to CPR and proposes measures to support and encourage future CPR in Australian universities.
Methods: This paper draws on a small qualitative study of university-based CPR projects in Melbourne. The study involved a literature review and interviews with 23 participants, comprising university-based researchers and community liaison officers, and community representatives involved in university-based research projects.
Results: The paper outlines four main difficulties encountered by university-based researchers and community liaison staff in conducting CPR. These are: managing community sensitivities, the time-consuming nature of the work and diverse tasks involved, difficulty securing adequate research funding, and a concern that CPR was detrimental to academic careers.
Conclusion: CPR in universities might be supported in the future through providing CPR training for researchers, employing additional community liaison staff, recognising community reports within the Australian research quality evaluation system Excellence in Research for Australia, adopting supportive policies within universities and provision of dedicated CPR funding.
Implications: In the current Australian university context of competitive funding, further research into CPR nationally, alongside dedicated resources and policies are required to maximise the benefits of this approach.     

Point estimation and p‐values in phase II adaptive two‐stage designs with a binary endpoint

Clinical trials in phase II of drug development are frequently conducted as single‐arm two‐stage studies with a binary endpoint. Recently, adaptive designs have been proposed for this setting that enable a midcourse modification of the sample size. While these designs are elaborated with respect to hypothesis testing by assuring control of the type I error rate, the topic of point estimation has up to now not been addressed. For adaptive designs with a prespecified sample size recalculation rule, we propose a new point estimator that both assures compatibility of estimation and test decision and minimizes average mean squared error. This estimator can be interpreted as a constrained posterior mean estimate based on the non‐informative Jeffreys prior. A comparative investigation of the operating characteristics demonstrates the favorable properties of the proposed approach. Copyright © 2016 John Wiley & Sons, Ltd.     

The Early Effects of Medicare's Mandatory Hospital Pay‐for‐Performance Program

Objective

To evaluate the impact of hospital value-based purchasing (HVBP) on clinical quality and patient experience during its initial implementation period (July 2011–March 2012).

Data Sources

Hospital-level clinical quality and patient experience data from Hospital Compare from up to 5 years before and three quarters after HVBP was initiated.

Study Design

Acute care hospitals were exposed to HVBP by mandate while critical access hospitals and hospitals located in Maryland were not exposed. We performed a difference-in-differences analysis, comparing performance on 12 incentivized clinical process and 8 incentivized patient experience measures between hospitals exposed to the program and a matched comparison group of nonexposed hospitals. We also evaluated whether hospitals that were ultimately exposed to HVBP may have anticipated the program by improving quality in advance of its introduction.

Principal Findings

Difference-in-differences estimates indicated that hospitals that were exposed to HVBP did not show greater improvement for either the clinical process or patient experience measures during the program''s first implementation period. Estimates from our preferred specification showed that HVBP was associated with a 0.51 percentage point reduction in composite quality for the clinical process measures (p > .10, 95 percent CI: −1.37, 0.34) and a 0.30 percentage point reduction in composite quality for the patient experience measures (p > .10, 95 percent CI: −0.79, 0.19). We found some evidence that hospitals improved performance on clinical process measures prior to the start of HVBP, but no evidence of this phenomenon for the patient experience measures.

Conclusions

The timing of the financial incentives in HVBP was not associated with improved quality of care. It is unclear whether improvement for the clinical process measures prior to the start of HVBP was driven by the expectation of the program or was the result of other factors.