Pilot studies for phase III trials - which are comparative randomized trials designed to provide preliminary evidence on the clinical efficacy of a drug or intervention - are routinely performed in many clinical areas. Also commonly know as "feasibility" or "vanguard" studies, they are designed to assess the safety of treatment or interventions; to assess recruitment potential; to assess the feasibility of international collaboration or coordination for multicentre trials; to increase clinical experience with the study medication or intervention for the phase III trials. They are the best way to assess feasibility of a large, expensive full-scale study, and in fact are an almost essential pre-requisite. Conducting a pilot prior to the main study can enhance the likelihood of success of the main study and potentially help to avoid doomed main studies. The objective of this paper is to provide a detailed examination of the key aspects of pilot studies for phase III trials including: 1) the general reasons for conducting a pilot study; 2) the relationships between pilot studies, proof-of-concept studies, and adaptive designs; 3) the challenges of and misconceptions about pilot studies; 4) the criteria for evaluating the success of a pilot study; 5) frequently asked questions about pilot studies; 7) some ethical aspects related to pilot studies; and 8) some suggestions on how to report the results of pilot investigations using the CONSORT format.

Treatment of dementia with cholinesterase inhibitors and memantine can result in statistically significant but clinically marginal improvement in measures of cognition and global assessment of dementia.

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Background:The clinical significance of elevated cardiac troponin (cTn) level in patients in the intensive care unit (ICU) is uncertain. We reviewed the frequency of cTn elevation and its association with mortality and length of ICU stay in these patients.Methods: Studies were identified using MEDLINE, EMBASE, and reference list review. We included observational studies of critically ill patients that measured cTn at least once and reported the frequency of elevated cTn or outcome (mortality and length of ICU or hospital stay). We pooled the odds ratios (ORs) using the inverse variance method in studies that conducted multivariable analysis to examine the relationship between elevated cTn and mortality (adjusted analysis). We calculated the weighted mean difference in length of stay between patients with and without elevated cTn and pooled the results using the inverse variance method (unadjusted analysis).Results: A total of 23 studies involving 4492 critically ill patients were included. In 20 studies, elevated cTn was found in a median of 43% (interquartile range, 21% to 59%) of 3278 patients. In adjusted analysis (6 studies comprising 1706 patients), elevated cTn was associated with an increased risk of death (OR, 2.5; 95% confidence interval [CI], 1.9 to 3.4; PϽ.001). In the unadjusted analysis (8 studies comprising 1019 patients), elevated cTn was associated with an increased length of ICU stay of 3.0 days (95% CI, 1.0 to 5.1 days; P=.004) and an increased length of hospital stay of 2.2 days (95% CI, −0.6 to 4.9; P=.12).Conclusions: Elevated cTn measurements among critically ill patients are associated with increased mortality and ICU length of stay. Research is needed to clarify the underlying causes of elevated cTn in this population and to examine their clinical significance.

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Background and Objectives: Chronic obstructive pulmonary disease (COPD) affects over 250 million people globally, carrying a notable economic burden. This systematic literature review aimed to highlight the economic burden associated with moderate-to-very severe COPD and to investigate key drivers of healthcare resource utilization (HRU), direct costs and indirect costs for this patient population. Materials and Methods: Relevant publications published between January 1, 2006 and November 14, 2016 were captured from the Embase, MEDLINE and MEDLINE In-Process databases. Supplemental searches from relevant 2015-2016 conferences were also performed. Titles and abstracts were reviewed by two independent researchers against predefined inclusion and exclusion criteria. Studies were grouped by the type of economic outcome presented (HRU or costs). Where possible, data were also grouped according to COPD severity and/or patient exacerbation history. Results: In total, 73 primary publications were included in this review: 66 reported HRU, 22 reported direct costs and one reported indirect costs. Most of the studies (94%) reported on data from either Europe or North America. Trends were noted across multiple studies for higher direct costs (including mean costs per patient per year and mean costs per exacerbation) being associated with increasingly severe COPD and/or a history of more frequent or severe exacerbations. Similar trends were noted according to COPD severity and/or exacerbation history for rate of hospitalization and primary care visits. Multivariate analyses were reported by 29 studies and demonstrated the statistical significance of these associations. Several other drivers of increased costs and HRU were highlighted for patients with moderate-to-very severe COPD, including comorbidities, and treatment history. Conclusion: Moderate-to-very severe COPD represents a considerable economic burden for healthcare providers despite the availability of efficacious treatments and comprehensive guidelines on their use. Further research is warranted to ensure cost-efficient COPD management, to improve treatments and ease budgetary pressures.

A new form of model for COPD was conceptualized, implemented, and internally validated, based on a series of linked equations using epidemiological data (ECLIPSE) and cost data (TORCH). This Galaxy model predicts COPD outcomes from treatment effects on disease attributes such as lung function, exacerbations, symptoms, or exercise capacity; further external validation is required.

BackgroundAsthma, one of the most common chronic respiratory diseases, affects about 3 million Canadians. The objective of this study is to provide a comprehensive evaluation of the published literature that reports on the clinical, economic, and humanistic burden of asthma in Canada.MethodsA search of the PubMed, EMBASE, and EMCare databases was conducted to identify original research published between 2000 and 2011 on the burden of asthma in Canada. Controlled vocabulary with “asthma” as the main search concept was used. Searches were limited to articles written in English, involving human subjects and restricted to Canada. Articles were selected for inclusion based on predefined criteria like appropriate study design, disease state, and outcome measures. Key data elements, including year and type of research, number of study subjects, characteristics of study population, outcomes evaluated, results, and overall conclusions of the study, were abstracted and tabulated.ResultsThirty-three of the 570 articles identified by the clinical and economic burden literature searches and 14 of the 309 articles identified by the humanistic burden literature searches met the requirements for inclusion in this review. The included studies highlighted the significant clinical burden of asthma and show high rates of healthcare resource utilization among asthma patients (hospitalizations, ED, physician visits, and prescription medication use). The economic burden is also high, with direct costs ranging from an average annual cost of $366 to $647 per patient and a total annual population-level cost ranging from ~ $46 million in British Columbia to ~ $141 million in Ontario. Indirect costs due to time loss from work, productivity loss, and functional impairment increase the overall burden. Although there is limited research on the humanistic burden of asthma, studies show a high (31%-50%) prevalence of psychological distress and diminished QoL among asthma patients relative to subjects without asthma.ConclusionsAs new therapies for asthma become available, economic evaluations and assessment of clinical and humanistic burden will become increasingly important. This report provides a comprehensive resource for health technology assessment that will assist decision making on asthma treatment selection and management guidelines in Canada.