Pilot and feasibility studies: extending the conceptual framework

In 2016, we published a conceptual framework outlining the conclusions of our work in defining pilot and feasibility studies. Since then, the CONSORT extension to randomised pilot and feasibility trials has been published and there have been further developments in the pilot study landscape. In this paper, we revisit and extend our framework to incorporate the various feasibility pathways open to researchers, which include internal pilot studies. We consider, with examples, when different approaches to feasibility and pilot studies are more effective and efficient, taking into account the pragmatic decisions that may need to be made. The ethical issues involved in pilot studies are discussed. We end with a consideration of the funders’ perspective in making difficult resource decisions to include feasibility work and the policy implications of these; throughout, we provide examples of the uncertainties and compromises that researchers have to navigate to make progress in the most efficient way

Progression from external pilot to definitive randomised controlled trial : a methodological review of progression criteria reporting

Objectives: Prespecified progression criteria can inform the decision to progress from an external randomised pilot trial to a definitive randomised controlled trial. We assessed the characteristics of progression criteria reported in external randomised pilot trial protocols and results publications, including whether progression criteria were specified a priori and mentioned in prepublication peer reviewer reports. Study design: Methodological review. Methods: We searched four journals through PubMed: British Medical Journal Open, Pilot and Feasibility Studies, Trials and Public Library of Science One. Eligible publications reported external randomised pilot trial protocols or results, were published between January 2018 and December 2019 and reported progression criteria. We double data extracted 25% of the included publications. Here we report the progression criteria characteristics. Results: We included 160 publications (123 protocols and 37 completed trials). Recruitment and retention were the most frequent indicators contributing to progression criteria. Progression criteria were mostly reported as distinct thresholds (eg, achieving a specific target; 133/160, 83%). Less than a third of the planned and completed pilot trials that included qualitative research reported how these findings would contribute towards progression criteria (34/108, 31%). The publications seldom stated who established the progression criteria (12/160, 7.5%) or provided rationale or justification for progression criteria (44/160, 28%). Most completed pilot trials reported the intention to proceed to a definitive trial (30/37, 81%), but less than half strictly met all of their progression criteria (17/37, 46%). Prepublication peer reviewer reports were available for 153/160 publications (96%). Peer reviewer reports for 86/153 (56%) publications mentioned progression criteria, with peer reviewers of 35 publications commenting that progression criteria appeared not to be specified. Conclusions: Many external randomised pilot trial publications did not adequately report or propose prespecified progression criteria to inform whether to proceed to a future definitive randomised controlled trial

Transparency of informed consent in pilot and feasibility studies is inadequate: a single-center quality assurance study

Background Pilot and feasibility studies (PAFS) often have complex objectives aimed at assessing feasibility of conducting a larger study. These may not be clear to participants in pilot studies. Methods Here, we aimed to assess the transparency of informed consent in PAFS by investigating whether researchers communicate, through patient information leaflets and consent forms, key features of the studies. We collected this data from original versions of these documents submitted for ethics approval and the final approved documents for PAFS submitted to the Hamilton Integrated Research Ethics Board, Canada. Results One hundred eighty-four PAFS, submitted for ethics approval from 2004 to 2020, were included, and we found that of the approved consent documents which were provided to participants, 83.2% (153) stated the terms “pilot” or “feasibility” in their title, 12% (22) stated the definition of a pilot/feasibility study, 42.4% (78) of the studies stated their intent to assess feasibility, 19.6% (36) stated the specific feasibility objectives, 1.6% (3) stated the criteria for success of the pilot study, and 0.5% (1) stated all five of these criteria. After ethics review, a small increase in transparency occurred, ranging from 1.6 to 2.8% depending on the criteria. By extracting data from the protocols of the PAFS, we found that 73.9% (136) stated intent to assess feasibility, 71.2% (131) stated specific feasibility objectives, and 33.7% (62) stated criteria for success of the study to lead to a larger study. Conclusion The transparency of informed consent in PAFS is inadequate and needs to be specifically addressed by research ethics guidelines. Research ethics boards and researchers ought to be made aware and mindful of best practices of informed consent in the context of PAFS

A new calibrated sunspot group series since 1749: statistics of active day fractions

Although the sunspot-number series have existed since the mid-19th century, they are still the subject of intense debate, with the largest uncertainty being related to the "calibration" of the visual acuity of individual observers in the past. Daisy-chain regression methods are applied to inter-calibrate the observers which may lead to significant bias and error accumulation. Here we present a novel method to calibrate the visual acuity of the key observers to the reference data set of Royal Greenwich Observatory sunspot groups for the period 1900-1976, using the statistics of the active-day fraction. For each observer we independently evaluate their observational thresholds [S_S] defined such that the observer is assumed to miss all of the groups with an area smaller than S_S and report all the groups larger than S_S. Next, using a Monte-Carlo method we construct, from the reference data set, a correction matrix for each observer. The correction matrices are significantly non-linear and cannot be approximated by a linear regression or proportionality. We emphasize that corrections based on a linear proportionality between annually averaged data lead to serious biases and distortions of the data. The correction matrices are applied to the original sunspot group records for each day, and finally the composite corrected series is produced for the period since 1748. The corrected series displays secular minima around 1800 (Dalton minimum) and 1900 (Gleissberg minimum), as well as the Modern grand maximum of activity in the second half of the 20th century. The uniqueness of the grand maximum is confirmed for the last 250 years. It is shown that the adoption of a linear relationship between the data of Wolf and Wolfer results in grossly inflated group numbers in the 18th and 19th centuries in some reconstructions

The effects of cyanobacteria and the cyanobacterial toxin microcystin-LR on Ca2+ transport and Na+/K+-atpase in tilapia gills

Contains fulltext : 29004.pdf (publisher's version ) (Open Access

Geohydrologic study of the West Lake Basin

The purpose of this investigation was to (1) collect and interpret geochemical data on the surface, unconfined, and confined waters of the West Lake Basin, and (2) evaluate the potential for radiochemical contamination of the uppermost confined aquifers. The report assesses the suitability of Gable Mountain Pond for receiving waste water from 200 East Area operations and applies a predictive digital computer model to assess the impacts to the groundwater regime of maintaining, increasing, or decreasing water discharge into Gable Mountain Pond. East of the 200 East Area lies a natural depression which has been dammed and used as a liquid waste disposal site (B Pond). B Pond waste waters directly recharge the underlying unconfined aquifer. This report will examine the suitability of using B Pond for receiving additional waste waters which would otherwise be discharged to Gable Mountain Pond. A predictive digital computer model will be used for assessments involving various discharges into B Pond

Summary of INEL research on the iron-enriched basalt waste form

This report summarizes the knowledge base on the iron-enriched basalt (IEB) waste form developed at the Idaho National Engineering Laboratory (INEL) during 1979--1982. The results presented discuss the applicability of IEB in converting retrieved transuranic (TRU) waste from INEL's Radioactive Waste Management Complex (RWMC) into a vitreous/ceramic (glassy/rock) stable waste form suitable for permanent disposal in an appropriate repository, such as the Waste Isolation Pilot Plant (WIPP) in New Mexico. Borosilicate glass (BSG), the approved high-level waste form, appears unsuited for this application. Melting the average waste-soil mix from the RWMC produces the IEB composition and attempting to convert IEB to the BSG composition would require additions of substantial B{sub 2}0{sub 3}, Na, and SiO{sub 2} (glass frit). IEB requires processing temperatures of 1400 to 1600{degrees}C, depending upon the waste composition. Production of the IEB waste form, using Joule heated melters, has proved difficult in the past because of electrode and refractory corrosion problems associated with the high temperature melts. Higher temperature electric melters (arc and plasma) are available to produce this final waste form. Past research focused on extensive slag property measurements, waste form leachability tests, mechanical, composition, and microstructure evaluations, as well as a host of experiments to improve production of the waste form. Past INEL studies indicated that the IEB glass-ceramic is a material that will accommodate and stabilize a wide range of heterogeneous waste materials, including long lived radionuclides and scrap metals, while maintaining a superior level of chemical and physical performance characteristics. Controlled cooling of the molten IEB and subsequent heat treatment will produce a glass-ceramic waste form with superior leach resistance