Improving study conduct and data quality in clinical trials of chronic pain treatments: IMMPACT recommendations

The estimated probability of progressing from phase 3 analgesic clinical trials to regulatory approval is approximately 57%, suggesting that a considerable number of treatments with phase 2 trial results deemed sufficiently successful to progress to phase 3 do not yield positive phase 3 results. Deficiencies in the quality of clinical trial conduct could account for some of this failure. An Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) meeting was convened to identify potential areas for improvement in trial conduct in order to improve assay sensitivity (i.e., ability of trials to detect a true treatment effect). We present recommendations based on presentations and discussions at the meeting, literature reviews, and iterative revisions of this article. The recommendations relate to the following areas: (1) study design (i.e., to promote feasibility), (2) site selection and staff training, (3) participant selection and training, (4) treatment adherence, (5) data collection, and (8) data and study monitoring. Implementation of these recommendations may improve the quality of clinical trial data and thus the validity and assay sensitivity of clinical trials. Future research regarding the effects of these strategies will help identify the most efficient use of resources for conducting high quality clinical trials. Perspective: Every effort should be made to optimize the quality of clinical trial data. This manuscript discusses considerations to improve conduct of pain clinical trials based on research in multiple medical fields and the expert consensus of pain researchers and stakeholders from academia, regulatory agencies, and industry

Long-term iceshelf-covered meiobenthic communities of the Antarctic continental shelf resemble those of the deep sea

Since strong regional warming has led to the disintegration of huge parts of the Larsen A and B ice shelves east of the Antarctic Peninsula in 1995 and 2002, meiofaunal communities covered by ice shelves for thousands of years could be investigated for the first time. Based on a dataset of more than 230,000 individuals, meiobenthic higher taxa diversity and composition of Larsen continental shelf stations were compared to those of deep-sea stations in the Western Weddell Sea to see whether the food-limiting conditions in the deep sea and the food-poor shelf regime at times of iceshelf coverage has resulted in similar meiobenthic communities, on the premises that food availability is the main driver of meiobenthic assemblages. We show here that this is indeed the case; in terms of meiobenthic communities, there is greater similarity between the deep sea and the inner Larsen embayments than there is similarity between the deep sea and the former Larsen B iceshelf edge and the open continental shelf. We also show that resemblance to Antarctic deep-sea meiofaunal communities was indeed significantly higher for communities of the innermost Larsen B area than for those from intermediate parts of Larsen A and B. Similarity between communities from intermediate parts and the deep sea was again higher than between those of the ice-edge and the open shelf. Meiofaunal densities were low at the inner parts of Larsen A and B, and comparable to deep-sea densities, again likely owing to the low food supply at both habitats. We suggest that meiobenthic communities have not yet recovered from the food-limiting conditions present at the time of iceshelf coverage. Meiofaunal diversity on the other hand seemed driven by sediment structure, being higher in coarser sediments