Putting participants and study partners FIRST when clinical trials end early.

Between 2018 and 2019, multiple clinical trials ended earlier than planned, resulting in calls to improve communication with and support for participants and their study partners ("dyads"). The multidisciplinary Participant Follow-Up Improvement in Research Studies and Trials (Participant FIRST) Work Group met throughout 2021. Its goals were to identify best practices for communicating with and supporting dyads affected by early trial stoppage. The Participant FIRST Work Group identified 17 key recommendations spanning the pre-trial, mid-trial, and post-trial periods. These focus on prospectively allocating sufficient resources for orderly closeout; developing dyad-centered communication plans; helping dyads build and maintain support networks; and, if a trial stops, informing dyads rapidly. Participants and study partners invest time, effort, and hope in their research participation. The research community should take intentional steps toward better communicating with and supporting participants when clinical trials end early. The Participant FIRST recommendations are a practical guide for embarking on that journey.

Placebo-controlled trial of amantadine for severe traumatic brain injury.

BACKGROUND: Amantadine hydrochloride is one of the most commonly prescribed medications for patients with prolonged disorders of consciousness after traumatic brain injury. Preliminary studies have suggested that amantadine may promote functional recovery. METHODS: We enrolled 184 patients who were in a vegetative or minimally conscious state 4 to 16 weeks after traumatic brain injury and who were receiving inpatient rehabilitation. Patients were randomly assigned to receive amantadine or placebo for 4 weeks and were followed for 2 weeks after the treatment was discontinued. The rate of functional recovery on the Disability Rating Scale (DRS; range, 0 to 29, with higher scores indicating greater disability) was compared over the 4 weeks of treatment (primary outcome) and during the 2-week washout period with the use of mixed-effects regression models. RESULTS: During the 4-week treatment period, recovery was significantly faster in the amantadine group than in the placebo group, as measured by the DRS score (difference in slope, 0.24 points per week; P=0.007), indicating a benefit with respect to the primary outcome measure. In a prespecified subgroup analysis, the treatment effect was similar for patients in a vegetative state and those in a minimally conscious state. The rate of improvement in the amantadine group slowed during the 2 weeks after treatment (weeks 5 and 6) and was significantly slower than the rate in the placebo group (difference in slope, 0.30 points per week; P=0.02). The overall improvement in DRS scores between baseline and week 6 (2 weeks after treatment was discontinued) was similar in the two groups. There were no significant differences in the incidence of serious adverse events. CONCLUSIONS: Amantadine accelerated the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness. (Funded by the National Institute on Disability and Rehabilitation Research; ClinicalTrials.gov number, NCT00970944.).

Review of food policy and consumer issues of mercury in fish.

Public health messages regarding seafood consumption are confounded by long standing dietary advice promoting the healthfulness of consuming fish and recent warnings concerning dangerous mercury levels in specified fish. The warnings vary by federal agency and are directed to vulnerable subpopulations, notably women of childbearing age, pregnant women, nursing mothers and young children. The issue of mercury in fish has received considerable media coverage, attention from consumer organizations and public policy review. The net result is an area of seemingly contradictory advice directed to consumers and health professionals on the type and quantity of fish safe to consume. This message that fish is nutritious and healthy is particularly understood by educated and affluent subpopulations who can afford a variety of fish in their diet. This review addresses the contradictory rhetoric and reviews the state and federal agency policy positions. It considers the arguments for and against disclosing mercury-related information and its anticipated impact on the extended health benefits of fish consumption versus the risk to vulnerable subpopulations. The issue of balancing and targeting healthy messages and dietary warnings on fish is important because within the U.S. childbearing population, it is conservatively estimated that 250,000 women may be exposing their fetuses to higher levels of methylmercury than is in federal public health guidelines; two million more may not be consuming enough low-mercury fish.

Consumer perceptions of graded, graphic and text label presentations for qualified health claims.

On December 18, 2002, the Food and Drug Administration (FDA) announced the Consumer Health Information for Better Nutrition Initiative. The initiative's goal is to make available more and better information about conventional foods and dietary supplements to help Americans improve their health and reduce risk of disease by making sound dietary decisions. It included a rating system to assess the "weight of the publicly available evidence." It assigns one of four ranked levels to the claim thus resulting in qualified health claims. Two phases of research were conducted by the International Food Information Council (IFIC) Foundation. Qualitative research to assess consumer understanding, vocabulary, and familiarity with claims helped with the design and orientation of the second quantitative research phase. The quantitative phase employed a Web-based survey. The claim formats included: report card graphic, report card text, embedded claim text, point-counterpoint, structure/function claim, and nutrient content claim. Respondents were asked to rate the product for perceived strength of scientific evidence provided to support the claim, and questions about the product's perceived healthfulness, quality, safety, and purchase intent. Consumers found it difficult to discriminate across four levels and showed inclination to project the scientific validity grade onto other product attributes. Consumers showed preference for simpler messages.

Predictors of outcome in prolonged posttraumatic disorders of consciousness and assessment of medication effects: A multicenter study.

OBJECTIVES: To develop predictive models of recovery from the vegetative state (VS) and minimally conscious state (MCS) after traumatic brain injury (TBI) and to gather preliminary evidence on the impact of various psychotropic medications on the recovery process to support future randomized controlled trials. Design Longitudinal observational cohort design, in which demographic information, injury and acute care history, neuroimaging data, and an initial Disability Rating Scale (DRS) score were collected at the time of study enrollment. Weekly follow-up data, consisting of DRS score, current psychoactive medications, and medical complications, were gathered until discharge from inpatient rehabilitation. SETTING: Seven acute inpatient rehabilitation facilities in the United States and Europe with specialized programs for treating patients in the VS and MCS. PARTICIPANTS: People with TBI (N=124) who were in the VS or MCS 4 to 16 weeks after injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: DRS score at 16 weeks after injury and time until commands were first followed (among those participants demonstrating no command following at study enrollment). Results DRS score at enrollment, time between injury and enrollment, and rate of DRS change during the first 2 weeks of poststudy observation were all highly predictive of both outcomes. No variables related to injury characteristics or lesions on neuroimaging were significant predictors. Of the psychoactive medications, amantadine hydrochloride was associated with greater recovery and dantrolene sodium was associated with less recovery, in terms of the DRS score at 16 weeks but not the time until commands were followed. More detailed analysis of the timing of functional improvement, with respect to the initiation of amantadine provided suggestive, but not definitive, evidence of the drug's causal role. CONCLUSIONS: These findings show the feasibility of improving outcome prediction from the VS and MCS using readily available clinical variables and provide suggestive evidence for the effects of amantadine and dantrolene, but these results require confirmation through randomized controlled trials.