Is the genie out of the bottle? Digital platforms and the future of clinical trials

This is the final version. Available on open access from Taylor & Francis via the DOI in this recordIs it possible to conduct impartial clinical trials in a world full of digital networking tools that patients can use to coordinate themselves and act against research protocols? This paper builds on an ethnography of PatientsLikeMe, a company running an Internet social media network where patients with different conditions share their clinical data with standardised questionnaires. The company faced a serious dilemma in 2011 when some ALS patients, members of the site, started sharing data about a phase II clinical trial of an experimental drug (NP001) in which some of them were participating, to anticipate the experiment’s outcomes and understand each one’s allocation over trial arms. In parallel, some other patients were using the site and other web tools to coordinate and run their own replication of the trial with homebrew mixes of industrial grade chemicals. PatientsLikeMe researchers reflected on their position as networks managers and eventually decided to use the collected data to develop their own analysis of the efficacy of the original compound, and of the homebrewers’ compound. They presented the NP001 events as a case in point for articulating a new social contract for clinical research. This paper analyses these events, first, by understanding the clinical trial as an experiment organisation form that can succeed only as long as its protocol can be enforced; second, we observe how web networks make it dramatically easier for the trial protocol to be violated; finally, we point out how a potentially dangerous confluence of interests over web networks could incubate developments that disrupt the status quo without creating a robust and safe alternative for experimentation. We conclude by warning about the interests of the pharmaceutical industry in exploiting patients’ methodological requests to its own advantage.European Research CouncilEngineering and Physical Sciences Research Council (EPSRC

Patients’ online interventions can scupper clinical trials

This is the author accepted manuscriptAlan Turing Institut

Facts, Norms and Expected Utility Functions

International audienceIn this paper we want to explore an argumentative pattern that provides a normative justification for expected utility functions grounded on empirical evidence, showing how it worked in three different episodes of their development. The argument claims that we should prudentially maximize our expected utility since this is the criterion effectively applied by those who are considered wisest in making risky choices (be it gamblers or businessmen). Yet, to justify the adoption of this rule, it should be proven that this is empirically true: i.e., that a given function allows us to predict the choices of that particular class of agents. We show how expected utility functions were introduced and contested in accordance to this pattern in the 18th century and how it recurred in the 1950s when M. Allais made his case against the neobernoullians

CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.

BACKGROUND: Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load. METHODS AND FINDINGS: Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger), we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI) of: 0.35 (0.30-0.40) for counts <200 cells/µl, 0.81 (0.71-0.92) for counts 200 to <350 cells/µl, 0.74 (0.66-0.83) for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99) for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl. CONCLUSIONS: Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl

Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies

BACKGROUND: Health care for people living with HIV has improved substantially in the past two decades. Robust estimates of how these improvements have affected prognosis and life expectancy are of utmost importance to patients, clinicians, and health-care planners. We examined changes in 3 year survival and life expectancy of patients starting combination antiretroviral therapy (ART) between 1996 and 2013. METHODS: We analysed data from 18 European and North American HIV-1 cohorts. Patients (aged ≥16 years) were eligible for this analysis if they had started ART with three or more drugs between 1996 and 2010 and had at least 3 years of potential follow-up. We estimated adjusted (for age, sex, AIDS, risk group, CD4 cell count, and HIV-1 RNA at start of ART) all-cause and cause-specific mortality hazard ratios (HRs) for the first year after ART initiation and the second and third years after ART initiation in four calendar periods (1996–99, 2000–03 [comparator], 2004–07, 2008–10). We estimated life expectancy by calendar period of initiation of ART. FINDINGS: 88 504 patients were included in our analyses, of whom 2106 died during the first year of ART and 2302 died during the second or third year of ART. Patients starting ART in 2008–10 had lower all-cause mortality in the first year after ART initiation than did patients starting ART in 2000–03 (adjusted HR 0·71, 95% CI 0·61–0·83). All-cause mortality in the second and third years after initiation of ART was also lower in patients who started ART in 2008–10 than in those who started in 2000–03 (0·57, 0·49–0·67); this decrease was not fully explained by viral load and CD4 cell count at 1 year. Rates of non-AIDS deaths were lower in patients who started ART in 2008–10 (vs 2000–03) in the first year (0·48, 0·34–0·67) and second and third years (0·29, 0·21–0·40) after initiation of ART. Between 1996 and 2010, life expectancy in 20-year-old patients starting ART increased by about 9 years in women and 10 years in men. INTERPRETATION: Even in the late ART era, survival during the first 3 years of ART continues to improve, which probably reflects transition to less toxic antiretroviral drugs, improved adherence, prophylactic measures, and management of comorbidity. Prognostic models and life expectancy estimates should be updated to account for these improvements

Dynamics and distribution of bacterial and archaeal communities in oil-contaminated temperate coastal mudflat mesocosms

Mudflats are ecologically important habitats that are susceptible to oil pollution, but intervention is difficult in these fine-grained sediments, and so clean-up usually relies on natural attenuation. Therefore, we investigated the impact of crude oil on the bacterial, diatom and archaeal communities within the upper parts of the diatom-dominated sediment and the biofilm that detached from the surface at high tide. Biodegradation of petroleum hydrocarbons was rapid, with a 50 % decrease in concentration in the 0–2-mm section of sediment by 3 days, indicating the presence of a primed hydrocarbon-degrading community. The biggest oil-induced change was in the biofilm that detached from the sediment, with increased relative abundance of several types of diatom and of the obligately hydrocarbonoclastic Oleibacter sp., which constituted 5 % of the pyrosequences in the oiled floating biofilm on day 3 compared to 0.6 % in the non-oiled biofilm. Differences in bacterial community composition between oiled and non-oiled samples from the 0–2-mm section of sediment were only significant at days 12 to 28, and the 2–4-mm-sediment bacterial communities were not significantly affected by oil. However, specific members of the Chromatiales were detected (1 % of sequences in the 2–4-mm section) only in the oiled sediment, supporting other work that implicates them in anaerobic hydrocarbon degradation. Unlike the Bacteria, the archaeal communities were not significantly affected by oil. In fact, changes in community composition over time, perhaps caused by decreased nutrient concentration and changes in grazing pressure, overshadowed the effect of oil for both Bacteria and Archaea. Many obligate hydrocarbonoclastic and generalist oil-degrading bacteria were isolated, and there was little correspondence between the isolates and the main taxa detected by pyrosequencing of sediment-extracted DNA, except for Alcanivorax, Thalassolituus, Cycloclasticus and Roseobacter spp., which were detected by both methods

Shells and humans: molluscs and other coastal resources from the earliest human occupations at the Mesolithic shell midden of El Mazo (Asturias, Northern Spain)

Human populations exploited coastal areas with intensity during the Mesolithic in Atlantic Europe, resulting in the accumulation of large shell middens. Northern Spain is one of the most prolific regions, and especially the so-called Asturian area. Large accumulations of shellfish led some scholars to propose the existence of intensification in the exploitation of coastal resources in the region during the Mesolithic. In this paper, shell remains (molluscs, crustaceans and echinoderms) from stratigraphic units 114 and 115 (dated to the early Mesolithic c. 9 kys cal BP) at El Mazo cave (Asturias, northern Spain) were studied in order to establish resource exploitation patterns and environmental conditions. Species representation showed that limpets, top shells and sea urchins were preferentially exploited. One-millimetre mesh screens were crucial in establishing an accurate minimum number of individuals for sea urchins and to determine their importance in exploitation patterns. Environmental conditions deduced from shell assemblages indicated that temperate conditions prevailed at the time of the occupation and the morphology of the coastline was similar to today (rocky exposed shores). Information recovered relating to species representation, collection areas and shell biometry reflected some evidence of intensification (reduced shell size, collection in lower areas of exposed shores, no size selection in some units and species) in the exploitation of coastal resources through time. However, the results suggested the existence of changes in collection strategies and resource management, and periods of intense shell collection may have alternated with times of shell stock recovery throughout the Mesolithic.This research was performed as part of the project “The human response to the global climatic change in a littoral zone: the case of the transition to the Holocene in the Cantabrian coast (10,000–5000 cal BC) (HAR2010-22115-C02-01)” funded by the Spanish Ministry of Economy and Competitiveness. AGE was funded by the University of Cantabria through a predoctoral grant and IGZ was funded by the Spanish Ministry of Economy and Competitiveness through a Juan de la Cierva grant. We also would like to thank the University of Cantabria and the IIIPC for providing support, David Cuenca-Solana, Alejandro García Moreno and Lucia Agudo Pérez for their help. We also thank Jennifer Jones for correcting the English. Comments from two anonymous reviewers helped to improve the paper