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

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

This is the final version. Available from Routledge via the DOI in this record. Is 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.Alan Turing InstituteEuropean Research Counci

The trade-off between impartiality and freedom in the 21st Century Cures Act

This is the final version. Available from the University of Pittsburgh via the DOI in this record. Randomized controlled trials test new drugs using various debiasing devices to prevent participants from manipulating the trials. But participants often dislike controls, arguing that they impose a paternalist constraint on their legitimate preferences. The 21st Century Cures Act, passed by US Congress in 2016, encourages the Food and Drug Administration to use alternative testing methods, incorporating participants’ preferences, for regulatory purposes. We discuss, from a historical perspective, the trade-off between trial impartiality and participants’ freedom. We argue that the only way out is considering which methods improve upon the performance of conventional trials in keeping dangerous or inefficacious compounds out of pharmaceutical marketsMinisterio de Ciencia e Innovació

Short Communication: Laboratory assessment of ammonia volatilization from pig slurries applied on intact soil cores from till and no-till plots

Aim of study: Agricultural activities are the main source of volatilized ammonia (NH3). Maximum rates are reached within a few hours after slurry application. This study aimed to evaluate the influence of soil texture, tillage and slurry dry matter (DM) on NH3 volatilization.Area of study: Mediterranean semiarid environments (NE Spain).Material and methods: Ammonia volatilization from pig slurry directly applied on the soil surface was quantified in the laboratory, in soil samples from two experimental sites with different soil textures: silty loam and sandy loam. Field treatments consisted of two tillage management practices: till by disc-harrowing or no-till. At topdressing (cereal tillering), tillage treatments were combined with slurries of different DM contents applied onto the silty loam soil. Measurements were done for two cereal cropping seasons and during the period of maximum NH3 flux (12 h after slurry application). A photoacoustic analyzer was used.Main results: Slurry spreading at sowing resulted in low volatilization (0.7-9% of NH4+-N applied) as it also did at topdressing (0.3-1.4% of NH4+-N applied). At sowing, ammonia volatilization from high DM slurry (>7.5%) was significantly enhanced by no-till in both soils. At topdressing, this result was also found in records on silty loam soil. No differences were found between tillage systems when slurry of low DM content was applied, whatever the soil texture and application moment. Although NH3 volatilization was probably affected by the laboratory conditions, the comparisons between treatments were still valuable.Research highlights: Ammonia volatilization abatement can be improved (<1 kg NH3-N ha-1) if fertilization is done after crop establishment using low DM slurries (<3.5%).info:eu-repo/semantics/publishedVersio

Corrigendum to "Biogeography of planktonic bacterial communities across the whole Mediterranean Sea" published in Ocean Sci., 9, 585–595, 2013

No abstract available

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