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Decentralized clinical trials involving the use of digital tools to facilitate remote research are gaining momentum. Rapid advancements in digital technologies have supported the adoption of these trials. These innovations facilitate virtual interactions between clinical trial teams and participants by making it easier to collect, transfer and store electronic data. While some studies have demonstrated the potential for these approaches to reduce barriers to clinical trial participation, they are associated with several challenges that may create or worsen existing health inequalities and limit the generalizability of trial results. Here we review the potential for digitally enabled and decentralized clinical trials to enhance clinical trial participation in an equitable manner. We describe the key barriers individuals from underserved groups may face, and provide recommendations to promote equity, diversity and inclusion.

Patient-reported outcomes (PROs) are increasingly used in healthcare research to provide evidence of the benefits and risks of interventions from the patient perspective and to inform regulatory decisions and health policy. The use of PROs in clinical practice can facilitate symptom monitoring, tailor care to individual needs, aid clinical decision-making and inform value-based healthcare initiatives. Despite their benefits, there are concerns that the potential burden on respondents may reduce their willingness to complete PROs, with potential impact on the completeness and quality of the data for decision-making. We therefore conducted an initial literature review to generate a list of candidate recommendations aimed at reducing respondent burden. This was followed by a two-stage Delphi survey by an international multi-stakeholder group. A consensus meeting was held to finalize the recommendations. The final consensus statement includes 19 recommendations to address PRO respondent burden in healthcare research and clinical practice. If implemented, these recommendations may reduce PRO respondent burden.

Background Seasonal interpandemic influenza causes >200,000 annual hospitalizations in the United States. Optimal antiviral treatment in hospitalized patients is not established.Methods During three interpandemic influenza seasons, 137 patients hospitalized with suspected acute influenza were randomized to 5-day treatment with intravenous peramivir 400 mg or 200 mg once daily or oral oseltamivir 75 mg twice daily. Time to clinical stability and quantitative changes in viral titres from nasopharyngeal specimens were primary and key secondary end points, respectively.Results Infection was confirmed in 122 patients with influenza A (H1N1), influenza A (H3N2) or influenza B. Median times (95% CI) to clinical stability were 37.0 h (22.0, 48.7) with peramivir 400 mg, 23.7 h (16.0, 38.9) with peramivir 200 mg and 28.1 h (22.0, 37.0) with oseltamivir (P=0.306). Patients (n=97) who were clinically unstable at enrolment had median times (95% CI) to clinical stability of 24.3 h (21.2, 47.5) with peramivir 400 mg, 31.0 h (17.2, 47.7) with peramivir 200 mg and 35.5 h (23.3, 37.9) with oseltamivir (P=0.541). Titres of influenza A viruses in nasopharyngeal specimens decreased similarly across treatments, but more rapid decreases in titres of influenza B occurred with peramivir treatment. There were no deaths among patients with confirmed influenza and the incidence of adverse events was low and generally similar among treatment groups.Conclusions Treatment of acute seasonal influenza in hospitalized adults with either peramivir or oseltamivir resulted in generally similar clinical outcomes. Treatment with peramivir was generally safe and well tolerated and could be of benefit in this population.

Microtubules are involved in a wide variety of cellular functions1–3and are major components of many subcellular structures (for example, the centriole, mitotic spindle, cytoskeleton and flagellar apparatus). The ability of microtubules to serve in such a diversity of functions may be accounted for, at least in part, by heterogeneity in the constituent types of α- and β-tubulin subunits4–10in different microtubules. Higher eukaryotes generally possess several tubulin genes and this may account for part of the heterogeneity of tubulin subunits11–13. However, the unicellular eukaryote, Chlamydomonas reinhardii, has only two α- and two β- tubulin genes14–16, which suggests that some of the variation in tubulin subunits seen in this organism5,8may arise as a result of post-translational modification. This notion is supported by the experiments of Lefebvre et al.8who compared flagellar tubulins with those produced by in vitro translation of tubulin mRNAs. Here we show that a form of α-tubulin subunit apparently confined to the Chlamydomonas cell body is converted, post-translationally, into a flagellar form of α-tubulin and that this modification is dependent on flagellar assembly. We discuss possible mechanisms for these modifications and their implications for the generation of unique types of microtubules having specialized functions within the cell.

REMOVAL of the flagella from the biflagellate alga Chlamydomonas reinhardi results in the rapid production of new flagella1–3. Flagellar regeneration is 80–85% complete within 60 min (Fig. 1). Indirect evidence obtained from in vitro translation of polyribosomes and mRNA from deflagellated gametes1has indicated that flagellar regeneration is accompanied by a strong but transient induction of tubulin synthesis. Kinetic analysis showed that tubulin mRNA could be detected in polyribosomes in as little as 15 min after deflagellation. Since the cytoplasm contains a reserve of tubulin of sufficient size to supply at least one-third to one-half of the tubulin subunits required for flagellar reassembly1,3, the rapid initiation of tubulin synthesis following deflagellation suggested the existence of a highly sensitive system for detecting and responding to the cell's anticipated need for additional tubulin. As an approach to seeking such a mechanism, we have carried out studies to determine if the depletion of tubulin reserves during flagellar outgrowth might provide the signal for the induction of tubulin synthesis. We present here two types of experimental evidence which clearly demonstrate that the induction of tubulin synthesis is independent of the utilisation of tubulin reserves during flagellar regeneration.