Compensating patients in trials: Perspectives from an ethical committee versus sponsor.

BACKGROUND: According to European clinical research legislation, no undue influence, including financial incentives, should be used to encourage participation in clinical trials. Financial compensation should be based on the inconvenience experienced by patients and is determined by the sponsor. OBJECTIVES: The objective of this study was to assess the adequacy of patients' financial compensation by obtaining an external ethical opinion compared to the actual compensation provided. METHODS: We randomly selected and reviewed 50 clinical drug trials, including 25 academic and 25 industry-sponsored studies. An external ethics group consisting of three members from French ethics committees, blinded to the actual compensation and the sponsor, retrospectively reviewed the study characteristics and assessed whether financial compensation was appropriate. Cohen's Kappa test measured agreement between actual compensation and the ethics group's opinion, and the McNemar test measured discrepancies. RESULTS: There was no agreement between the actual financial compensation and the ethics group's opinion (K = -.07; 95% CI = [-.16-.02]). More discrepancies were found in favour of financial compensation according to the ethics group than provided by sponsors (12 vs. 2, p = .016). The ethics group recommended financial compensation in 12 out of 50 studies (24%), which were studies with a higher number of additional visits (p = .004) and were more frequently sponsored by industry (p = .008). Sponsors only provided financial compensation in 2 out of 50 studies (4%). CONCLUSION: Patients are rarely compensated despite the perceived inconvenience. Both sponsors and ethics members struggle to determine the need for financial compensation, indicating a need for more precise recommendations for both parties.

Intralesional cryosurgery to treat keloid scars: results from a retrospective study.

BACKGROUND: A variety of treatment modalities have been proposed to treat keloid scars, but outcomes are often disappointing. Intralesional cryosurgery may significantly reduce these scars. OBJECTIVE: To evaluate the clinical safety and efficacy of intralesional cryosurgery to treat keloid scars. Feedback from patients on pain, pruritus and aesthetic discomfort was recorded before and after treatment. METHODS: A total of 10 patients with 14 keloid scars resistant to conventional treatments were enrolled in a retrospective study between October 2007 and October 2013. The efficacy of this treatment was evaluated by measuring the reduction in scar surface. RESULTS: Scar surface was reduced by an average of 58.5% after intralesional cryosurgery treatment for all scars (average pre-operative keloid scar surface: 874.6 ± 954.1 mm2; average post-operative keloid scar surface: 505.8 ± 1,024.7 mm2; p = 0.002). Pain and aesthetic discomfort were significantly decreased after treatment in all patients (p = 0.008 and p = 0.012, respectively). CONCLUSION: Our data suggest that intralesional cryosurgery is an effective treatment for keloids.

Evaluation of digital medical devices: How to take into account the specificities of these solutions?

The beginning of the 21st century has seen an increasing number of digital medical devices (DMDs) arrive on the European market, bringing major benefits and changes for society. DMDs are unique in that they bring intelligence to the organisation of care, and generate and collect a wealth of real-life data with ultra-fast life cycles. They have specific requirements, particularly in terms of data security and interoperability. In France and Europe, the construction of evidence, the assessment process and evaluation methodologies with a view to purchase or reimbursement must adjust to these changes, given the specific features of these technologies. This digital leap has opened up new perspectives for healthcare, along with economic, ethical and regulatory issues. The challenge is to assess the clinical and organisational impact, reliability, safety, interoperability, efficiency and budgetary impact of DMDs in line with the requirements of new standards, guidelines and regulations. This should result in a coherent, pragmatic and proportionate evaluation, so that public decision-makers and buyers can take advantage of the potential opportunities that these digital devices offer to improve healthcare delivery. Thus, a fair and informed evaluation of DMDs would emerge, providing a solid basis to steer their inclusion into contemporary medical practices. This fundamental issue of evaluation, linked to the digital nature of these MDs, is what the round table, comprising experts from academia and/or hospitals, institutions and industry, sought to resolve. Discussions led to proposals on how DMDs should be evaluated, bearing in mind their complexity. The round table set out to identify the bottlenecks in the entire evaluation process, from the CE marking phase, compliance with French safety and interoperability requirements, through to national or local evaluation, in order to inform a purchasing policy and draw up proposals covering the entire spectrum. Ten concrete recommendations were put forward by the round table, aimed at improving the evaluation process by making it clearer and more adaptable, thus offering greater flexibility in the evaluation and decision-making stages. This well-thought-out approach is designed to facilitate a comprehensive and flexible evaluation of DMDs given the constantly evolving technological context.

Platform trials.

For the past few years, platform trials have experienced a significant increase, recently amplified by the COVID-19 pandemic. The implementation of a platform trial is particularly useful in certain pathologies, particularly when there is a significant number of drug candidates to be assessed, a rapid evolution of the standard of care or in situations of urgent need for evaluation, during which the pooling of protocols and infrastructure optimizes the number of patients to be enrolled, the costs, and the deadlines for carrying out the investigation. However, the specificity of platform trials raises methodological, ethical, and regulatory issues, which have been the subject of the round table and which are presented in this article. The round table was also an opportunity to discuss the complexity of sponsorship and data management related to the multiplicity of partners, funding, and governance of these trials, and the level of acceptability of their findings by the competent authorities.

What value do digital health solutions bring, what are the funding mechanisms and evaluations?

Digital health is currently booming, providing major innovations, particularly in terms of changing the practices of the stakeholders in the healthcare system as a whole. It allows our healthcare system to draw on new synergies between independent, hospital and medico-social professionals, as well as on high-performance digital tools for the benefit of all, users, patients and professionals. These tools, or digital solutions, have a strong potential to improve the healthcare system but also a strong potential for economic development. In this respect, the great diversity of existing and future digital solutions, as well as their vast fields of application, are prompting public and private stakeholders in the sector to question their integration into our healthcare system. The resulting challenges concern the identification of the targets they are intended for, the values they embody and, as a result, the methods of funding and evaluation. At a time when the first reimbursement terms for digital solutions are taking shape in the context of the Social Security Financing Bill for 2022, the roundtable wished to propose 8 recommendations to help structure exchanges between the various stakeholders and initiate avenues of work around the integration of digital solutions into the healthcare system. The main orientations are based on the proposal of a common and transparent reflection methodology around the technical scope of these solutions, the values they bring and the funding mechanisms. Other work will be necessary beyond the points addressed by the round table in order to go into greater depth on certain themes such as the adaptation of existing funding methods to the momentum and specificities of digital technology or the development of research work on the evaluation of the value claimed by these digital solutions.

Intravenous versus subcutaneous route pharmacokinetics of paracetamol (acetaminophen) in palliative care patients: study protocol for a randomized trial (ParaSCIVPallia).

BACKGROUND: Among palliative care (PC) patients who are administered paracetamol, the subcutaneous (SC) route is often an alternative to the intravenous (IV) route. Yet pharmacological and clinical data on whether these are equivalent pharmacokinetically are lacking. Many French palliative teams are now empirically using paracetamol by the SC route, but there are no data to support this practice. This trial aims to compare the pharmacokinetic (PK) parameters of paracetomol between the IV and SC routes in PC patients. METHODS/DESIGN: This is a randomized, open, crossover study in two PC centers. The primary endpoints are AUC0-t, AUC0-∞, Cmax, Vd, and t1/2. All adverse events will be reported for a safety analysis. Twenty adult PC patients with an IV device having spontaneous pain not related to care, with a numeric pain rate scale > 3/10, or having a systematic prescription of paracetamol as the usual treatment will be included. All patients also have to meet all eligibility criteria. CONCLUSION: This is the first study comparing PK parameters for IV paracetamol versus SC paracetamol in PC patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03944044. Registered on 4 June 2019. Committee for the protection of persons (CPP) 18.09.05.58206 approval 4 October 2018. National Drug Safety Agency (ANSM; Agence Nationale de Sécurité Médicament) MEDAECNAT-2018-09-00009 approval 29 November 2018.

Small versus Large Catheters for Ventriculostomy in the Management of Intraventricular Hemorrhage.

OBJECTIVE: Intraventricular hemorrhage (IVH) often requires the insertion of an external ventricular drain (EVD), but blood clots could occlude the catheters. Large EVD catheters may help to reduce the risk of catheter occlusion. Here, we compared small catheters with large catheters for ventriculostomy in patients suffering from IVH. METHODS: We conducted a retrospective cohort study. Patients were included if they had IVH requiring EVD insertion. We then compared baseline characteristics and outcomes of patients treated with large catheters with patients treated with small catheters. RESULTS: Between 2011 and 2015, 227 IVH patients were admitted to our 2 hospitals. Among the patients, 28 were treated in first intention with large catheters, and 46 controls were identified. Insertion of large catheter decreased the risk of temporary and permanent catheter occlusion without impact on the occurrence of intracerebral hemorrhage (ICH) related to catheter insertion. There was 38.5% more catheter-related infections in the small catheter group when compared with the large catheter group, but this result was not significant. There was no impact on functional outcomes. Surprisingly, the rate of death was higher in the large catheter group. CONCLUSIONS: In patients suffering from IVH, the use of large catheters for EVD reduced the risk of catheter occlusion without increasing the risk of ICH related to catheter insertion. The risk of catheter-related infection may subsequently be decreased by using large catheters. A prospective randomized trial would be necessary to seek out any benefits that large catheters may provide for the risk of death and functional outcome.