Principal Features of Industry-Funded Trials that Posted Informed Consent Forms on ClinicalTrials.gov: a Cross-Sectional Analysis.

We aim to characterize industry-funded trials that have posted the informed consent forms (ICFs), and to assess whether the role played by industry as 'sponsor' or 'collaborator' could impact several relevant variables. A cross-sectional study was conducted on ClinicalTrials.gov on all industry-funded trials registered on or before 25 February 2023. We registered types of intervention, current recruitment status, design, enrollment, and countries involved. For trials with special interest to potential participants and investigators and/or clinicians an analysis of the role played by industry as 'sponsor' or 'collaborator' was performed. Of 116,281 industry-funded trials registered, 741 (0.6%) had posted ICFs. Most of these trials were categorized as 'completed' (n = 408) or 'terminated' (n = 107). The review of a sample of 359 trials showed that most were on drugs and/or biologics (59%), were randomized (51%), conducted exclusively in the USA (72%), and had posted results (79%), protocols (92%), and statistical analysis plans (SAPs) (89%). Trials in which industry participated as 'collaborator' were significantly more likely to post ICFs when trials were in the 'active, not recruiting' phase (OR 4.70, 99.71% CI 1.59-13.9, p < 0.001) than industry-sponsored trials. This was also the case when assessing drugs/biologics (OR 2.64, 99.71% CI 1.25-5.58, p < 0.001). Conversely, companies acting as 'sponsors' were significantly more likely to post ICFs with trials assessing devices, radiation interventions and/or diagnostic tests (OR 0.37, 99.71% CI 0.17-0.79, p < 0.001) than when participating as 'collaborators'. While industry-funded trials rarely post ICFs, when they do, they are highly compliant with transparency requirements. Regulations and ethics codes should consider requiring posting of protocols, SAPs, and ICFs for all clinical trials, regardless the type of sponsor.

[Participant-funded clinical trials on rare diseases]. / Ensayos clínicos en enfermedades raras financiados por los participantes.

The development of medicines for certain rare diseases can be frustrated by lack of funding. In certain cases the patients themselves, or their relatives, occasionally fund the clinical trial in which they will be treated with the investigational medicine. There are 3models of self-funded research: 2of them, "pay to try" and "pay to participate", have already been put into practice. The third, the "plutocratic" proposal, which has been recently put forward is still a theoretical model. In this work the scientific, social and ethical benefits and risks of the 2clinical research models, "pay to participate" and the "plutocratic" proposal, are reviewed. Patient-funded clinical trials are frequently performed through crowdfunding. The most controversial aspects of this funding modality are also addressed in this article from several perspectives. Finally, a future scenario that would allow the launching of self-funded clinical trials in Spain by the "plutocratic" proposal is proposed.

Articles provided insufficient information to conduct an appropriate retrospective assessment of the pragmatic/explanatory features of medicine trials with the PRECIS-2 tool.

PURPOSE: To assess whether, in the retrospective assessment of the pragmatic/explanatory features of pragmatic randomized controlled trials (pRCTs), the nine PRECIS-2 domain scores using the information provided in articles were modified after using the information reported in other publicly available sources. METHODS: This is a cross-sectional study of participant-level pRCTs published in July 2018 to December 2019 in the four highest-impact general medicine journals. The articles described the main results of pRCTs assessing medicines in one or more arms that were not in the pre-licensing phases. The information reported in trial full protocols, published protocols, and other publications, registries, and trial websites were assessed and scored, and compared with that previously obtained after reviewing the information reported in the articles. RESULTS: Out of 76 articles on pRCTs, 13 (17%) were included in the analysis. All were two-arm trials, assessing medicines only (n = 7), medicine vs device (n = 2), medicine vs surgery (n = 1), or medicine vs placebo (n = 3). Seven were open-label trials, and six had any type of masking. All except one had the full protocol available and/or published protocol; seven had other types of publication available. The assessment of the nine PRECIS-2 domains with the information reported in the 13 articles was changed in all trials after using the information included in other additional available sources. Between one (n = 1 article) and six (n = 2) domains were modified in each pRCT. The domains that most commonly changed were "organization" (n = 12), "recruitment" (n = 11), and "follow-up" (n = 8). "Primary outcome" and "primary analysis" were not modified in any trial. Eight percent of all domains could not be assessed due to inadequate or lack of information in seven articles; those were "recruitment" (n = 3), "organization" (n = 3), "setting" (n = 2), and "flexibility:adherence" (n = 1). CONCLUSION: Articles describing the trial main results are usually insufficient for the appropriate retrospective assessment of the pragmatic/explanatory features of a pRCT by authors not involved in the conduct of the trial. To address this issue, editors should require the submission of the original full protocol and final full protocol with the history of amendments to be published as supplementary material to the article.

Participant-funded clinical trials on rare diseases.

The development of medicines for certain rare diseases can be cut short by lack of funding. In certain cases the patients themselves, or their relatives, occasionally fund the clinical trial in which they will be treated with the investigational medicine. There are three models of self-funded clinical research: two of them, 'pay to try' and 'pay to participate', have already been put into practice. The third, the 'plutocratic' proposal, which has been recently put forward is still a theoretical model. In this work the scientific, social and ethical benefits and risks of the two clinical research models, 'pay to participate and the 'plutocratic' proposal, are reviewed. Patient-funded clinical trials are frequently performed through crowdfunding. The most controversial aspects of this funding modality are also addressed in this article from several perspectives. Finally, a future scenario that would allow the launching of self-funded clinical trials in Spain by the 'plutocratic' proposal is proposed.

The potential exploitation of research participants in high income countries who lack access to health care.

There are millions of individuals living in North America and the European Union who lack access to healthcare services. When these individuals participate in research, they are at increased risk of being exposed to the risks and burdens of clinical trials without realizing the benefits that result from them. The mechanisms that have been proposed to ensure that research participants in low- and middle-income countries are not exploited are unlikely to protect participants in high-income countries. The present manuscript argues that one way to address concerns about exploitation in high-income countries would be to require sponsors to provide targeted benefits such as medical treatment during the trial, or the study drug after the trial. The latter could be achieved through extension studies, expanded access programs, or named-patient programs. Sponsors also might provide non-medical benefits, such as education or social support. Ethical and regulatory guidance should be revised to ensure that research participants in high-income countries who lack access to healthcare services receive sufficient benefits.

[Registration of observational studies: it is time to comply with the Declaration of Helsinki requirement]. / El registro de los estudios observacionales: es el momento de cumplir el requerimiento de la Declaración de Helsinki.

Publication bias is a serious deficiency in the current system of disseminating the results of human research studies. Clinical investigators know that, from an ethical standpoint, they should prospectively register clinical trials in a public registry before starting them. In addition, it is believed that this approach will help to reduce publication bias. However, most studies conducted in humans are observational rather than experimental. It is estimated that less than 2% out of 2 million concluded or ongoing observational studies have been registered. The 2013 revision of the Declaration of Helsinki requires registration of any type of research study involving humans or identifiable samples or data. It is proposed that funding agencies, such as the Fondo de Investigaciones Sanitarias, as well as private companies, require preregistration of observational studies before providing funding. It is also proposed that Research Ethics Committees which, following Spanish regulation, have been using the Declaration as the framework for assessing the ethics of clinical trials with medicines since 1990, should follow the same provisions for the assessment of health-related observational studies: therefore, they should require prospective registration of studies before granting their final approval. This would allow observational study investigators to be educated in complying with an ethical requirement recently introduced in the most important ethical code for research involving humans.