Clinical trials sponsored by industry and other private organizations

Abstract:  The present manuscript discussed some relevant aspects related to private sponsored clinical trials in dentistry. For decades, the academy has been the major responsible for research in Brazil. Distant from the trade sector, academic research has not always provided clear benefits to society. A key aspect of making benefits clearer is the process of scientific knowledge transference to decision-makers, which is, in fact, the ground of evidence-based dentistry. Although private sponsoring of clinical research seems to be part of the research progress of the business rates, investment in Brazil is lower than those observed in other countries. It is particularly important to understand that instead of creating its own rules, dentistry imported the high-quality standards originally designed for pharmaceutical studies. Therefore, it is critical to understand the original rules and how dental items are classified by regulatory agencies. In fact, knowledge about international and local regulation is a basic assumption in industry-sponsored research. Despite globalization, the identification of industry-sponsored studies through open access databases is still very hard and time-demanding. A common concern when conducting industry-sponsored trials is study biases. Fortunately, many relevant organizations, academic and industry groups, have been working seriously against that. Finally, for less experienced researchers, many aspects related to industry-sponsored studies – such as confidentiality, authorship, budget – are deeply discussed until a final version of the trial agreement can be written and signed, protecting all sides. In short, the scenario should be improved, but it already represents a nice opportunity for dental research.

 

NIH warns drug and device companies to post missing trial data 

“Hundreds of drug companies, medical device manufacturers, and universities owe the public a decade’s worth of missing data from clinical trials, federal officials warned last week.

New rules issued last week in the wake of a federal court ruling in February instructed clinical trial sponsors to submit missing data for trials conducted between 2007 and 2017 “as soon as possible.” For years, many trials conducted during that span have largely been exempted from reporting their data to ClinicalTrials.gov, a public database, meaning a decade of data about approved drugs and medical devices has never been made public.

The court’s ruling, and the federal government’s decision not to appeal it and instead to urge trial sponsors to submit the missing information, represent a major win for transparency advocates, who for years have fought to recover the decadelong gap in publicly available clinical trial data. …

The court ruling, and the resulting change in federal policy, come after years of reporting that has detailed how federal research agencies routinely fail to enforce their own rules regarding clinical trial transparency — which advocates say is critical for the public’s understanding of a given medicines’s safety and efficacy. …”

Pharmaceutical companies should publish more research open access – The BMJ

“Pharmaceutical companies fund around half of all biomedical research, but, in contrast to many public funders of research, only two companies (Takeda and Ipsen) mandate that all the research they fund must be published open access. Nevertheless, other pharmaceutical companies, including GlaxoSmithKline, are able to publish up to three quarters of the research they fund open access without a mandate. This is not bad when less than 50% of research overall is published open access….

Open Pharma has produced a position statement on open access that calls for journals to give authors who are publishing research funded by pharmaceutical companies the same rights as authors of research funded by public funders. In the 9 months since its launch, the position statement has gained over 150 endorsements, including eight publisher and 29 pharmaceutical company endorsements.

The liveliest part of the roundtable meeting was when patients called for full open access to research. Patients have not usually been included in debates about open access because they have not been considered to be “end users” of research. Nowadays, not only do patients participate at each stage of the research life cycle, from clinical trial design to establishing patient-reported outcome measurements, but they are also increasingly involved in the creation and curation of scientific studies. Yet patients can access no more than one-quarter of published clinical research. …”

Proposing minimum requirements for announcing clinical trial results during the COVID-19 pandemic | Clinical Infectious Diseases | Oxford Academic

Abstract:  Recently, results from at least three major randomized clinical trials studying management of COVID-19 have been announced via press release without accompanying information. Given the unique nature of the pandemic, results of such trials often have immediate and worldwide relevance. Yet, while press releases serve the important purpose of disseminating top-level results quickly, they are inherently limited in scope, and rarely include sufficient data to inform practice. Herein, we propose a minimum set of trial characteristics and results to be released simultaneously with clinical trial announcements. This practice will ensure data related to management of COVID-19 can be used to appropriately impact care, while responding to the needs of diverse stakeholders in the scientific and publishing communities, as well as the public at large.

 

Against pandemic research exceptionalism | Science

“The global outbreak of coronavirus disease 2019 (COVID-19) has seen a deluge of clinical studies, with hundreds registered on clinicaltrials.gov. But a palpable sense of urgency and a lingering concern that “in critical situations, large randomized controlled trials are not always feasible or ethical” (1) perpetuate the perception that, when it comes to the rigors of science, crisis situations demand exceptions to high standards for quality. Early phase studies have been launched before completion of investigations that would normally be required to warrant further development of the intervention (2), and treatment trials have used research strategies that are easy to implement but unlikely to yield unbiased effect estimates. Numerous trials investigating similar hypotheses risk duplication of effort, and droves of research papers have been rushed to preprint servers, essentially outsourcing peer review to practicing physicians and journalists. Although crises present major logistical and practical challenges, the moral mission of research remains the same: to reduce uncertainty and enable caregivers, health systems, and policy-makers to better address individual and public health. Rather than generating permission to carry out low-quality investigations, the urgency and scarcity of pandemics heighten the responsibility of key actors in the research enterprise to coordinate their activities to uphold the standards necessary to advance this mission….”

New Report – How COVID-19 is Changing Research Culture – Digital Science

“The report key findings include: 

As of 1 June 2020, there have been upwards of 42,700 scholarly articles on COVID-19 published, 3,100 clinical trials, 420 datasets, 270 patents, 750 policy documents, and 150 grants.

Preprints have rapidly established as a mainstream research output and a key part of COVID-19 research efforts. They started at relatively low levels in early January 2020 and accounted for around one quarter of research output by the beginning of May 2020.

To date, more than 8,300 organisations have been involved in supporting COVID-19 research, with over 71,800 individual researchers identified as working on COVID-19 research.

The highest intensity of research into COVID-19 began in China and gradually migrated west mirroring the movement of the virus itself.

While the US and EU have both now published more than China in journals such as The Lancet, New England Journal of Medicine and JAMA, China continues to benefit from an early mover advantage and continues to enjoy the lionshare of the citations. While research in the field is clearly moving quickly, it currently remains anchored to China’s early publications.

A density map of global COVID-19 paper production shows there are three to four major centres of research: an extended area in China composed of several cities—Wuhan, where the virus is alleged to have started, Beijing and Shanghai; Europe, specifically Italy and the UK, two of the harder hit countries; the US’s east coast research corridor including Boston and New York; and finally, a lighter focus from the Californian institutions on the West coast.

The top producing institution of COVID-19 research (since the beginning of 2020) is in China, Huazhong University of Science and Technology, followed by Harvard University and the University of Oxford.

The top healthcare producers of COVID-19 research (since the beginning of 2020) are Zhongnan Hospital of Wuhan University, then Renmin Hospital of Wuhan University, and Massachusetts General Hospital.

While the proportion of internationally co-authored work is steady, the vast majority of research on COVID to date has been unusually authored within countries.

At the time of writing, 156 grants totalling at least 20.8m USD have been awarded to COVID-themed researchers in public institutions.

Much of the clinical trial initiation activity in January and February is sponsored by China and this then begins to fall off in March, April and May. We see a similar wave for Europe and the US, but shifted back by two months, beginning in March….”

Missing clinical trial data: the knowledge gap in the safety of potential COVID-19 drugs | medRxiv

Abstract:  Abstract Objectives: Several drugs are being repurposed for the treatment of the coronavirus disease 2019 (COVID-19) pandemic based on in vitro or early clinical findings. As these drugs are being used in varied regimens and dosages, it is important to enable synthesis of existing safety data from clinical trials. However, availability of safety information is limited by a lack of timely reporting of clinical trial results on public registries or through academic publication. We aimed to analyse the knowledge gap in safety data by quantifying the number of missing clinical trial results for drugs potentially being repurposed for COVID-19. Design: ClinicalTrials.gov was searched for 19 drugs that have been identified as potential treatments for COVID-19. Relevant clinical trials for any prior indication were listed by identifier (NCT number) and checked for timely result reporting (within 395 days of the primary completion date). Additionally, PubMed and Google Scholar were searched using the NCT number to identify publications of results not listed on the registry. A second, blinded search of 10% of trials was conducted to assess reviewer concordance. Results: Of 3754 completed trials, 1516 (40.4%) did not post results on ClinicalTrials.gov or in the academic literature. 1172 (31.2%) completed trials had tabular results on ClinicalTrials.gov. A further 1066 (28.4%) completed trials had results from the literature search, but did not report results on ClinicalTrials.gov. Key drugs missing clinical trial results include hydroxychloroquine (37.0% completed trials unreported), favipiravir (77.8%) and lopinavir (40.5%). Conclusion: There is an important evidence gap for the safety of drugs being repurposed for COVID-19. This uncertainty could cause a large burden of additional morbidity and mortality during the pandemic. We recommend caution in experimental drug use for non-severe disease and urge clinical trial sponsors to report missing results retrospectively.

 

Open letter from the European Medicines Agency

“Our activities in relation to COVID-19 deserve the highest possible level of transparency and, in keeping with our commitment, the Agency will take appropriate action to share information publicly. We are currently discussing how to enhance the level of transparency for COVID-19 procedures, including the possibility of rapidly publishing clinical data for these products. The need for rapid evaluation during the current emergency will require us to depart from our usual procedures. In some cases, we will be evaluating evidence as it emerges (i.e. ‘rolling review’) and putting information in the public domain in these circumstances will be subject to additional challenges which we are currently looking to address….

Inevitably, this disruption [Brexit] required the Agency to shift all its focus to core activities that are essential for public health. Regrettably, our efforts to publish clinical data had to be put on hold in these very trying circumstances. 

In view of this and the extra effort needed to deal with COVID-19 related activities, I can’t yet commit

to reinitiate all activities related to clinical data publishing for medicines evaluated by the Agency.

However, as stated above, COVID-19 related medicines deserve special consideration because of the

overriding public interest and the need to support the international research community and foster the

collaborative effort. Further information on the concrete proposals to increase transparency of COVID19 related activities will be communicated once agreed within EMA and the EU Regulatory Network….”

Open letter from the European Medicines Agency

“Our activities in relation to COVID-19 deserve the highest possible level of transparency and, in keeping with our commitment, the Agency will take appropriate action to share information publicly. We are currently discussing how to enhance the level of transparency for COVID-19 procedures, including the possibility of rapidly publishing clinical data for these products. The need for rapid evaluation during the current emergency will require us to depart from our usual procedures. In some cases, we will be evaluating evidence as it emerges (i.e. ‘rolling review’) and putting information in the public domain in these circumstances will be subject to additional challenges which we are currently looking to address….

Inevitably, this disruption [Brexit] required the Agency to shift all its focus to core activities that are essential for public health. Regrettably, our efforts to publish clinical data had to be put on hold in these very trying circumstances. 

In view of this and the extra effort needed to deal with COVID-19 related activities, I can’t yet commit

to reinitiate all activities related to clinical data publishing for medicines evaluated by the Agency.

However, as stated above, COVID-19 related medicines deserve special consideration because of the

overriding public interest and the need to support the international research community and foster the

collaborative effort. Further information on the concrete proposals to increase transparency of COVID19 related activities will be communicated once agreed within EMA and the EU Regulatory Network….”

The Global Research Data Alliance community response to the global COVID-19 pandemic | RDA

“Data drives rapid response and informed decision making during public health emergencies. There is a need for timely and accurate collection, reporting and sharing of data with the research community, public health practitioners, clinicians and policy makers. Accurate and rapid availability of data will inform assessment of the severity, spread and impact of a pandemic to implement efficient and effective response strategies.

The Research Data Alliance (RDA) is a volunteer community of over 10,500 professionals from 145 countries across the globe. In less than two months, the community responded to an urgent call for action and defined much needed, comprehensive recommendations and guidelines for data sharing under the present COVID-19 circumstances. 
Today, 28 May 2020, we publish the pre-final version of the RDA COVID-19 Recommendations and Guidelines covering four research areas – clinical data, omics practices, epidemiology and social sciences. This document is also complimented by overarching areas focusing on legal and ethical considerations, research software, community participation and indigenous data.
The detailed guidelines in this body of work aim to help stakeholders follow best practices to maximise the efficiency of their work and act as a blueprint for the current and future health emergencies. The recommendations aim to help policymakers and funders maximise timely, quality data sharing and appropriate responses to health emergencies, particularly COVID-19. 

The report specifically emphasises the importance of the following during the COVID-19 emergency response:  …”