Clinical Trial Transparency Research Articles

Streamlining Clinical Trial Data from Raw to Regulatory Submission with R Shiny and Pharmaverse

In recent years, the pharmaceutical and biotech industries have increasingly adopted open-source tools to enhance the efficiency, transparency, and reproducibility of clinical trial data analysis. R Shiny, a web application framework for R, has become a key component in creating interactive dashboards and visualizations that support real-time data exploration and decision-making. As part of the Pharmaverse ecosystem, R Shiny plays a vital role in regulatory submissions, data analysis, and reporting, offering dynamic, user-friendly interfaces for clinical trial monitoring, patient safety reporting, and efficacy analysis. This abstract explores the application of R Shiny within the Pharmaverse, emphasizing its seamless integration with tools such as Tplyr and admiral for generating CDISC-compliant SDTM and ADaM datasets. Metadata management and validation are facilitated through OAK, ensuring consistency and traceability. The automated creation of Define.xml using tools like defineR further enhances transparency and regulatory compliance. Through case studies and practical examples, this abstract highlights how R Shiny and related tools improve data transparency, accelerate decision-making, and support regulatory compliance in clinical trials. By leveraging these open-source technologies, clinical trial teams can streamline data workflows, enhance collaboration, and improve outcomes, ultimately driving innovation within the pharmaceutical industry. The integration of these tools into a cohesive framework significantly enhances the submission process to regulatory bodies like the FDA and EMA, ensuring that clinical data meets both industry and regulatory standards.

Clinical trial transparency and disclosure from the medical writing perspective

It’s been more than 6 years since our last Medical Writing edition dedicated to clinical trial transparency and disclosure. Since then, we have seen the full implementation of the long-awaited EU Clinical Trials Regulation (CTR), the pause and restart of EMA Policy 0070, and of course a global pandemic which resulted in a world-wide surge in freedom of information requests for Covid-19 vaccine clinical trial data. Although many of the regulations and policies governing public disclosure of clinical trial data and documents remain unchanged, we have seen significant changes in the way these are implemented. As those of us who work in this field know all too well, the landscape is ever changing, and it is essential to keep up to date with those changes. Resources such as the Drug Information Association Clinical Trial Disclosure Community, PHUSE Data Transparency Working Group, and Clarity and Openness in Reporting-E3 based (CORE) Reference provide invaluable updates and insights. This issue of Medical Writing touches on a number of different aspects of clinical trial transparency and disclosure, all of which involve medical writers as key stakeholders

Navigating the new era of clinical trial transparency

This issue of Medical Writing comes at a time when the summer holidays are behind us. Here’s hoping it has been a relaxing and rejuvenating time for all. As we get back to our day-to-day work, our fellow EMWA colleagues bring us an expert insight into the latest requirements in clinical trial transparency and disclosure. As medical writers, this has been on our agenda for many years now, but as we look to the future, transparency in clinical research is emerging as more than just a regulatory requirement – it is a cornerstone of public trust and ethical responsibility.

Advancing Diversity and Transparency in Hematologic Clinical Trials

Advancing Diversity and Transparency in Hematologic Clinical Trials

Is full transparency in clinical trials an achievable goal?

Is full transparency in clinical trials an achievable goal?

Barriers and best practices to improving clinical trials transparency at UK public research institutions: A qualitative interview study

ObjectivesSince 2017, the UK government has made concerted efforts to ensure the dissemination of clinical trials conducted at public research institutions. This study aims to understand how stakeholders within these institutions responded to these pressures and modified internal policies and processes while identifying best practices and barriers to improved transparency practice. MethodsResearch governance and trial management staff from UK public research institutions (i.e., Universities and NHS Trusts) in England, Scotland and Wales participated in semi-structured interviews. Interviews were analysed using thematic analysis, aided by the framework method. ResultsBetween November 2020 and July 2021, 14 individual participants were recruited from 11 different institutions. They worked in research governance, administration, and management. Almost universally, new policies and procedures have been established to ensure investigators are aware of, and supported in, fulfilling their transparency commitments, however challenges remain. Trials of medicinal products, as the most closely regulated research, consequently received the most attention. National professional networks aid in sharing knowledge and best practice within this community. ConclusionsInvestment in the institutional governance of transparency is essential to achieving optimal transparency practices. Universities and hospitals share responsibility for ensuring research is performed and reported to regulatory standards. Facing political pressure, public research institutions in the UK have made efforts to improve their transparency practice which can provide key insights for similar efforts elsewhere.

Overcoming confidential information challenges faced by study sponsors today

As health authorities aim to increase clinical trial transparency and visibility to the public, pharmaceutical manufacturers are facing new pressure points. New regulations require the disclosure of clinical trial application data, many of which contain sensitive and confidential information about company intellectual property including, but not limited to, its manufacturing methods, drug composition, names of suppliers, and future development plans. Many manufacturers are examining their processes to minimise references to this confidential data during the document authoring process and how they track and identify confidential information throughout the study lifecycle. This has created a catalyst for medical writing, transparency, legal, and regulatory teams to collaborate and enhance their processes to minimise disruption to the trial approval process while embracing the opportunities to share more with the public.

Towards transparency: adoption of WHO best practices in clinical trial registration and reporting among top medical research funders in the USA

ObjectiveTo assess to what extent the clinical trial policies of the largest public and philanthropic funders of clinical research in the United States meet WHO best practices in trial registration...

Disparities in Clinical Trial Enrollment and Reporting in Rectal Cancer: A Systematic Review and Demographic Comparison to the National Cancer Database.

Cancer care guidelines based on clinical trial data in homogenous populations may not be applicable to all rectal cancer patients. The aim of this study was to evaluate whether patients enrolled in rectal cancer clinical trials (CTs) are representative of United States (U.S.) rectal cancer patients. Prospective rectal cancer CTs from 2010 to 2019 in the United States were systematically reviewed. In trials with multiple arms reporting separate demographic variables, each arm was considered a separate CT group in the analysis. Demographic variables considered in the analysis were age, sex, race/ethnicity, facility location throughout the United States, rural vs urban geography, and facility type. Participant demographics from trial and the National Cancer Database (NCDB) participants were compared using chi-squared goodness of fit and one-sample t-test where applicable. Of 50 CT groups identified, 42 (82%) studies reported mean or median age. Trial participants were younger compared to NCDB patients (P < .001 all studies). All but three trials had fewer female patients than NCDB (48.2% female, P < .001). Less than half the CT groups reported on race or ethnicity. Eighteen out of 22 trials (82%) had a smaller percentage of Black patients and 4 out of 8 (50%) trials had fewer Hispanic or Spanish origin patients than the NCDB. No CTs reported comorbidities, socioeconomic factors, or education. CT primary sites were largely at academic centers and in urban areas. The present study supports the need for improved demographic representation and transparency in rectal cancer clinical trials.

Posting of clinical trial results and other critical information from completed medicines trials on ClinicalTrials.gov.

Clinical trials transparency requires trial registration and the posting of results on a public register. US regulations also require the posting of protocols and statistical analysis plans (SAPs). For US Federal agency funded trials to be started on or after 21January2019, informed consent forms (ICFs) must also be posted. Posting these documents is not mandatory in other countries. We aimed to assess compliance with US regulations of trials conducted in the US or in other countries with respect to ICFs, protocols, SAPs, and results. This cross-sectional analysis (27April2023) comprised completed medicines trials to be started on or after 21January2019 registered on ClinicalTrials.gov. Trial data were registered by funder type (i.e., 'US federal agencies', industry, and 'all others') and development phase. Of 5,584 trials, 40% were conducted solely in the US. 47% and 12% of US and non-US trials had posted results. Some 40% of US trials had posted protocols and SAPs as did 9% of trials conducted in other countries. Only 10% (US) and 2% (other countries) of trials had posted ICFs. When the margin of the last 2 and 12 months after primary completion date were considered in the analysis, ICF posting rate did not change, but posting results increased to 64% for US trials. 'US Federal agencies' funded trials were significantly more likely to post ICFs than industry [OR 23.9 (12.5-45.7; <.001)] or 'all others' [OR 3.16 (1.79-5.56; <.001)]. Future interventions should be considered to encourage timely posting of trial results and information.

Data transparency and demographic representation in approval packages of FDA-approved oncology drugs from 2012-2021.

1594 Background: Over the past decade, the U.S. Food and Drug Administration (FDA) has leveraged regulations and guidance documents to accelerate improvements in demographic reporting and encourage adequate representation of minorities in clinical trials. This cross-sectional study aims to assess the impact of these interventions by characterizing demographic data reporting and representation by sex, age, and racial and ethnic identity in pivotal trials supporting novel cancer therapeutics approved by the FDA from 2012 through 2021. Methods: Study demographic data were abstracted from FDA drug approval packages and US cancer population demographic data was abstracted from US Cancer Statistics. The percentages of trials reporting sex, age, racial and ethnic identity of participants in drug approval packages were calculated and participation to prevalence ratios (PPRs) were calculated by dividing the percentage of participants in each demographic by the percentage of the US cancer population in each group. PPRs were constructed for each pivotal trial by cancer type. Adequate representation was defined as PPR 0.8-1.2 and the proportion of trials which were adequately representative of each demographic was calculated and trended over time. Results: From 2012 through 2021, the FDA approved 118 cancer therapeutics, based on 131 pivotal trials. For drugs approved 2012-2016, the majority of associated pivotal trials reported participation based on sex (100% of trials), age (100%) and White (98%), Black (75%) or Asian (84%) racial identity, but not American Indian or Alaskan Native racial identity (18%) or Hispanic ethnic identity (41%). For drugs approved 2017-2021, there were no significant improvements in demographic data reporting, although there was a trend towards increased reporting on Hispanic ethnic identity from 2012-2016 (41%) to 2017-2021 (65%) (p= 0.06). For drugs approved 2012-2016, most pivotal trials adequately represented female participants (78% of trials) and participants identifying as White (87%), but few pivotal trials adequately represented older adults (7%), participants identifying as Black (11%), American Indian or Alaskan Native (0%), Asian (18%) or Hispanic (5%). Representation in pivotal trials did not significantly improve for any demographic for drugs approved 2017-2021 (p&gt;0.05). Conclusions: This study found that the last decade’s efforts to improve demographic data transparency and representation in clinical trials have not yet borne fruit for novel cancer therapeutics. More consequential FDA regulations may be necessary. Beyond the FDA, demographic data transparency and adequate minority representation in oncology clinical trials is an all-stakeholder responsibility. A more just clinical trial infrastructure requires greater collaboration between the FDA, sponsors, enrollers, contract research organizations and cooperative groups.

Clinical Trial Data Transparency in the EU: Is the New Clinical Trials Regulation a Game-Changer?

The benefits of access to clinical trial data are related to their inestimable value from the perspective of clinical trial participants, society as a whole, public health systems and scientific progress. In light of the development of innovative data analysis technologies, access to raw clinical trial data opens up an ever-widening array of possibilities: it can profoundly facilitate machine data analysis for, inter alia, hypothesis generation, risk modelling, counterfactual simulation and – finally – drug repurposing and development. The enactment of the new Clinical Trials Regulation (EU) No. 536/2014 (CTR) and introduction of the Clinical Trials Information System (CTIS) were heralded as ensuring a level of transparency in clinical trials that is sufficient to contribute to protecting public health and fostering the innovation capacity of European medical research, while recognizing the legitimate economic interests of sponsors. This paper presents the hitherto binding rules for the disclosure of clinical trial data and, against this background, their new framework, introduced by the CTR. In addition to assessing whether the CTR’s objectives are fulfilled, this paper examines whether the latest changes impact the hitherto existing rules on protection of regulatory data via regulatory exclusivities. Finally, it points out concerns regarding whether data gathered in the CTIS can be efficiently used by innovative data analysis technologies for further processing for both commercial and non-commercial purposes.

Definition and rationale for placebo composition: Cross-sectional analysis of randomized trials and protocols published in high-impact medical journals.

Inadequate description of trial interventions in publications has been repeatedly reported, a problem that extends to the description of placebo controls. Without describing placebo contents, it cannot be assumed that a placebo is inert. Pharmacologically active placebos complicate accurate estimation and interpretation of efficacy and safety data. In this study, we sought to assess whether placebo contents are described in study protocols and publications of trials published in high-impact medical journals. We identified all placebo-controlled randomized clinical trials (RCTs) published in 2016 in Annals of Internal Medicine, The BMJ, the Journal of the American Medical Association (JAMA), The Lancet, and the New England Journal of Medicine (NEJM). We included all trials with publicly available study protocols. From journal publications and associated study protocols, we searched and recorded: description of placebo contents; the amount of each placebo ingredient; and investigators' stated rationale for selection of placebo ingredients. We included 113 placebo-controlled RCTs. Of the 113 trials, placebo content was described in 22 (19.5%) journal publications and 51 (45.1%) study protocols. The amount of each placebo ingredient was described in 15 (13.3%) journal publications and 47 (41.6%) study protocols. None of the journal publications explained the rationale for the choice of placebo ingredients, whereas a rationale was provided in 4 (3.5%) study protocols. The stated rationales were to ensure the placebo was visually indistinguishable from the experimental intervention (N = 3) and ensure comparability with a previous study (N = 1). There is no accessible record of the composition of placebos for approximately half of high-impact RCTs, even with access to study protocols. This impedes reproducibility and raises unanswerable questions about what effects-beneficial or harmful-the placebo may have had on trial participants, potentially confounding an accurate assessment of the experimental intervention's safety and efficacy. Considering that study protocols are unabridged, detailed documents describing the trial design and methodology, the fact that less than half of the study protocols described the placebo contents raises concerns about clinical trial transparency. To improve the reproducibility and potential of placebo-controlled RCTs to provide reliable evidence on the efficacy and safety profile of drugs and other experimental interventions, more detail regarding placebo contents must be included in trial documents.

Institutional dashboards on clinical trial transparency for University Medical Centers: A case study.

University Medical Centers (UMCs) must do their part for clinical trial transparency by fostering practices such as prospective registration, timely results reporting, and open access. However, research institutions are often unaware of their performance on these practices. Baseline assessments of these practices would highlight where there is room for change and empower UMCs to support improvement. We performed a status quo analysis of established clinical trial registration and reporting practices at German UMCs and developed a dashboard to communicate these baseline assessments with UMC leadership and the wider research community. We developed and applied a semiautomated approach to assess adherence to established transparency practices in a cohort of interventional trials and associated results publications. Trials were registered in ClinicalTrials.gov or the German Clinical Trials Register (DRKS), led by a German UMC, and reported as complete between 2009 and 2017. To assess adherence to transparency practices, we identified results publications associated to trials and applied automated methods at the level of registry data (e.g., prospective registration) and publications (e.g., open access). We also obtained summary results reporting rates of due trials registered in the EU Clinical Trials Register (EUCTR) and conducted at German UMCs from the EU Trials Tracker. We developed an interactive dashboard to display these results across all UMCs and at the level of single UMCs. Our study included and assessed 2,895 interventional trials led by 35 German UMCs. Across all UMCs, prospective registration increased from 33% (n = 58/178) to 75% (n = 144/193) for trials registered in ClinicalTrials.gov and from 0% (n = 0/44) to 79% (n = 19/24) for trials registered in DRKS over the period considered. Of trials with a results publication, 38% (n = 714/1,895) reported the trial registration number in the publication abstract. In turn, 58% (n = 861/1,493) of trials registered in ClinicalTrials.gov and 23% (n = 111/474) of trials registered in DRKS linked the publication in the registration. In contrast to recent increases in summary results reporting of drug trials in the EUCTR, 8% (n = 191/2,253) and 3% (n = 20/642) of due trials registered in ClinicalTrials.gov and DRKS, respectively, had summary results in the registry. Across trial completion years, timely results reporting (within 2 years of trial completion) as a manuscript publication or as summary results was 41% (n = 1,198/2,892). The proportion of openly accessible trial publications steadily increased from 42% (n = 16/38) to 74% (n = 72/97) over the period considered. A limitation of this study is that some of the methods used to assess the transparency practices in this dashboard rely on registry data being accurate and up-to-date. In this study, we observed that it is feasible to assess and inform individual UMCs on their performance on clinical trial transparency in a reproducible and publicly accessible way. Beyond helping institutions assess how they perform in relation to mandates or their institutional policy, the dashboard may inform interventions to increase the uptake of clinical transparency practices and serve to evaluate the impact of these interventions.

Using Patient Perspectives to Inform Better Clinical Trial Design and Conduct: Current Trends and Future Directions.

The approach to patient engagement (PE) in drug development has changed rapidly due to many factors, including the complexity of innovative drugs and the need to demonstrate outcomes of relevance to patients, the desire to show 'value add' of PE, and the pandemic-related changes to how clinical trials are run, e.g., decentralised studies. In parallel, there have been changes in technology-assisted ways of running clinical trials, capturing patient health outcomes and preferences, an increasing societal demand for diversity and inclusion, and efforts to improve clinical trial efficiency, transparency, and accountability. Organisations are beginning to monitor PE activities and outcomes more effectively to learn and inform future PE strategies. As a result, these factors are facilitating the incorporation of patients' lived experience, preferences and needs into the design and running of clinical trials more than ever before. In this paper, the authors reflect upon these last few years, the emerging trends and their drivers, and where we may expect PE in clinical research to progress in the near future.

Transparency of clinical trials in pancreatic cancer: An analysis of availability of trial results from the ClinicalTrials.gov database.

Pancreatic cancer (PC) is a highly malignant tumor of the digestive system. As clinical trials involving PC are increasingly being conducted, the transparency of the generated data has become an important issue of concern. In other areas of medicine, clinical trial transparency presents a worrying state of affairs. However, at present, there has been no study examining the transparency of data derived from PC clinicaltrials. A comprehensive search was conducted in the ClinicalTrial.gov database for clinical trials investigating pancreatic cancer as of June 2022. We examined the availability of clinical trial results and recorded the characteristics of the trials. A total of 856 trials were included in this study, of which 668 were completed and 188 were terminated or suspended. The results of 626 trials (73.13%) were available, of these 230 trials (26.87%) did not disclose any information on the trial data in any form. The publication rate for trials with available results was 86.10%, but the report rate on ClinicalTrial.gov was only39.78%. Although approximately 90% of clinical trial investigating interventions on patients with PC have published study results, 30% of trials did not report any findings, and the disclosure of trial results from ClinicalTrial.gov was unsatisfactory. In general, there is still room for improvement in the transparency of PC clinical trials.

Changes resulting from the implementation of the new EU Clinical Trial Regulation 536/2014 from the perspective of patients

The currently valid Regulation (EU) 536/2014 on clinical trials with medicinal products for human use brings some innovations that are of great importance for patients who participate in clinical trials and patients with aneed for innovative therapies. These concern patient protection, especially for vulnerable patient groups, as well as the conditions for further use of data obtained in clinical trials. The introduction of the largely publicly available information system CTIS (Clinical Trials Information System) will significantly improve the transparency of ongoing clinical trials. However, the possibilities of redacting commercially confidential information and postponing the publication of trial-related data and documents for several years may affect the scope of transparency. The request for the sponsor to provide asummary of the protocol and asummary of results of the clinical trial in layman's language (within one year after the end of the trial) also means amassive improvement in transparency for patients, even if this period seems too long, especially for patients with life-threatening diseases. Not all patient-relevant goals originally hoped for have been achieved. The systematic involvement of patients and patient organisations in the clinical trial protocol design is not required by the legislation enacted in 2014. The involvement of patients in the ethical review of the authorisation application dossier is only recommended in the introductory justification, but not codified in the law.

Clinical Trial Registration: What do we need to know?

Trial registration has become an important part of clinical trials and various databases exist across the world. In India, the Clinical Trial Registry India (CTRI) was established in 2007 to promote registration of clinical trials in the country. This initiative which was part of a move to promote transparency in clinical trials has now become a requirement for publication of clinical trials across most journals. This article discusses the importance of clinical trial registration and describes the steps required to complete the registration of a clinical trial in the CTRI database.

Evaluating publication bias for clinical trials supporting new dermatologic drug approvals from 2003 to 2018.

The degree of publication bias and impact of the Food and Drug Administration Amendments Act (FDAAA) of 2007, which aimed to improve clinical trial transparency, has yet to be examined for recent dermatologic drugs. The objective of our study was to estimate the degree of publication bias for clinical trials supporting FDA approval of new dermatologic drugs. This retrospective cohort study examined all phase II and III efficacy trials supporting approval of new dermatologic drugs from 2003 to 2018. FDA drug approval documents were reviewed for supportive clinical trial information, and publications were matched using PubMed and Google Scholar searches. Ratios of relative risks (RRR) comparing positive versus non-positive trials before and after FDAAA enactment served to estimate publication bias. We found that the likelihood of publishing positive versus non-positive drug trials in dermatology was unchanged before and after FDAAA enactment (RRR 0.87, 95% CI 0.37-2.08), as was the likelihood of publishing without misleading interpretation (RRR 1.51, 95% CI 0.22-10.50). There was no measurable publication bias for efficacy trials supporting new drug approvals in dermatology over the past 15years. Fewer pre-FDAAA trials (n = 21) compared to post-FDAAA trials (n = 106) met inclusion criteria. Though not analyzed in this study, safety and secondary efficacy results are other potential sources for publication bias.

Diversity and transparency in gynecologic oncology clinical trials.

Clinical trials advance the standard of care for patients. Patients enrolled in trials should represent the population who would benefit from the intervention in clinical practice. The aim of this study was to assess whether clinical trials enrolling patients with gynecologic cancers report racial and ethnic participant composition and to examine the level of diversity in clinical trials. Using ClinicalTrials.gov, we identified clinical trials enrolling patients with ovarian, uterine/endometrial, cervical, vaginal, and vulvar cancers from 1988 to 2019. Race and ethnicity data were extracted from participant demographics. Descriptive statistics on race, ethnicity, cancer type, location, study status, and sponsor type were calculated. Among trials which reported race and/or ethnicity, sub-analyses were performed on composition of race and ethnicity by funding source, location, and completed study status. A total of 1,882 trials met inclusion criteria; only 179 trials (9.5%) reported race information. Of these, the racial distribution of enrollees was 66.9% White, 8.6% Asian, 8.5% Black/African American, 0.4% Indian/Alaskan Native, 0.1% Native Hawaiian/Pacific Islander, 1.0% more than one race, and 14.5% unknown. Only 100 (5.3%) trials reported ethnicity. Except for trials enrolling patients with cervical cancer which enrolled 65.2% White and 62.1% Non-Hispanic/Latino/a patients, enrollees in trials for other gynecologic cancers were over 80% White and 88% Non-Hispanic/Latino/a. Industry funded trials enrolled higher proportions of White (68.4%) participants than non-industry funded trials (57.5%). Domestic trials report race (11.5%) and ethnicity (7.6%) at higher rates than international trials (6.9% and 2.3%, respectively). Reporting of race (1.7% vs. 13.9%) and ethnicity (1.7% vs. 11.1%) has increased over time for patients enrolled in 2000 vs. 2018. Less than 10% of trials enrolling patients with gynecologic malignancies report racial/ethnic participant composition on ClinicalTrials.gov. Accurate reporting of participant race/ethnicity is imperative to ensuring minority representation in clinical trials.