ClinicalTrials.gov as a Source of Information About Expanded Access Programs: Cohort Study

Abstract

Background ClinicalTrials.gov (CT.gov) is the most comprehensive internet-based register of different types of clinical studies. Expanded access is the use of unapproved drugs, biologics, or medical devices outside of clinical trials. One of the key problems in expanded access is the availability to both health care providers and patients of information about unapproved treatments. Objective We aimed to evaluate CT.gov as a potential source of information about expanded access programs. Methods We assessed the completeness of information in the records of 228 expanded access programs registered with CT.gov from February 2017 through May 2020. Moreover, we examined what percentage of published expanded access studies has been registered with CT.gov. Logistic regression (univariate and multivariate) and mediation analyses were used to identify the predictors of the absence of some information and a study’s nonregistration. Results We found that some important data were missing from the records of many programs. Information that was missing most often included a detailed study description, facility information, central contact person, and eligibility criteria (55.3%, 54.0%, 41.7%, and 17.5% of the programs, respectively). Multivariate analysis showed that information about central contact person was more likely to be missing from records of studies registered in 2017 (adjusted OR 21.93; 95% CI 4.42-172.29; P<.001). This finding was confirmed by mediation analysis (P=.02). Furthermore, 14% of the programs were registered retrospectively. We also showed that only 33 of 77 (42.9%) expanded access studies performed in the United States and published from 2014 through 2019 were registered with CT.gov. However, multivariate logistic regression analysis showed no significant association between any of the variables related to the studies and the odds of study nonregistration (P>.01). Conclusions Currently, CT.gov is a quite fragmentary source of data on expanded access programs. This problem is important because CT.gov is the only publicly available primary source of information about specific programs. We suggest the actions that should be taken by different stakeholders to fully exploit this register as a source of information about expanded access.

Characteristics of the Compassionate Use Program in Japan: An Analysis of Expanded Access Clinical Trials from 2016 to 2021

“…In the future, we hope that by resolving issues arising from the differences and similarities noted in the comparison between the Japanese and EU/US systems, effective drugs will be made accessible to patients at the earliest opportunity. In the United States, the Right to Try Act 17 encourages sponsors to make investigational medicines available earlier in the clinical development period, partly because it shields them from any liability associated with patient injury because of expanded access 35,36 . Undeniably, the CU program seeks to strike a balance between providing patients with access to unapproved drugs and treatments, protecting them from unreasonable toxicity or danger, and collecting patient safety data from patients as they take new medications.…”

“…In the United States, the Right to Try Act 17 encourages sponsors to make investigational medicines available earlier in the clinical development period, partly because it shields them from any liability associated with patient injury because of expanded access. 35,36 Undeniably, the CU program seeks to strike a balance between providing patients with access to unapproved drugs and treatments, protecting them from unreasonable toxicity or danger, and collecting patient safety data from patients as they take new medications. However, in Japan, we recommend establishing a singlepatient EACT system and implementing an emergency system, like the CU systems in the United States and the European Union.…”

Where are caregivers in the clinical trial? Evaluation of caregiver responsibilities in Alzheimer's disease and related dementias clinical trials

“…We conducted a scoping review of ADRD clinical trials completed between 1990 and 2021 using clinicaltrials.gov. We focused our analysis on clinicaltrials.gov given that it is considered the most comprehensive database of clinical studies 18 . Our search terms included “dementia,” “Alzheimer's,” and “Alzheimer's dementia”; 258 initial entries matched at least one of the search criteria.…”

“…Their role may be amplified in recruiting racial and ethnic minority older adults with ADRD, for instance, in translating trial information and advocating for culturally appropriate ADRD screening and diagnostic tools used to determine eligibility for clinical trials 14–17 . Caregivers may obtain this information directly or indirectly (e.g., from clinicians) from prominent sources such as clinicaltrials.gov 18 . Yet, little is known about what responsibilities caregivers are expected to uphold within the context of clinical trials, and how these roles and responsibilities are conveyed to prospective clinical trial participants and their caregivers.…”

“…[14][15][16][17] Caregivers may obtain this information directly or indirectly (e.g., from clinicians) from prominent sources such as clinicaltrials.gov. 18 givers make decisions about enrolling their relative in a clinical trial. 16 With a better understanding of what caregivers are expected to do in supporting their relative through clinical trials, we can develop appropriate resources and supports for caregivers through the clinical trial process.…”