Expanded Access Programs, compassionate drug use, and Emergency Use Authorizations during the COVID-19 pandemic.
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ABSTRACT:
SUBMITTER: Rizk JG
PROVIDER: S-EPMC7694556 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and aimsDuring the COVID-19 pandemic, US Food and Drug Administration (FDA) permitted emergency use authorizations (EUAs) for vaccines/treatments with promising data. Eight treatments were issued EUAs by May 31, 2021; one of these was approved (Remdesivir for certain populations) and two were revoked (chloroquine phosphate/hydroxychloroquine and bamlanivimab) by September 30, 2021. The aim of this study is to find out what evidence the EUAs were based on and how many studies were published while they remained active (up to September 30, 2021).MethodsA review of published clinical studies for the 6 months before each EUA was issued, and the time after (until September 30, 2021, or until revoked). PubMed and the identified systematic reviews were the sources for identifying published literature.ResultsThe number of clinical studies published pre-EUA varied from a single case study (for chloroquine phosphate/hydroxychloroquine) to numerous studies of multiple types (for convalescent plasma). Four treatments had a single randomized controlled trial (RCT) as evidence (bamlanivimab monotherapy, REGN-COV, bamlanivimab + etesevimab, sotrovimab) and two also had other study types (remdesivir and baricitinib). The number of clinical studies published post-EUA (for those active on September 30, 2021) was widely varied. Eighteen RCTs were published for Convalescent plasma, while Remdesivir had eight. Baricitinib, REGN-COV, and bamlanivimab + etesevimab all had one, but none were published for sotrovimab.ConclusionThe number of trials for treatments with EUAs was limited in all cases before the EUA was issued, and in most cases for those with EUAs ongoing at the end of September 2021. The presence of EUAs may discourage participation in relevant clinical trials, which delays the widespread implementation of evidenced-based therapies. Large, robust RCTs should be completed, such as the RECOVERY trial in the United Kingdom, to quickly find the answers desperately required during a pandemic.
| S-EPMC9831114 | biostudies-literature
Project description:Background The world is facing an unprecedented outbreak affecting all aspects of human lives which is caused by the COVID-19 pandemic. Due to the virus novelty, healthcare systems are challenged by a high rate of patients and the shortage of medical products. To address an increased need for essential medical products, national authorities, worldwide, made various legislative concessions. This has led to essential medical products being produced by automotive, textile and other companies from various industries and approved under the emergency use authorizations or legal concessions of national regulatory bodies. This paper presents a narrative commentary of the available documentation on emergency use authorizations and legal concessions for medical products during COVID-19 pandemic. Methodology The basis for narrative commentary includes scientific articles published in Web of Science, Scopus, PubMed and Embase databases, official publications of international organizations: Food and Drug Agency (FDA), World Health Organisation (WHO), World Bank and United Nations (UN), and national regulatory agency reports in native languages (English, German, Bosnian, and Croatian) published from November 1, 2019 to May 1, 2020. This paper focuses on three types of essential medical products: mechanical ventilators, personal protective equipment (PPE) and diagnostic tests. Evidence-informed commentary of available data and potential identified risks of emergency use authorizations and legal concessions is presented. Discussion It is recognized that now more than ever, raising global awareness and knowledge about the importance of respecting the essential requirements is needed to guarantee the appropriate quality, performance and safety of medical products, especially during outbreak situation, such as the COVID-19 pandemic. Emergency use authorizations for production, import and approval of medical products should be strictly specified and clearly targeted from case to case and should not be general or universal for all medical products, because all of them are associated with different risk level. Conclusion Presented considerations and experiences should be taken as a guide for all possible future outbreak situations to prevent improvised reactions of national regulatory bodies.
| S-EPMC7530883 | biostudies-literature
Project description:IntroductionConcomitant experimental/compassionate drug administration has been all-pervasive in the treatment of COVID-19 patients. The objective of this study was to study the relationship between patient severity, the number of experimental/compassionate medications received (main outcome measure), and patient outcomes [survival to hospital discharge and length of hospital stay (LOS)].MethodsRetrospective analysis of data collected in real time during the first pandemic wave in a tertiary care hospital. Data included patient demographics, comorbidities, admission vital signs, laboratory values, most extreme respiratory intervention during hospitalization, and data regarding treatment with compassionate/experimental drugs during their stay.ResultsOverall, 292 PCR-confirmed patients with symptoms of COVID-19 were studied (March/April, 2020). Increasing respiratory support correlated with both LOS and mortality. Patients were more likely to receive more than 1 experimental/compassionate drugs as respiratory support escalated, ranging from 3% (n = 4/136) among patients on room air to 77.3% (n = 17/22) of mechanically ventilated/ECMO patients (P < 0.001, linear by linear association). The mean number of experimental/compassionate drugs received also increased with escalating respiratory support (P < 0.001, one-way ANOVA). After adjustment for severity of patient condition, administration of more experimental/compassionate drugs was unrelated to survival (P = 0.24), but was related to increased LOS (P < 0.001).ConclusionPatients that were hospitalized in worse condition were more likely to receive more experimental/compassionate drugs. Treatment was unrelated to survival but may have been related to LOS. This finding raises questions regarding the results of studies on medication effects that adjusted for multiple drug administration.
| S-EPMC8381349 | biostudies-literature
Project description:We examined factors that may impact cabazitaxel treatment duration in a real-life setting in a compassionate use program, expanded access program, and prospective observational study in metastatic castration-resistant prostate cancer (mCRPC). Patients with mCRPC previously treated with docetaxel (N = 1,621) received cabazitaxel 25 mg/m2 intravenously every 3 weeks until disease progression, death, unacceptable toxicity or physician/patient decision. The median number of cabazitaxel cycles was six (range, 1-49); 708 patients (43.7%) received >6 cycles. Patients receiving >6 cycles tended to have a better Eastern Cooperative Oncology Group performance status of 0-1 (p = 0.0017 for ?6 vs. >6 cycles). Overall, 348 patients (21.5%) were ?75 years of age; 139 (39.9%) received >6 cycles. The main reason for discontinuation was disease progression; however, in patients receiving 1-2 cycles, the main reason for discontinuation was adverse events. Only 52 patients (3.2%) progressed during cycles 1-2. Cabazitaxel was well tolerated in these studies, which included some elderly and frail patients, offering clinicians an important treatment option in the management of mCRPC. Proactive management of adverse events may allow patients to receive a higher number of cabazitaxel cycles and derive greater benefit.
| S-EPMC7226228 | biostudies-literature
Project description:BackgroundNew emerging infections have no known treatment. Assessing potential drugs for safety and efficacy enables clinicians to make evidence-based treatment decisions and contributes to overall outbreak control. However, it is difficult to launch clinical trials in the unpredictable environment of an outbreak. We conducted a bibliometric systematic review for the 2009 influenza pandemic to determine the speed and quality of evidence generation for treatments. This informs approaches to high-quality evidence generation in this and future pandemics.MethodsWe searched PubMed for all clinical data (including clinical trial, observational and case series) describing treatment for patients with influenza A(H1N1)pdm09 and ClinicalTrials.gov for research that aimed to enrol patients with the disease.ResultsThirty-three thousand eight hundred sixty-nine treatment courses for patients hospitalised with A(H1N1)pdm09 were detailed in 160 publications. Most were retrospective observational studies or case series. Five hundred ninety-two patients received treatment (or placebo) as participants in a registered interventional clinical trial with results publicly available. None of these registered trial results was available during the timeframe of the pandemic, and the median date of publication was 213 days after the Public Health Emergency of International Concern ended.ConclusionPatients were frequently treated for pandemic influenza with drugs not registered for this indication, but rarely under circumstances of high-quality data capture. The result was a reliance on use under compassionate circumstances, resulting in continued uncertainty regarding the potential benefits and harms of anti-viral treatment. Rapid scaling of clinical trials is critical for generating a quality evidence base during pandemics.
| S-EPMC7441224 | biostudies-literature
Project description:BackgroundAn increase in the number of people presenting to emergency departments (EDs) is contributing to ED overcrowding. In the early stages of the COVID-19 pandemic, there was a significant reduction in the number of ED presentations in Australia, creating an opportunity to learn from patients' experiences of alternative management options.ObjectiveThe aim of this study is to report on the use and experience of health services by Australian adults experiencing a health issue during the COVID-19 pandemic for which they would have presented at an ED prior to the pandemic.MethodsAn online survey was conducted in May 2020. Reported health issues were categorized using an existing classification system. Data collected included demographics, care pathways, levels of concern at times of health issue and survey completion, and patient-reported experiences with care.ResultsA total of 1289 eligible respondents completed the survey. Almost 25% (309/1289) of respondents avoided an ED presentation, of which 58% (179/309) used an alternative form of health care and 42% (130/309) self-managed. Respondents making face-to-face or telehealth appointments with their general practitioner (GP) reported high levels of ED avoidance (135/286, 47%) and mostly positive experiences of care provided by GPs. A high proportion of those who self-managed reported high levels of concern at the time of completing the survey (42/130, 32%).ConclusionsTelehealth consultations with GPs may be a more promotable alternative to the ED beyond the COVID-19 pandemic, providing easier access to a doctor with access to patients' medical histories than an appointment for a face-to-face consultation. GP telehealth consultations may also address barriers to accessing health care for those with potentially the greatest need. The reported use and positive experiences with GP telehealth appointments should inform further research on their appropriateness as an alternative to the ED.
| S-EPMC8428819 | biostudies-literature
Project description:Belantamab-mafodotin (belamaf) is a novel antibody-drug conjugate targeting B-cell maturation antigen that showed anti-myeloma activity in patients with relapsed and refractory multiple myeloma (RRMM). We performed an observational, retrospective, and multicenter study aimed to assess the efficacy and safety of single-agent belamaf in 156 Spanish patients with RRMM. The median number of prior therapy lines was 5 (range, 1-10), and 88% of patients were triple-class refractory. Median follow-up was 10.9 months (range, 1-28.6). The overall response rate was 41.8% (≥CR 13.5%, VGPR 9%, PR 17.3%, MR 2%). The median progression-free survival was 3.61 months (95% CI, 2.1-5.1) and 14.47 months (95% CI, 7.91-21.04) in patients achieving at least MR (p < 0.001). Median overall survival in the entire cohort and in patients with MR or better was 11.05 months (95% CI, 8.7-13.3) and 23.35 (NA-NA) months, respectively (p < 0.001). Corneal events (87.9%; grade ≥ 3, 33.7%) were the most commonly adverse events, while thrombocytopenia and infections occurred in 15.4% and 15% of patients, respectively. Two (1.3%) patients discontinued treatment permanently due to ocular toxicity. Belamaf showed a noticeably anti-myeloma activity in this real-life series of patients, particularly among those achieving MR or better. The safety profile was manageable and consistent with prior studies.
| S-EPMC10251953 | biostudies-literature
Project description:BackgroundAlthough expanded access is an increasingly used pathway for patients to access investigational medicine, little is known on the magnitude and content of published scientific research collected via expanded access.MethodsWe performed a review of all peer-reviewed expanded access publications between January 1, 2000 and January 1, 2022. We analyzed the publications for drugs, diseases, disease area, patient numbers, time, geographical location, subject, and research methodology (single center/multicenter, international/national, prospective/retrospective). We additionally analyzed endpoints reported in all COVID-19-related expanded access publications.ResultsWe screened 3810 articles and included 1231, describing 523 drugs for 354 diseases for 507,481 patients. The number of publications significantly increased over time ([Formula: see text]). Large geographical disparities existed as Europe and the Americas accounted for 87.4% of all publications, whereas Africa only accounted for 0.6%. Oncology and hematology accounted for 53% of all publications. Twenty-nine percent of all expanded access patients (N = 197,187) reported on in 2020 and 2021 were treated in the context of COVID-19.ConclusionsBy summarizing characteristics of patients, diseases, and research methods described in all scientific literature published on expanded access, we provide a unique dataset for future research. We show that published scientific research on expanded access has surged over the past decades, partly due to COVID-19. However, international collaboration and equity in geographic access remain an issue of concern. Lastly, we stress the need for harmonization of research legislation and guidance on the value of expanded access data within real-world data frameworks to improve equity in patient access and streamline future expanded access research.
| S-EPMC10193319 | biostudies-literature
Project description:Tuberculosis (TB) remains a global emergency and is one of the most common infectious disease causes of death in developing countries. Current treatment regimens for multi-drug resistant TB are associated with low treatment success rates, are toxic, and require long duration of treatment. The need for shorter and more effective treatment regimens is urgent. Delamanid (Deltyba, or formerly known as OPC-67683) is a new dihydro-imidazooxazole anti-TB drug active against resistant forms of pulmonary TB. Delamanid kills Mycobacterium tuberculosis by inhibiting the synthesis of mycolic acids required for cell wall synthesis. Whilst delamanid has been included in the WHO Model List of Essential Medicine by the World Health Organization Expert Committee on Selection and Use of Essential Medicines and in international guidance for the treatment of multi-drug resistant TB since April 2014, its access in countries with the greatest need, has proven challenging. This review provides an update on currently available clinical safety and efficacy data on delamanid and offers a discussion on research priorities and recommendations for expedited, expanded access.
| S-EPMC4631416 | biostudies-other
Project description:Children represent a minority of total COVID-19 cases, but studies have reported severe disease and death in pediatric patients. Remdesivir (RDV) has recently demonstrated promising results in adults with COVID-19, but few data have been reported to date in children.A nationwide multicenter observational study was conducted on children with confirmed SARS-CoV-2 receiving compassionate treatment with RDV in Spain. Eight patients were included in the study, four infants and four older children [median age 5 years old; IQR 4 months-11.6 years old]. Half of them had complex underlying medical conditions, and the rest were mostly infants (3/4). Six out of eight children needed Pediatric Intensive Care Unit Admission. No RDV-related adverse outcomes were observed in our patients. Seven have reached successful clinical outcome, but one patient with serious clinical status died due to complications. However, she received RDV very late after the first COVID-19 symptom.Conclusions: In our cohort, most of the patients achieved successful clinical outcome, without observing adverse events. Clinical trials of RDV therapy for children with COVID-19 are urgently needed, to assess the safety, tolerability, efficacy, and pharmacokinetics of RDV in children, as this could be an effective treatment in severe cases. What is Known: • Remdesivir has not been approved to treat COVID-19 in children under 12 years old, although the drug is currently being prescribed in critically ill children. • Remdesivir has recently demonstrated promising results in adults with COVID-19, but few data have been reported to date in paediatric population. What is New: • We report a multicentre cohort of children with confirmed SARS-CoV-2 and severe COVID-19 disease receiving remdesivir during the first month of the pandemic in Spain. • No remdesivir-related adverse outcomes were observed in most of the cases. Seven patients reached successful clinical outcome, and one died due to complications (bacterial sepsis).
| S-EPMC7668659 | biostudies-literature