Dataset Information

Preclinical efficacy in therapeutic area guidelines from the U.S. Food and Drug Administration and the European Medicines Agency: a cross-sectional study.

ABSTRACT: BACKGROUND AND PURPOSE:Therapeutic area guidelines (TAGs) published by the EMA and the FDA offer guidance in planning the launch of a trial in a certain indication. We assessed and compared the guidance on preclinical efficacy of all available TAGs from EMA and FDA. EXPERIMENTAL APPROACH:EMA and FDA websites and databases were searched for all TAGs. A mixed deductive and inductive approach was applied to analyse and cluster content for preclinical efficacy. KEY RESULTS:A total of 114 EMA and 120 FDA TAGs were identified, covering 126 indications. Our core finding is that 75% of EMA TAGs and 58% from the FDA TAGs do not offer any guidance on preclinical efficacy. TAGs varied widely on the extent, nature and detail of guidance. CONCLUSIONS AND IMPLICATIONS:Guidance on preclinical efficacy in a consistent, comprehensive and explicit way that still allows for justified deviations is an important but neglected aspect of transparency for drug development. This transparency would help sponsors in designing preclinical studies and in negotiating more efficiently with regulators.

SUBMITTER: Langhof H

PROVIDER: S-EPMC6193882 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Preclinical efficacy in therapeutic area guidelines from the U.S. Food and Drug Administration and the European Medicines Agency: a cross-sectional study.

Langhof Holger H Chin William Wei Lim WWL Wieschowski Susanne S Federico Carole C Kimmelman Jonathan J Strech Daniel D

British journal of pharmacology 20181001 22

<h4>Background and purpose</h4>Therapeutic area guidelines (TAGs) published by the EMA and the FDA offer guidance in planning the launch of a trial in a certain indication. We assessed and compared the guidance on preclinical efficacy of all available TAGs from EMA and FDA.<h4>Experimental approach</h4>EMA and FDA websites and databases were searched for all TAGs. A mixed deductive and inductive approach was applied to analyse and cluster content for preclinical efficacy.<h4>Key results</h4>A to ...[more]

PMID: 30153701

Similar Datasets

Project description:BackgroundPrompted by the Covid-19 pandemic and the need to ensure timely and safe access to medicines during a pandemic, the aim of this study was to compare and contrast the EU and US regulations, processes, and outcomes pertaining to the granting of accelerated Marketing Authorizations (MAs) for COVID-19 vaccines and treatments with a view to determining how effective these regulations were in delivering safe medicines in a timely manner.MethodsMAs for medicines approved for Covid-related indications in the first two pandemic years (March 2020-February 2022) were identified using the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) websites. Authorization reports and utilized regulations were reviewed to determine and compare approval timelines, facilitated pathways, accepted clinical evidence, and effectiveness of the regulations by assessing them against time and safety standards.ResultsBy the end of February 2022, the EMA and FDA had granted 12 and 14 MAs, respectively. Two EU and two US approvals were issued in relation to new indications for already-approved treatments; the remaining ones were first-time approvals of novel vaccines and treatments. The median time to approval was 24 days for the EMA's conditional MAs and 36 days for the USFDA's Emergency Use Authorizations (EUA) for all Covid-19 medicines. This is compared with 23 and 28 days, respectively, specifically for first-time novel vaccines and treatments authorized by both USFDA and EMA. The USFDA and EMA differed markedly in terms of the time taken to approve new indications of already-approved treatment; the USFDA took 65 days for such approval, compared with 133 days for the EMA. Where MAs were issued by both authorities, USFDA approvals were issued before EMA approvals; applications for approval were submitted to the FDA before submission to the EMA. Three EU and two US MAs were based on data from two or more phase 3 clinical trials; the remaining ones were based on single trial data. Only six EU and four US trials had been completed by the time of authorization. This was in line with regulations. While the applicable regulations shared many similarities, there were marked differences. For instance, the EU's conditional MA regulation pertains only to first approvals of new treatments. It does not cover new indications of already-approved treatments. This contrasts with the US, where the EUA regulation applies to both types of applications, something that may have impacted approval timelines. Overall, both EU and US utilized regulations were considered to be effective. For most cases, utilizing such regulations for Covid-19 MAs resulted in faster approval timelines compared to standard MAs. They were flexible enough to manage the process of granting emergency approvals while maintaining strict requirements and allowing comprehensive reviews of the supporting evidence.ConclusionUS and EU regulations were effective in ensuring timely accelerated market access to Covid-19 medicines during the pandemic without compromising the approval standards related to safety or efficacy. The population in both regions will receive comparable access to medicines during a pandemic if sponsors submit their applications to both authorities in parallel.

Project description:ImportanceFor patients with cancer treated with palliative intent, quality of life (QOL) is a critical aspect of treatment decision-making, alongside survival. However, regulatory approval can be based solely on survival measures or antitumor activities, without QOL evidence.ObjectiveTo investigate whether recently approved oncology therapies demonstrate clinically meaningful improvements in QOL.Evidence reviewThis systematic review study identified oncology drug indications approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) from January 2006 to December 2017 and supporting clinical trials (QOL publications identified to October 2019). Indications were evaluated for the presence of published QOL evidence; QOL benefits according to the American Society of Clinical Oncology Value Framework version 2.0 (ASCO-VF) and European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS) QOL bonus criteria; and clinically meaningful improvements in QOL beyond minimal clinically important differences. Hematology trials were not evaluated by ESMO-MCBS. Associations between QOL evidence and approval year were examined using logistic regression models.FindingsIn total, 214 FDA-approved (77 [36%] hematological) and 170 EMA-approved (52 [31%] hematological) indications were included. QOL evidence was published for 40% and 58% of FDA- and EMA-approved indications, respectively. QOL bonus criterion for ASCO-VF and ESMO-MCBS was met in 13% and 17% of FDA-approved and 21% and 24% of EMA-approved indications, respectively. Clinically meaningful improvements in QOL beyond minimal clinically important differences were noted in 6% and 11% of FDA- and EMA-approved indications, respectively. Availability of published QOL evidence at the time of approval increased over time for EMA (odds ratio [OR], 1.13; P = .03), however not for FDA (OR, 1.10; P = .12). Over time, no increase in awarded QOL bonuses or clinically meaningful improvements in QOL were found.Conclusions and relevanceThe findings of this systematic review suggest that approved systemic oncology therapies often do not have published evidence to suggest QOL improvement, despite its recognized importance. Of indications with evidence of statistical improvement, few have demonstrated clinically meaningful improvements.

Project description:ObjectivesStratified medicine is often heralded as the future of clinical practice. Key part of stratified medicine is the use of predictive biomarkers, which identify patient subgroups most likely to benefit (or least likely to experience harm) from an intervention. We investigated how many and what predictive biomarkers are currently included in European Medicines Agency (EMA) licensing.SettingEMA licensing.ParticipantsIndications and contraindications of all drugs considered by the EMA and published in 883 European Public Assessment Reports and Pending Decisions.Primary and secondary outcome measuresData were collected on: the type of the biomarker, whether it selected a subgroup of patients based on efficacy or toxicity, therapeutic area, marketing status, date of licensing decision, date of inclusion of the biomarker in the indication or contraindication and on orphan designation.Results49 biomarker-indication-drug (B-I-D) combinations were identified over 16 years, which included 37 biomarkers and 41 different drugs. All identified biomarkers were molecular. Six drugs (relating to 10 B-I-D combinations) had an orphan designation at the time of licensing. The identified B-I-D combinations were mainly used in cancer and HIV treatment, and also in hepatitis C and three other indications (cystic fibrosis, hyperlipoproteinaemia type I and methemoglobinaemia). In 45 B-I-D combinations, biomarkers were used as predictive of drug efficacy and in four of drug toxicity. It appeared that there was an increase in the number of B-I-D combinations introduced each year; however, the numbers were too small to identify any trends.ConclusionsGiven the large body of literature documenting research into potential predictive biomarkers and extensive investment into stratified medicine, we identified relatively few predictive biomarkers included in licensing. These were also limited to a small number of clinical areas. This might suggest a need for improvement in methods of translation from laboratory findings to clinical practice.

Dataset Information

Preclinical efficacy in therapeutic area guidelines from the U.S. Food and Drug Administration and the European Medicines Agency: a cross-sectional study.

Publications

Preclinical efficacy in therapeutic area guidelines from the U.S. Food and Drug Administration and the European Medicines Agency: a cross-sectional study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets