Therapeutic innovation & regulatory science最新文献

The National Medical Products Administration of China has been implementing ICH E17, which describes the general principles for planning and designing of multi-regional clinical trials (MRCTs), yet there are several ambiguities in the execution and conduct remains in China or East Asia. In specific, pooling strategy, effect modifiers (EMs), statistical analysis, sample size allocation and their impact in alignment with global trial remains a challenge. In this paper, we explore on the criteria mentioned above under the context of China. EMs need to be determined and identified from intrinsic and extrinsic factors which might have the impact to the drug on specific populations. If no EMs are found, we use pooling by regions to understand whether differences across East Asian population exists, and whether pooling by East Asian is necessary. Statistical models used in the analysis are also listed to estimate the drug effect in pooled populations. In summary, this paper outlines the details of the MRCTs practices in China and provides better insights in practice both domestically and internationally for any future improvements.

Medicine is increasingly supported by software, with digital health technologies offering innovative ways to capture insights and drive therapies. Globally, medical device software must follow regulatory processes based on risk classification. The introduction of MDR represents a significant shift in risk-based classification for Medical Devices in Europe, including classification Rule 11 for software, which has caused significant discussions among European regulators. Three years after implementation, we conducted a systematic impact assessment of MDR classification Rule 11 for MDSW through a qualitative and quantitative analysis of over 2000 software entries from the European Medical Device database, complemented by data from other public databases such as the German DiGA directory and mHealthBELGIUM. Our results indicate that classification Rule 11 of the MDR results in a narrow bandwidth for class I software, whereas this used to be the most frequent classification for software under the MDD: while most of legacy software in EUDAMED falls in the lowest risk category as MDD Class I (53%), the situation reverses after the implementation of MDR with the most entries in Class IIa (55%). Analyzing the legacy MDD patient apps in Germany implies that three quarters will have to re-classify as MDR Class IIa at the end of the transition period in 2028. A comparison of the European and US regulatory landscapes, along with a systematic review of software features for Class I vs. Class IIa products, explains our findings and enables us to recommend a regulatory strategy for developing MDSW compliant with MDR Class I rules, ensuring fast access to the European market.

Since 2019, the Association of Clinical Research Organizations has conducted a landscape survey of risk based quality management (RBQM) adoption in clinical trials. Here, we present data from four years of surveys, with an emphasis on the most recent: the 2022 survey included data from 4958 trials across seven contract research organizations, of which 1004 were new studies started in 2022. Results indicate that while overall risk assessment adoption is strong, it is lagging in other risk-based components which suggests companies are not deriving the full expected benefits of performing a risk assessment and mitigation process to their trials. The 2022 study also suggests new study starts showing promising traction, with adoption hovering near 50% for most RBQM elements. At the same time, the survey suggests industry has mixed views on the potential value of quality tolerance limits (QTLs). Ultimately, centralized monitoring is being underutilized despite the potential of increased patient safety oversight and improved data quality. The authors of this paper developed a case study based on a trial in clinicaltrials.gov to demonstrate how RBQM adoption could include the key RBQM elements such as centralized monitoring, reduced source data review and source data verification as well as implementation of QTLs in a real-world scenario. The authors believe the clinical trial industry has an obligation to utilize centralized monitoring to produce more efficient and effective clinical trials and will make a case to do so in this paper.

In the International Council for Harmonisation (ICH) guidance on General Principles for Planning and Design of Multi-Regional Clinical Trials (E17), it is important to evaluate the consistency of treatment effect across regions in a multi-regional clinical trial (MRCT). In this paper, we elaborated on some basic considerations to evaluate consistency. We first list the design considerations, and then provide consistency evaluation and interpretation on pharmacokinetics, pharmacodynamics, efficacy, safety, and benefit-risk. Furthermore, we consider special situations including non-inferiority, multiple primary endpoints, interim analyses with delayed treatment effect, adaptive design, single-arm studies, rare diseases, and statistical methods for regional treatment effect estimate and consistency evaluation. Finally, if potential inconsistency is anticipated or observed in the MRCT, an exploratory framework is provided for further investigations. Overall, this paper elaborates on consistency evaluation in MRCT, discusses possible challenges in reality and also provides strategies and methods to overcome these challenges. This could help consensus across health authorities, industries, and academic societies, which could further facilitate consistency evaluation and MRCT implementation. Effective communication with regulatory authorities is encouraged to obtain an acceptance of a global approach.

It has long been a basic principle of randomized clinical trials addressing serious outcomes and/or major public health issues that interim data should be inaccessible to investigators and to industry sponsors, with interim data reviewed on a regular basis by an independent data monitoring committee (DMC). Challenges to this principle may arise when sponsors and/or regulators perceive a need to review interim data while the trial remains ongoing-for example, when a trial is being considered for accelerated approval. In this paper we propose approaches that could minimize the extent of interim data that is made available to others while the trial continues.

The Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017 signed on May 30, 2018 under President Trump has been championed by patient advocacy groups as a victory for individuals with life threatening illnesses willing to undergo experimental treatment. The act is not a novel idea, but rather a nuanced result of the previous attempts to challenge the US Food and Drug Administration's (FDA) authority on drug approval and distribution. Currently, right-to-try programs coexist with an already existing expanded access program run by the FDA. The difference is that right-to-try requests eliminate FDA guidance and authorization. The objectives of this study are to review prior historical challenges to the FDA and how they eventually influenced right-to-try movements, examine the law itself and its arguments written by advocates and critics, discuss how its implications fit into the current climate of regulatory flux, and propose the impacts it has on influencing patient care and the scientific process.

Background: Prescription drugs may be indicated to treat more than one medical condition, and companies may promote more than one indication in the same direct-to-consumer (DTC) ad. This study examined how presenting multiple prescription drug indications in one DTC television ad affects consumers' processing of drug information.

Methods: We conducted two studies with adults diagnosed with diabetes (Study 1, N = 408) or rheumatoid arthritis (Study 2, N = 411). We randomly assigned participants to view one of three television ads: primary indication only (Study 1: diabetic peripheral neuropathy; Study 2: rheumatoid arthritis), primary plus a similar secondary indication (Study 1: fibromyalgia; Study 2: psoriatic arthritis), or primary plus a dissimilar secondary indication (Study 1: generalized anxiety disorder; Study 2: ulcerative colitis).

Results: Remembering and understanding the primary indication was not significantly affected by the presence of a secondary indication (similar or dissimilar). Higher health literacy participants remembered and understood secondary indications.

Conclusions: Including a second indication in DTC television ads does not appear to have detrimental effects and can increase awareness of the second indication for some participants. Industry and regulators should continue to ensure DTC promotion is truthful and non-misleading, irrespective of the number of indications presented.