The article review the challenges and lack of robust biologics market competition and drug pricing impacts, the history of the small molecule generics marketplace and the subsequent early evolution of the biosimilar marketplace. The article then explores the potential of an abbreviated biologics license application pathway to market-akin to the market entry pathway for generics-as a policy lever for improving biologics drug price competition, drug affordability and expanded access.

In cancer research, multiple primary study endpoints, which may be correlated, are often considered. In practice, it is common to evaluate each clinical endpoint separately when performing sample size calculations. However, when the endpoints are correlated, treating them independently may lead to conservative sample size requirements. In this article, alternatively, we consider power calculation based on linear combination of two correlated clinical outcomes (e.g., binary responses) to address the correlation between them. For simplicity and for illustrational purpose, sample size formulae will be derived under hypothesis testing for non-inferiority. The results are evaluated both theoretically and via numerical studies. The results indicate that the required sample size is highly sensitive to the correlation between endpoints (ρ), event probabilities (p1, p2), and the non-inferiority margin (δZ). Stronger correlation increases informational redundancy and weakens the effective signal, raising the sample size requirement; when event rates are equal, variance is maximized, resulting in the highest sample size; conversely, a larger non-inferiority margin-implying greater tolerance for treatment differences-significantly reduces sample size. The weights (a, b) assigned to the composite endpoint are also crucial. With equal endpoint effects, balanced weights lower variance and reduce sample size, while unequal weights raise variance and increase sample size. Moreover, the assumed direction of treatment effects can substantially influence non-inferiority conclusions and the required sample size (e.g., [Formula: see text] vs. [Formula: see text]).

Clinical trials are conducted under rigorous ethical and regulatory frameworks to protect participants, including ethics committee approval, informed consent, oversight, and personal data protection. However, public awareness of these safeguards in Poland remains insufficiently studied. We conducted a nationwide cross-sectional survey via computer-assisted web interviews with 1200 adults in Poland (January 2023). Awareness was defined as agreement with statements reflecting ethical and regulatory safeguards; "high awareness" indicated endorsement of at least 7 out of 9 items. A questionnaire covered nine core principles of clinical trials, including ethical review, informed consent, participant rights, and data protection. Descriptive statistics, chi-square tests, and logistic regression identified factors associated with high awareness (≥ 7/9 endorsed items). Awareness was generally high: 88.1% recognised the need for trials to introduce new drugs and 83.7% knew that informed consent was required. However, gaps in knowledge regarding regulatory oversight and data protection were identified. In the final multivariable logistic regression model, lower education was associated with reduced odds of high awareness (secondary vs. higher: aOR = 0.56; post-secondary vs. higher: aOR = 0.54), as was uncertainty about prior clinical trial participation ("do not know" vs. no: aOR = 0.55). Model discrimination was limited (AUC = 0.59). Awareness of core ethical safeguards, such as informed consent, was high, but gaps remained in regulatory oversight and data protection. Education was the strongest correlate, indicating a need for targeted communication.

The new European Union Joint Clinical Assessment (JCA) process, effective January 2025, requires pharmaceutical companies to submit evidence within 100 days of notification. Key challenges include uncertainty about PICO (Population, Intervention, Comparator, Outcomes) parameters prior to PICO notification, limited timeframe for evidence generation, and need to reconcile differences between regulatory versus health technology assessment (HTA) evidence standards. Uncertainties involve predicting PICOs accurately and determining real-world evidence's (RWE) appropriate role. However, opportunities exist for integrated evidence planning across clinical development, regulatory, and health economics and outcomes research (HEOR) teams, leveraging real-world data to inform or address PICOs as well as support regulatory evidence requirements. Early alignment between key functional teams, combined with proactive RWE use, is essential for generating fit-for-purpose evidence that satisfies the dual scrutiny of regulatory approval and HTA relative effectiveness assessment.

This review examines Japan's 2025 revision of bioequivalence (BE) guidelines for semi-solid topical dermatological drug products as a case study in regulatory science, focusing on how accumulated scientific evidence has been translated into regulatory decision-making frameworks, which scientifically refines Japan's long-standing dermatopharmacokinetic (DPK)-centered framework. Unlike prior studies primarily surveying regulatory documents, this review provides an in-depth analysis of the scientific rationale behind the revised Japanese framework, including the repositioning of DPK studies and introduction of Q1/Q2/Q3-based evaluation principles. The revision builds on two decades of domestic experience accumulated through collaborations among regulatory authorities, dermatological experts, and academic researchers, reflecting a balanced evolution rather than the mere adoption of overseas trends. A range of BE evaluation methodologies, including clinical endpoint, pharmacodynamic (PD), DPK, and in vitro studies, are briefly outlined, highlighting their regulatory context and current trends. Special attention is given to the evolving role of in vitro testing and the mechanistic understanding of formulation attributes, which support a paradigm shift toward a more science-based, product-specific BE strategy. By comparing regulatory approaches across Japan, the European Union, and the United States, this review elucidates the key similarities and divergences, offering insights for future regulatory convergences. This science-driven reform in Japan is expected to enhance both the regulatory rigor and efficiency of pharmaceutical development, thereby supporting patient access to high-quality, affordable generic semi-solid topical dermatological drug products.

Accurate vital sign (VS) documentation is essential in clinical research to ensure participant safety and data integrity. However, protocol deviations related to VS transcription and documentation remain a persistent challenge. This quality improvement project aimed to reduce VS-related protocol deviations through the implementation of monitor integration (MI) technology on an inpatient clinical research unit at an urban academic medical center. Guided by Lewin's Change Management Model, the intervention included structured educational sessions for 31 clinical research nurses (CRNs), emphasizing protocol adherence, the use of MI to reduce documentation errors, and hands-on MI training. Peer support champions were designated to provide bedside guidance. A two-week audit compared VS-related protocol deviation rates from 451 pre-intervention and 682 post-intervention research visits. Following implementation, VS-related protocol deviations decreased significantly from 2.7% to 0.3% (p < 0.001). Nurse adoption of MI improved through targeted education and peer support, promoting alignment with Good Clinical Practice (GCP) guidelines and enhancing workflow efficiency. The combination of MI technology, training, and peer mentorship successfully reduced documentation errors and improved data quality. Despite initial resistance, CRNs adopted a new process, demonstrating the value of integrating technology into clinical workflows. Limitations include a short intervention period and the study's single institution setting. MI technology, when paired with education and peer support, can reduce VS-related protocol deviations and strengthen research compliance. These findings support broader adoption of MI in clinical research settings and underscore the importance of continued investment in CRN education and health technology integration.

Traditional manual MedDRA coding in clinical data management (CDM) faces persistent challenges, including suboptimal site data quality, terminology complexity, low efficiency, inconsistent outcomes, frequent dictionary updates, and regulatory timeliness pressures-all of which hinder trial progress and compliance. This study aimed to identify applicable artificial intelligence (AI) technologies for MedDRA coding, validate their performance in core CDM scenarios, and propose solutions for technical and regulatory hurdles. Conducted from January 2025 to April 2025, the study utilized real-world adverse event (AE) data from Hengrui Pharmaceutical's trials: 200 English/200 Chinese AE records (spelling error detection) and 2712 unique AE terms from a Phase II Chinese oncology trial (automated coding). A RAG-AI-Agent integrated framework was developed, incorporating integrated data processing (EDC-MedCoding integration), Large Language Models (LLMs; DeepSeek-R1/V3, Gemini 2.5 Pro, Grok3), Retrieval-Augmented Generation (RAG), and AI-Agent technologies. Performance was evaluated via Precision, Recall, coding time, and workload metrics. DeepSeek-V3 (task-optimized non-reasoning LLM) achieved 100% Precision in both languages for spelling detection; real-world validation yielded 85.1% Precision and ~ 70% manual review workload reduction. The automated coding system reduced average coding time by 48.7% (8.0 → 3.9min/record) with 95.8% coverage of AE terms, while maintaining 70%precision against manual gold standards. Compliance was ensured via local deployment and 21 CFR Part 11-aligned audit trails. The AI-enhanced framework significantly improves CDM efficiency, consistency, and compliance. Despite limitations (oncology-only validation, narrow language scope, synonym library dependence), it provides a replicable model for pharmaceutical digital transformation, accelerating drug development and enhancing patient safety through high-quality clinical data.

Incredible breakthroughs in scientific discoveries for the treatment of breast cancer have led to rapid improvements in health outcomes and quality of life for patients seeking healthcare solutions. However, the lack of inclusion of patients in clinical research who are disproportionately impacted by this devastating condition remains a significant challenge to researchers, healthcare institutions and communities alike. This report presents a framework for the inclusion of under-represented women, namely Black women, with breast cancer in clinical research. It also examines key factors influencing recruitment and retention, including patient perspectives. These insights can be applied across therapeutic areas to inform study design, enhance patient engagement, and improve population-based representation in clinical research.

The randomized controlled trial (RCT) is widely regarded as the gold standard in clinical development due to its ability to support robust statistical inference. In early-phase oncology development, however, trialists and statisticians may face obstacles such as small patient populations, which hinder the inclusion of a randomized control arm due to recruitment challenge and timeline urgency in drug development for these small populations. The issue is further exacerbated when drug development targets multiple similar but distinct patient populations, and meanwhile concurrent patients have prognoses that differ from those in previous trials within each patient population, upon which key design assumptions are based. Moreover, FDA's Project Optimus puts more emphasis to earlier dose optimization and the optimal dose may differ across treatment regimens and patient populations. To address this, we developed a platform trial design to support proof-of-concept (POC) decision-making in a randomized controlled trial (RCT) setting and dose optimization in alignment with FDA's Project Optimus. The method builds on the Multi-Arm Two-Stage (MATS) design (Jiang in Contemp Clin Trials 132:107278, 2023) by incorporating randomized control arms and inherits its feature of stopping futile drugs at the end of Stage 1, prior to further dose optimization in Stage 2. All are conducted within an RCT setting to enhance the robustness of decision making. To further utilize the patient resource in these small populations, we enable control borrowing across cohorts using the exchangeability-nonexchangeability (EXNEX) framework (Neuenschwander et al in Pharm Stat 15 (2):123-134, 2016), thereby improving statistical efficiency-an especially important consideration that the standard of care in these small populations may deliver similar efficacy outcome. We demonstrated how our method can promote efficient early oncology development in these small and similar patient populations through a case study.

Access to cross-border clinical trials may represent the sole therapeutic option for children living with rare diseases for which no approved medicines exist. Many children are excluded from participation in trials due to language restrictions. There are insufficient comprehensive analyses of the experiences and preferences of parents across Europe concerning participation and exclusion of their child in international clinical trials, particularly regarding language support during enrollment in cross-border clinical research studies. An anonymous online survey was designed and translated into 22 official European languages to collect data from parents of children living with a disease across Europe. The survey included five sections: (1) sociodemographic information; (2) experience participating in a clinical trial; (3) experience in cases where the patient was unable to take part in a study abroad; (4) experience participating in a clinical trial abroad; and (5) preferences regarding decentralized trial options. 1,436 responses were analyzed from parents across 34 European countries. 55.7% of the parents reported being able to communicate in English. 10.7% had prior clinical trial experience, of whom 30.1% traveled abroad to enable their child to participate. Among those reporting being excluded from cross-border trials, 34.7% cited language barriers or country of residence as the reason. Most families expressed a strong willingness to accept decentralized trial options, regardless of where the study may be conducted. Accommodating language translation to permit participation in a clinical trial abroad is feasible. While a significant percentage of caregivers of pediatric patients in Europe could communicate in English, approximately one-third of those excluded from clinical trials cited language barriers or country of residence as the reason. When translation was required, the most commonly offered solution was the use of professional interpreters, an accommodation that could enable broader patient participation in essential research.