Phase IV Drug Trials With a Canadian Site: A Comparison of Industry-Funded and Non-Industry-Funded Trials.

Recent regulatory reforms have favored expedited drug marketing and increased reliance on Phase IV clinical trials for safety and efficacy assurance. This study, utilizing ClinicalTrials.gov, assesses the characteristics of Phase IV trials, with at least one site in Canada, examining those funded by industry sponsors and those lacking industry funding. Additionally, it compares the publication status of industry-funded and non-industry-funded trials through a manual review of the medical literature. Between 2000 and 2022, 864 Phase IV trials were completed, with 480 (55.6%) receiving industry funding and 384 (44.4%) funded solely by non-industry sources. Industry-funded clinical trials were larger (mean 204 enrollees versus 70), more likely to be international (57.7% versus 9.6%) and reported results more promptly (1.21 years after completion versus 1.85 years), yet both types shared similar designs, outcomes, and completion times. Publication rates were 81.8% for industry-funded and 65.8% for non-industry-funded trials. The ClinicalTrials. gov registry displayed 48 inaccuracies in publication associations, raising concerns about its accuracy. Our findings underscore the existing institutional limitations in ensuring comprehensive reporting and publication of Phase IV trial results funded by both industry and non-industry sources.

Evaluation of the strategies opioid manufacturers used to recruit health professionals and encourage overprescribing: an analysis of industry documents.

BACKGROUND: More than 263,000 individuals died due to prescription opioid misuse between 1999 and 2020. Between 2013 and 2015 alone, pharmaceutical companies spent over $39 million to market opioids to over 67,000 prescribers. However, there is still limited information about differences in provider responses to promotions for medications. In this study we investigated and evaluated strategies used by opioid manufacturers to encourage overprescribing, specifically focusing on oncology. METHODS: We conducted a retrospective review of opioid industry documents released in litigation between 1999 and 2021. We began with a preliminary search for business plans in a subset of collections that identified key terms and phrases. These search terms were then used to narrow the investigation, which ultimately focused on Insys Therapeutics, and how they targeted oncology providers as well as patients with cancer pain. RESULTS: We found that, overall, Insys sought to market to institutions with fewer resources, to less experienced and high-volume providers, and directly to cancer patients, with the goal of encouraging increased opioid prescribing and use. CONCLUSIONS: Our research revealed gaps in provider training that may make some providers more susceptible to pharmaceutical marketing. Developing and promoting continuing education courses for providers that are free from conflicts of interest, particularly at smaller institutions, may be one step towards reducing opioid overprescribing and its associated harms.

Ethical and Practical Considerations for an Agreement to Ensure Equitable Vaccine Access Comment on "More Pain, More Gain! The Delivery of COVID-19 Vaccines and the Pharmaceutical Industry's Role in Widening the Access Gap".

This paper discusses the potential of an international agreement to ensure equitable vaccine distribution, addressing the failures witnessed during the COVID-19 pandemic. COVAX was unable to prevent vaccine monopolization and unequal distribution, which led to significant disparities in vaccination rates and avoidable deaths. Any future agreement on equitable vaccine distribution must address ethical and practical issues to ensure global health equity and access. The proposed agreement should recognize healthcare as a human right and consider vaccines beyond mere commodities, emphasizing the social responsibility of pharmaceutical companies to prioritize affordability, availability, and accessibility, particularly for low-income countries (LICs). Voluntary licensing agreements are suggested as a means to enhance access to essential medicines. The paper also outlines the necessity of international cooperation, with robust compliance mechanisms, to effectively enforce such an agreement and mitigate future health crises.

Profits First, Health Second: The Pharmaceutical Industry and the Global South Comment on "More Pain, More Gain! The Delivery of COVID-19 Vaccines and the Pharmaceutical Industry's Role in Widening the Access Gap".

The pharmaceutical industry has a long history of prioritizing the research and sale of medicines that will yield the largest amount of revenue and placing the health of people second. This gap is especially prevalent in countries of the Global South. This article first explores the dichotomy in research between the Global North and the Global South and then looks at examples of how access to key medicines used in diseases such as HIV, oncology and hepatitis C is limited in the latter group of countries. The role of pharmaceutical companies during the COVID-19 pandemic prompted negotiations for a pandemic accord that would ensure more equity in both research and access when the next pandemic comes. However, efforts by a combination of the pharmaceutical industry and some high-income countries (HICs) are creating serious obstacles to achieving the goal of an accord that would place health over profits.

Non-research payments to board-certified cardiologists from pharmaceutical industry in Japan from 2016 to 2019: a retrospective analysis.

OBJECTIVES: To evaluate the extent and trends of personal payments from pharmaceutical companies to cardiologists board-certified by the Japanese Circulation Society. DESIGN: A retrospective analysis study using data from a publicly available database. SETTING: The study focused on payments to cardiologists in Japan. PARTICIPANTS: All 15 048 cardiologists who were board-certified by the Japanese Circulation Society as of 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the extent of personal payments to cardiologists in 2016-19. Secondary outcomes included the analysis of trends in these payments over the same period. RESULTS: Of all 15 048 board-certified cardiologists, 9858 (65.5%) received personal payments totaling $112 934 503 entailing 165 013 transactions in 2016-19. The median payment per cardiologist was $2947 (IQR, $1022-$8787), with a mean of $11 456 (SD, $35 876). The Gini Index was 0.840, indicating a high concentration of payments to a small number of cardiologists. The top 1%, 5% and 10% of cardiologists received 31.6%, 59.4% and 73.5% of all payments, respectively. There were no significant trends in the number of cardiologists receiving payments or number of payments per cardiologist during the study period. CONCLUSIONS: More than 65% of Japanese cardiologists received personal payments from pharmaceutical companies over the 4-year study period. Although the payment amount was relatively small for the majority of cardiologists, a small number of cardiologists received the vast majority of the payments.

Assessing the impact of the Physician Payments Sunshine Act on pharmaceutical companies' payments to physicians.

Enacted in 2010 as part of the Affordable Care Act, the Physician Payments Sunshine Act (PPSA) mandates transparency in financial interactions between pharmaceutical companies and healthcare providers. This study investigates the PPSA's effectiveness and its impact on industry payments to physicians. Utilizing ProPublica and Open Payments databases, a difference-in-difference analysis was conducted across ten states. Results reveal a significant reduction in pharmaceutical companies' meal-related payments post-PPSA, impacting both the total payment amount and the number of unique physicians reached. Conversely, travel payments showed no significant impact in the primary analysis. However, subsequent analyses revealed nuanced reductions in the number of unique physicians reached, highlighting a more intricate relationship wherein pharmaceutical companies likely adjusted their financial interaction strategies with physicians differently across states. State-level variations in meals further underscore the complexity of PPSA's influence. This pioneering research contributes valuable empirical evidence, addressing gaps in prior studies and emphasizing the ongoing need for policy assessment to guide industry-physician relationships.

How Can General Managers Best Leverage Medical Affairs Now and in the Future?

General managers (GMs) play a crucial role as enterprise leaders of the country affiliate of multi-national pharmaceutical companies, balancing needs, objectives and governance across all local functions. One such function, Medical Affairs, has undergone a significant evolution from a support function into a strategic partner and in some organizations a strategic leader supported by the increasing complexity of medications and a shift to more specialized medicines. Although the function has progressed significantly, there is opportunity to elevate Medical Affairs to another level, with GMs and business unit directors (BUDs) recommending increased business acumen, strategic approach, innovation and project management as competencies that could be further cultivated. Examining the current trends in the industry, including the increasing complexity of innovative medicines and patient journeys, a higher burden of evidence for the reimbursement of medicines, innovative data generation opportunities, the changing stakeholder engagement expectations and the focus on corporate reputation, Medical Affairs is positioned as a key to assist in navigating the organization through these complexities. The GM can help to foster the evolving role of Medical Affairs, encouraging lateral moves for broader enterprise mindset, imparting a culture of shared governance responsibilities across functions to encourage innovative thinking and nurture upcoming leaders by investing in training to take advantage of the above trends and deliver best patient and organizational outcomes now and in the future.

Drug supply and assurance: a cross-sectional study of drug shortage monitoring varieties in China.

BACKGROUND: Drug shortage is a worldwide problem that seriously threatens public health. China released the most comprehensive list of key drug shortage monitoring varieties ever in 2022. We aim to analyze the attributes and characteristics of the medicines within the list to provide a reference for improving China's supply security of shortage drugs. METHODS: We used public data to extract information on drug types, dosage forms, indications, classification of clinical uses, whether they were included in medical catalogs such as the National Essential Drugs, and the number of drug and active pharmaceutical ingredient (API) manufacturers. A descriptive statistical analysis was used. RESULTS: Of the 980 drugs on the list, 99.59% were chemicals and 92.65% were injectables. Drugs for blood and hematopoietic organs, the cardiovascular system, and the digestive tract and metabolism ranked among the top three shortages. Verification of the medical catalogs showed that 90.41% of the drugs belonged to the national essential drugs, 95.10% were medicare drugs, 2.55% were volume-based procurement drugs, and 14.70% were for rare diseases, and 42.04% were for children. In terms of drug supply capacity, 21.33% of drug approvals are less than 10, and there were even 26 drugs for exclusive production, close to 90% of manufacturers need to purchase APIs from outside. Among the 256 APIs included in the list, 152 APIs had less than 10 manufacturers, and there were even 5 APIs produced by only one enterprise nationwide. CONCLUSIONS: The situation of drug shortages in China was severe and complex, with serious shortages of medicines adapted to basic medical and healthcare needs and clinically necessary medicines, and a need to improve the production capacity of drugs and the ability to supply APIs. We recommend strengthening drug monitoring and stockpiling and accelerating the approval of shortage drugs to improve drug supply security.

An Insight Into Risk Assessment and Reformulation of Drug Products Manufactured Using Benzene Grade Carbomer: A Regulatory Perspective.

Cancer has been an enormous pain point for patients and regulatory bodies across the globe. In Dec. 2023, the US FDA released guidance on benzene-grade carbomer formulations, which triggered pharmaceutical manufacturers to assess risk, test finished products, and reformulate drug products with benzene-grade carbomer. The immediate implementation of the stoppage of finished products with benzene-grade carbomers has threatened pharmaceutical excipients and finished product manufacturers. The gravity of this situation prompted the US Pharmacopeia to extend the deadline for discontinuation from August 1, 2025, to August 1, 2026, allowing manufacturers ample time for reformulation and regulatory compliance.There is an immediate need to understand the guidance and to learn how manufacturers should do the risk assessment and approach reformulation. This review provides an in-depth analysis of the risk assessment and reformulation processes involved in various dosage forms utilizing benzene-grade carbomer, supported by specific case studies.This review offers insights into navigating the USFDA guidelines to ensure formulation safety and compliance, thus enabling pharmaceutical practitioners to uphold the highest standards of patient care and tackle life cycle management challenges.The decision of the USFDA to restrict the usage of high benzene content of carbomer in the formulation is a welcome move. This article has shown a way for researchers to see opportunities in the path and provide best-in-class medicines to patients with a better formulation safety profile.

Leveraging AI and Machine Learning in Six-Sigma Documentation for Pharmaceutical Quality Assurance.

The pharmaceutical industry must maintain stringent quality assurance standards to ensure product safety and regulatory compliance. A key component of the well-known Six Sigma methodology for process improvement and quality control is precise and comprehensive documentation. However, there are a number of significant issues with traditional documentation procedures, including as slowness, human error, and difficulties with regulatory standards. This review research looks at innovative ways to employ machine learning (ML) and artificial intelligence (AI) to enhance Six Sigma documentation processes in the pharmaceutical sector. AI and ML provide cutting-edge technologies that have the potential to drastically alter documentation processes by automating data entry, collection, and analysis. Natural language processing (NLP) and computer vision technologies have the potential to significantly reduce human error rates and increase the efficacy of documentation processes. By applying machine learning algorithms to support real-time data analysis, predictive analytics, and proactive quality management, pharmaceutical organizations may be able to identify potential quality issues early on and take proactive efforts to address them. Combining AI and ML improves documentation accuracy and reliability while also strengthening compliance with stringent regulatory criteria. The primary barriers and limitations to the current state of Six Sigma documentation in the pharmaceutical industry are identified in this study. It examines the fundamentals of AI and ML with an emphasis on their specific applications in quality assurance and potential benefits for Six Sigma processes. The report includes extensive case studies that highlight notable developments and explain how AI/ML enhanced documentation is used in the real world.

Measuring and Understanding Market Exclusivity Length for New Prescription Drugs in France, Australia, and the USA.

BACKGROUND: Originator drug manufacturers use several strategies to delay generic competition in the USA, but it remains unclear whether this results in longer market exclusivity compared to other countries. OBJECTIVES: We sought to understand how drug market exclusivity lengths vary between the USA and two comparable countries. METHODS: We focused on drugs approved within 2 years of each other in the USA, France, and Australia from 1995 to 2005, and we compared the lengths of exclusivity from marketing approval through first generic competition or June 2023 using Kaplan-Meier analyses. RESULTS: Among 165 drugs in common between the USA and France, the median length of exclusivity was slightly longer in France (15.0 years, interquartile range [IQR]: 13.0-19.6) than the USA (14.5 years, IQR: 11.7-17.6). Among 100 drugs in common between the USA and Australia, the median length of exclusivity was longer in Australia (16.3 years, IQR: 13.9-22.4) than in the USA (14.4 years, IQR: 12.0-17.1). CONCLUSIONS: Market exclusivity lengths in the USA are not longer than in France and Australia. Potential reasons include the larger US market and incentives that offer transient high generic drug prices in the USA for manufacturers that successfully challenge originator market exclusivity.

Statistical Signal Detection Algorithm in Safety Data: A Proprietary Method Compared to Industry Standard Methods.

INTRODUCTION: Several quantitative methods have been established, in pharmacovigilance, to detect signals of disproportionate reporting (SDRs) from databases containing reports of adverse drug reactions (ADRs). The signal detection algorithms (SDAs) and the source of the reporting per product vary, but it is unclear whether any algorithm can provide satisfactory performance using data with such large variance factors. OBJECTIVE: Determine the appropriate SDA for Biogen's internal Global Safety Database (GSD) given the characteristics of the database including frequencies of events, data skewness, outliers, and missing information. Compare performance of standard approaches (EBGM, EB05, PRR, and ROR), well accepted by industry, to a Biogen-developed Machine Learning (ML) Regression Decision Tree (RDT) model, across several Biogen products, to determine a champion SDA. METHODS: All data associated with seven marketed Biogen products were chosen and a historical subset of reported ADRs were considered. Six SDAs (five common industry disproportionality methods) and RDT were evaluated. The SDRs were calculated on training and test data composed of quarterly reporting intervals from 2004-2019. The performance measures used were sensitivity, precision, time to detect new events, and frequency of detected cases for each algorithm for each product. Outcomes in the test data are known a priori and easily compared to predicted outcomes. Validation was performed via rates of misclassification. This work solely represents Biogen's internal information, intentionally chosen to serve the performance review of its signal detection systems, and results will not necessarily be generalizable to other external sources. RESULTS: Several algorithms performed differently among products, but no one method dominated any other. Performance was dependent on the thresholds used to define a signal according to different criteria. However, those different statistics subtly influenced the achievable performance. The relative performance of RDT and Medicines and Healthcare products Regulatory Agency (MHRA) algorithms were superior and paired across products. A reduction in precision for all methods spanning the products was present. Hence, companies evaluating signal detection approaches, search for innovative methods to minimize this effect. CONCLUSIONS: In designing signal detection systems, careful consideration should be given to the criteria that are used to define SDRs. The choice of disproportionality statistics does not affect the achievable range of signal detection performance. These choices should consider mainly ease of implementation and interpretation. The implementation of a method is specific to its accuracy. The RDT attempted to take advantage of known methods and compare results on a per-product basis. Many factors influencing ADRs may improve RDT in future efforts. In this experiment, RDT demonstrated superiority in terms of quickest time to detect and capturing of the highest number of ADRs. Next steps include expansion of data for products representing other indications and testing models in external databases to investigate generalizability of estimates when comparing SDAs.