Investigator-initiated Randomized Controlled Trials in Infectious Diseases: Better Value for Money for Registration Trials of New Antimicrobials.

Randomized controlled trials (RCTs) conducted by the industry are expensive, especially trials conducted for registration of new drugs for multidrug-resistant (MDR) bacteria. Lower-cost investigator-initiated trials have recently been successful in recruiting patients with severe infections caused by MDR bacteria. In this viewpoint, we contrast the aims, methods, and resulting costs of industry-led and investigator-initiated trials and ask whether contemporary registration trial costs are justified. Contract research organizations, delivering and monitoring industry-sponsored trials at a significant cost, have little incentive to make trials more efficient or less expensive. The value of universal monitoring of all trial data is questionable. We propose that clinical trial networks play a more influential role in RCT design and planning, lead adaptive risk-based trial monitoring, and work with the industry to maximize efficient recruitment and lower costs in registration trials for the approval of new antimicrobials.

[Drug assessment: IQWiG, G-BA, and an international comparison]. / Arzneimittelbewertung: IQWiG, G-BA und internationaler Vergleich.

BACKGROUND: Since the Pharmaceutical Market Restructuring Act (Arzneimittelmarktneuordnungsgesetz-AMNOG) went into effect on 1 January 2011, new medicinal products provided under statutory health insurance have to undergo an early benefit assessment, prepared on the basis of scientific dossiers drawn up by the German Institute for Quality and Cost Effectiveness in the Health Care Sector (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen-IQWiG) and adopted by the Federal Joint Committee (Gemeinsamer Bundesausschuss-G-BA). These assessments, in which the additional benefit of a product is compared with existing standard therapy and ultimately has a bearing on price negotiations with the pharmaceutical companies, are carried out on the basis of clinical trial data presented by the latter. Results so far, however, show that the IQWIG's and the G-BA's assessments often vary, although both bodies have the same documentation. Such differences can also be observed on an international level. OBJECTIVES: Using selected examples, the differences in the assessments of new pharmaceuticals are presented and reasons for national and international deviations are discussed. CURRENT DATA: As yet, no systematic comparative analysis has been made of assessments of medicinal products by the respective institutions. For this reason, it was not possible to make a systematic selection of pharmaceuticals, and the cases were instead selected according to available information. CONCLUSIONS: An overview of the results shows that the diverging assessments-both national and international-are not always scientifically justifiable, but rather appear to be influenced by the-not always transparent-framework parameters of the respective health system. Assessments are always shaped by certain perspectives on the data and results under scrutiny. It would undoubtedly be worthwhile to evaluate these influences to gain a better understanding of the reasons for national and international discrepancies in the assessment of additional therapeutic value of new pharmaceutical products.

Botanicals as "new" drugs: US development.

Botanicals are ingredients that can be marketed as foods, drugs, cosmetics, and medical devices in the United States. When a botanical is intended to diagnose, treat, prevent, mitigate, or cure a disease, it is considered to be a "drug". This article reviews the US regulatory requirements for botanicals as "new" drugs. An overview of the regulatory principles used to determine product category and the basic elements of an Investigational New Drug application and New Drug Application with the US Food and Drug Administration are presented. This article is part of a Special Issue entitled "Botanicals for Epilepsy".

Trends and Characteristics of New Drug Approvals in China, 2011-2021.

BACKGROUND: In the past decade, the Chinese drug regulatory system has undergone many changes. A major reform starting in 2015 has significantly reshaped the regulatory processes. It was important to assess the impact of the reform on new drug approvals in China. METHOD: We analyzed the temporal trends of regulatory characteristics of the new drugs approved by the Chinese regulatory agency from 2011 to 2021, using data collected in the Pharmcube database. RESULTS: A total of 353 new drugs were approved, including 220 small molecule drugs, 86 biological products and 47 vaccines. The annual number of new drug approvals increased dramatically since 2017, reaching a record high of 70 in 2021. The median NDA approval time was 15.4 months in 2017-2021, the shortest in the decade, and was significantly shorter than that in the pre-reform period. The newly instituted expedited pathways such as priority review (PR) and accelerated approval for urgently needed overseas drugs (UNOD) significantly reduced new drug application (NDA) approval times compared with standard review. For imported drugs, in 2017-2021, the median time difference between the first approval in the world and the approval in China was 5 years, representing significant "drug lag". However, the proportion of the imported drugs approved in China within 3 years of its first foreign approval has increased to 24.4% in 2017-2021. CONCLUSION: The regulatory reform has produced significant, positive immediate outcomes in several metrics of drug regulatory approval. China's regulatory system will continue to evolve as there still are many areas requiring further reform and improvement.

Appraisal of Novel Oncological Therapies by the Scottish Medicines Consortium and the National Institute for Health and Care Excellence: A Comparative Study of Six Years of Data.

Background and aims Pharmacoeconomic assessment of novel oncological therapies is an increasingly important factor in determining patient access to therapies. Organisations such as the National Institute for Health and Care Excellence (NICE) in England and the Scottish Medicines Consortium (SMC) in Scotland assess medications for their cost-effectiveness through health technology assessments (HTA) and provide guidance on whether the public health service should fund a therapy. We assessed six years of data to determine if there were any differences in timescales and decisions between NICE and SMC for new oncological therapies. Methods and results Time (days) from marketing authorisation (MA) to publication of final HTA guidance was calculated for single technology appraisals published by NICE and SMC between January 1, 2017, and December 31, 2022, for oncological therapies. We assessed 161 HTAs by NICE and 148 HTAs by SMC published in the study period. The median time from MA to publication of HTA guidance was 291 days (IQR 222-406) for SMC and 257 days (IQR 167-448) for NICE (p=0.054). For solid organ cancer therapies, NICE was significantly faster in publishing guidance, with a median of 231.5 days (IQR 148-392.25), compared to SMC, which took 273 days (IQR 202-378) (p=0.039). Overall recommendation of technologies was similar between the SMC and NICE (90.5% and 89.4%, respectively), with discordance in a minority of cases (12.6%). Conclusions Recommendation rates for single HTAs are similar between NICE and SMC for oncological therapies with discordance in a minority of cases. The time from MA to publication of HTA guidance was similar overall, but NICE was faster in publishing HTA guidance for solid organ cancer indications. Differences in methodology and process between the two organisations, in particular the presence of the Cancer Drugs Fund in England, may explain this difference in publication times.

Insights into the FDA 2018 New Drug Approvals.

OBJECTIVE: The Center of Drug Evaluation and Research (CDER) in the food and drug administration (FDA) approves new drugs every year. This review discusses the novel drugs of the FDA in 2018, with emphasis on the breakthrough drugs, the milestones in the approved list, and drugs with the highest expected sales in 2024. METHODS: The following scientific search engines were surveyed for the clinical trials of the drugs approved by the FDA in 2018: Pubmed, Springer link, ScienceDirect, Scopus, Wiley online library, Taylor and Francis, and Google Scholar. The total forecast sales were compared based on information from the Cortellis database, EvaluatePharma, and Nature Biobusiness Briefs. RESULTS: The 2018 year was full of good news for the drug market in the USA, with 59 new drug approvals by the FDA, which is the highest number of approvals in the last twenty years. The oncology and the antimicrobial drugs represent almost 50% of the new list, which gives hope to cancer patients and subjects with infectious diseases. In the 2018 FDA list, a number of drugs are expected to exceed 1$ billion dollars of sales by 2024. CONCLUSION: The new drugs approved by the FDA in 2018 have been reviewed. This year showed the highest number of new drug approvals in the last two decades. Among the 59 drugs approved in 2018, 14 drugs are considered breakthroughs, which revive hope for many poorly managed diseases. The list also contains 19 drugs that are first in class and 43 that were given priority reviews.

Regulation of New Drug Approval in Taiwan.

Taiwan Food and Drug Administration (TFDA) was established in 2010 as the nation's principal consumer product protection agency of food, drugs, medical devices, and cosmetics. By integrating 4 agencies (the Bureau of Food Safety, Bureau of Pharmaceutical Affairs, Bureau of Food and Drug Analysis, and Bureau of Controlled Drugs), TFDA holds the mission of protecting and promoting the public health through regulation modernization to enhance the availability of safe medical products and foods. To address the unmet medical needs and public health, TFDA has utilized regulatory science to evaluate review principles and risk management to properly oversee the overall life cycle of medicinal products. A lot of measures have been accomplished to build an efficient, transparent, and internationally harmonized regulatory system. With the first-in-the-world new drug afatinib approved in Taiwan, TFDA has successfully built up capacity and capability in the review and approval of new drugs. This article summarizes the efforts TFDA has been making in the domain of medicinal product management, highlighting policies and strategies for the future.