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BACKGROUND AND OBJECTIVES: Adult cancer drugs have historically been exempted from pediatric testing requirements. In 2017, Congress passed the Research to Accelerate Cures and Equity (RACE) for Children Act to expand mandatory pediatric testing to cancer drugs; the law took effect in 2020. With this study, we sought to evaluate how the pediatric testing of molecularly targeted adult cancer drugs changed after the RACE Act. METHODS: In this retrospective cohort study, we used publicly available Food and Drug Administration data to compare pediatric post-approval requirements, trials, and trial characteristics, including timing, in adult cancer drugs before and after the RACE Act. RESULTS: Between 2017 and 2024, the Food and Drug Administration approved 61 adult cancer drugs with molecular targets relevant to pediatric cancer; 40 were submitted before 2020, and 21 were submitted after 2020. The 40 pre-RACE Act drugs were associated with no pediatric post-approval requirements, whereas the 21 post-RACE Act drugs were associated with 15 pediatric post-approval testing requirements. Approximately two-thirds (26/40, 65%) of pre-RACE Act drugs and 57% (12/21) of post-RACE Act drugs were evaluated in pediatric trials. Among pre-RACE Act cancer drugs, pediatric trials were initiated a median of 0.04 years after approval (interquartile range: -3.3 to 1.9 years), whereas post-RACE Act trials were initiated a median of 2.8 years before approval (interquartile range: -4.3 to 0.3 years). CONCLUSIONS: The RACE Act has been associated with greater numbers of pediatric postapproval testing requirements and the earlier initiation of pediatric trials, although early pediatric trial rates appear unchanged. Formalizing pediatric testing requirements may lead to the timely completion of pediatric studies to the benefit of pediatric patients with cancer. [ABSTRACT FROM AUTHOR]

The text explores the use of algorithms by federal agencies in administrative processes, emphasizing the importance of policies and procedures in guiding decision-making. It discusses the potential for bias in datasets used to train algorithms and the need for transparency in bias mitigation strategies to build trust in algorithmic results. The author proposes a normative framework to evaluate algorithms based on systemic reasons, intended recipients, decision nature, and bureaucratic considerations, suggesting that algorithms used for agency action should disclose systemic reasons to survive review. The article aims to reconcile the use of algorithms with administrative law's reason-giving requirements and highlights the challenges and implications of using algorithms as reasons for agency action. [Extracted from the article]

Background: Although a variety of drug delivery devices have been launched in recent years, few studies have comprehensively investigated the market trends of combination drugs and medical devices approved or certified in Japan and the regulatory challenges related to their approval. Among the drug delivery devices, autoinjectors are more convenient than traditional prefilled syringes and are designed with safety features to prevent needlestick accidents, allowing self-injection by patients. Therefore, autoinjectors have been incorporated into the treatment of various diseases and have shown significant growth among drug delivery devices. Aim: This study aimed to investigate the market trends of combination drugs approved in Japan, especially those with autoinjector formulations, and to explore the challenges in the regulatory aspects of combination drugs. Methods: Information on the number of marketed drugs and medical devices was obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) database using specific definitions. We looked at the annual changes in the number of drug delivery devices approved and certified as combination drugs or medical devices and the number of canceled certifications. We also examined the classification and main certification criteria for Japanese medical device nomenclature. Results: The study suggested that the number of combination drugs with autoinjector formulations is increasing, replacing previously approved or certified pen-type medication injectors. Moreover, 53% of all drug products were approved for autoinjector formulations after the initial authorization approval in Japan, and more than half of them obtained approval for additional formulations for autoinjectors within five years of the initial authorization approval, with the largest number of cases obtaining approval for additional formulations two years later. Conclusion: The lack of clear regulatory requirements for autoinjectors may lead to confusion among applicants. Furthermore, there are challenges in filing regulatory applications, thus hindering the rapid launch of combination drugutilizing devices with superior usability. [ABSTRACT FROM AUTHOR]

The United States (U.S.) Food and Drug Administration (FDA) oversees the safety and quality of drugs and vaccines that are used in the U.S. Administration of the FDA falls under the jurisdiction of the U.S. Department of Health and Human Services (HHS). The regulatory oversight of the FDA is complex and comprehensive, requiring the various roles and responsibilities to be divided across six main centers. The activities of two of these centers, the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) are the primary focus of this review. [ABSTRACT FROM AUTHOR]

The article addresses concerns about the legality and safety of drug importation into the U.S., particularly for cancer care and employer health benefit plans. It highlights the ethical and legal responsibilities of medical practices and employers in ensuring drug safety and compliance with U.S. Food and Drug Administration (FDA) standards.

The US has found it hard to establish competition in the market for biologics, which are therapeutics derived from living cells. In the case of small-molecule drugs, the emergence of direct competition from generic drugs at the end of the exclusivity period has provided the impetus for price competition, leading to lower spending. In 2010, to spur competition in the biologics market, Congress created a simplified pathway for the US Food and Drug Administration (FDA) to approve comparable versions of biologic drugs called biosimilars. Biosimilar competition in the US has nonetheless remained weaker than in European peer countries. For example, as of August 2020, there were 52 biosimilars available in Germany, and only 15 in the US.1 An important contributor to this "biosimilar gap" has been the fact that biosimilars to biologic blockbusters such as adalimumab (Humira) and etanercept (Enbrel) were only (or will only become) commercially available in the US several years after receiving FDA approval, while they were available in Europe years earlier.2 Through the end of 2021, it took biosimilars a median of 301 days between receiving FDA approval and becoming available for use.3 In one recent study, the median length of time between when a biologic drug was approved and when its first biosimilar was made available to US patients was 21.5 years.4 This paucity of competition has contributed to high US spending on biologics. According to the Department of Health and Human Services, in 2022 41% of US drug expenditures was spent on biologics, which represented 16% of US prescriptions.5 [ABSTRACT FROM AUTHOR]

Over recent years, dozens of legal challenges have been instituted in response to government action during the COVID-19 pandemic. While public health orders have been challenged on several grounds, few cases have succeeded. Fewer cases still have called into question decisions made by the Therapeutic Goods Administration (TGA) to approve the COVID-19 vaccines. This section provides a brief update on one recent, partially successful COVID-19 health directions case before examining two applications in the Federal Court of Australia seeking judicial review of the TGA's approval of the COVID-19 vaccines. The section argues that, while both TGA applications were dismissed for lack of standing, they illustrate how and why third parties will ordinarily not be entitled to challenge administrative decisions about therapeutic goods. [ABSTRACT FROM AUTHOR]

The current regulatory path for new drug registration in East Asian countries has led to significant delay of the new medicines in these countries. A unified regulatory path and allowance of mutual usage of clinical data in East Asian countries would lead to cost saving in drug development and expedite the new drug registration in these countries. The objectives of the present analysis are to compare the approval dates of a selection of products developed by Pfizer in the United States and East Asian countries (China, Japan, Korea) and compare the pharmacokinetics and recommended doses of these products in East Asian countries. Eighteen products (20 drugs, 2 products with 2 combination drugs) with exposure data available in at least 2 of the 3 East Asian countries across different therapeutic areas were included in the analyses. The results showed that most products had delayed approval in East Asian countries (up to 8 years) after US or EU approval. No distinct differences were observed in the drug exposure and recommended doses for the selected products in East Asian countries. These results together with literature data of genetic similarity of the East Asian populations support the mutual usage of the clinical data in the East Asian countries for expedited regulatory submission and approval. [ABSTRACT FROM AUTHOR]

The article explores the concept of innovator liability, which holds branded drug manufacturers accountable for injuries caused by generic drugs. While some courts have recognized this theory, many have rejected it, citing concerns about the potential for unlimited liability and the responsibility of brand manufacturers for the actions of their competitors. The article discusses two Supreme Court cases that address preemption in state tort law claims against pharmaceutical manufacturers, with one case ruling in favor of state law claims against brand-name drug manufacturers and the other ruling in favor of preemption for generic drug manufacturers. The article also mentions a pending Restatement from the American Law Institute that may provide new inspiration for advocates of innovator liability. However, the article argues that courts should continue to reject innovator liability claims, as they could have negative consequences for the pharmaceutical industry. [Extracted from the article]

Policy PointsThe increasing number of drugs granted accelerated approval by the Food and Drug Administration (FDA) has challenged the Medicare program, which often pays for expensive therapies despite substantial uncertainty about benefits and risks to Medicare beneficiaries.We recommend several administrative and legislative approaches for improving FDA–Centers for Medicare and Medicaid Services (CMS) coordination around accelerated‐approval drugs, including promoting earlier discussions among the FDA, the CMS, and drug companies; strengthening Medicare's coverage with evidence development program; linking Medicare payment to evidence generation milestones; and ensuring that the CMS has adequate staffing and resources to evaluate new therapies.These activities can help improve the integrity; transparency; and efficiency of approval, coverage, and payment processes for drugs granted accelerated approval. Context: The Food and Drug Administration (FDA)'s accelerated‐approval pathway expedites patient access to promising treatments. However, increasing use of this pathway has challenged the Medicare program, which often pays for expensive therapies despite substantial uncertainty about benefits and risks to Medicare beneficiaries. We examined approaches to improve coordination between the FDA and Centers for Medicare and Medicaid Services (CMS) for drugs granted accelerated approval. Methods: We argue that policymakers have focused on expedited pathways at the FDA without sufficient attention to complementary policies at the CMS. Although differences between the FDA and CMS decisions are to be expected given the agencies' different missions and statutory obligations, procedural improvements can ensure that Medicare beneficiaries have timely access to novel therapies that are likely to improve health outcomes. To inform policy options and recommendations, we conducted semistructured interviews with stakeholders to capture diverse perspectives on the topic. Findings: We recommend ten areas for consideration: clarifying the FDA's evidentiary standards; strengthening FDA authorities; promoting earlier discussions among the FDA, the CMS, and drug companies; improving Medicare's coverage with evidence development program; tying Medicare payment for accelerated‐approval drugs to evidence generation milestones; issuing CMS guidance on real‐world evidence; clarifying Medicare's "reasonable and necessary" criteria; adopting lessons from international regulatory‐reimbursement harmonization efforts; ensuring that the CMS has adequate staffing and expertise; and emphasizing equity. Conclusions: Better coordination between the FDA and CMS could improve the transparency and predictability of drug approval and coverage around accelerated‐approval drugs, with important implications for patient outcomes, health spending, and evidence generation processes. Improved coordination will require reforms at both the FDA and CMS, with special attention to honoring the agencies' distinct authorities. It will require administrative and legislative actions, new resources, and strong leadership at both agencies. [ABSTRACT FROM AUTHOR]

The seriousness of the COVID-19 pandemic requires a look into the implementation of drug registration rules for COVID-19 vaccines. Amidst the surrounding exigencies, vaccines being a biological product, require comprehensive and continuing pre and post registration rules to ensure their safety and efficacy. The study focuses on Malaysia which has rules on drug registration that have been successfully applied to vaccines. The study shows that the rules have been tailor-made to emergency situations. At the moment, special rules have been introduced including to allow use of COVID-19 vaccines as unregistered product. Recognition of COVID-19 Vaccines Global Access (COVAX) facility and requirement for government sale only, are among the safety valves. The study shows that these however are temporary measures against the backdrops of possible entry of private players in the vaccination process. Therefore, regulatory responses to intellectual property (IP) related conditions underlying drug registration, and measures to ensure risk management involved in vaccine production, approval and administration are needed in the progressive rules pending further development of research in the area. [ABSTRACT FROM AUTHOR]

The prevalence of heart failure (HF) continues to rise in developed nations. Symptomatic congestion is the most common reason for patients to seek medical attention, and management often requires intravenous (IV) diuretic administration in the hospital setting. Typically, the number of admissions increases as the disease progresses, not only impacting patient survival and quality of life but also driving up healthcare expenditures. pH-neutral furosemide delivered subcutaneously using a proprietary, single-use infusor system (Furoscix) has a tremendous potential to transition in-hospital decongestive therapy to the outpatient setting or to the patient's home. This review is aimed at providing an overview of the pharmacodynamic and pharmacokinetic profile of the novel pH-neutral furosemide in addition to the most recent clinical trials demonstrating its benefit when used in the home setting. Given the newest data and approval by the Food and Drug Administration in the US, it has the potential to revolutionize the care of patients with decompensated HF. Undoubtedly, it will lead to improved quality of life as well as significantly reduced healthcare costs related to hospital admissions. [ABSTRACT FROM AUTHOR]

The article explores the 25th anniversary of HIPAA and its Privacy Rule, discussing two competing visions of data privacy and the ethical challenges posed by AI-enabled healthcare. It criticizes the Privacy Rule for not aligning with control-over-information theory and allowing for unconsented data disclosures. The article highlights the importance of inclusive and representative training data for AI/ML algorithms and raises concerns about bias and inequity in AI/ML Clinical Decision Support tools. It suggests the use of Privacy by Design techniques and proposes legal pathways to access diverse and inclusive data for AI/ML research. The article concludes by discussing the limitations of the HIPAA Privacy Rule and proposing measures to achieve state-of-the-art privacy protection in medical AI. [Extracted from the article]

Anti–vascular endothelial growth factor (VEGF) medications for intraocular use are a major and increasing cost, and biosimilars may be a means of reducing the high cost of many biologic medications. However, a bevacizumab biosimilar, which is currently pending Food and Drug Administration (FDA) approval (bevacizumab-vikg), paradoxically may increase the cost burden of intravitreal anti-VEGF agents, because off-label repackaged drugs may no longer be allowed per the Drug Quality and Security Act (DQSA). We aimed to investigate the potential impact of biosimilars on costs in the United States. Cost analysis of anti-VEGF medications. Medicare data from October 2022 and previously published market share data from 2019. Average sales prices (ASPs) of ranibizumab, aflibercept, and bevacizumab were calculated from Medicare allowable payments. The ASPs of biosimilars were calculated from wholesale acquisition costs from a representative distributor. The cost of an intraocular bevacizumab formulation is modeled at $500/1.25-mg dose and $900/1.25-mg dose. Costs of anti-VEGF drugs to Medicare Part B and patients. If an intraocular bevacizumab biosimilar were to be priced at $500, costs to Medicare would increase by $457 million from $3.01 billion to $3.47 billion (15.2% increase). Patient responsibility would increase by $117 million from $768 million to $884 million. Similarly, if intraocular bevacizumab were priced at $900, Medicare costs would increase by $897 million to $3.91 billion (29.8% increase), and patient responsibility would increase by $229 million to $997 million. If bevacizumab were $500/dose, switching all patients currently receiving ranibizumab or aflibercept to respective biosimilars would compensate for only 28.8% of the increased cost. Current prices of ranibizumab and aflibercept biosimilars would have to decrease by an aggregate of 15.7% to $616.80/injection, $1027.97/injection, and $1436.88/injection for ranibizumab 0.3 mg, ranibizumab 0.5 mg, and aflibercept, respectively. An FDA-approved bevacizumab biosimilar for ophthalmic use could increase costs to the health care system and patients, raising concerns for access. This increase would not be offset by ranibizumab and aflibercept biosimilar use at current prices. These data support the need for an exemption of section 503B of the DQSA and continued use of repackaged off-label bevacizumab. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

An introduction to a special section on the talks on gaps in older adult enrollment in clinical trials, new therapies' need for trial information, and the push to increase trial participation of older adults is presented.

The article explores the Hatch-Waxman Act, which is a series of amendments to the Federal Food, Drug and Cosmetic Act allowing for generic drug manufacturers to begin the approval process with the Food and Drug Administration for their generic drug, and its proposed expansion to regulate the healthcare products industry in the U.S. It discusses the need for a new, more expansive generics system. It describes obstacles faced in attempting to implement reforms in the medical devices field.

The article reports that access to the safe and effective abortion drug mifepristone is in jeopardy in the United States due to ongoing legal challenges by anti-abortion organizations, including a lawsuit filed by the Alliance for Hippocratic Medicine against the Food and Drug Administration. It notes that there is concern among researchers and reproductive rights advocates that legal attacks on abortion and contraception access will continue in the United States.

The article reports that the American College of Clinical Pharmacology recommends that researchers and health care professionals across the care continuum be more active in regard to the need for a greater diversity of participants in drug development and clinical trials. Topics include examines this can be supported through active participation in their professional and academic institutions, societies and local communities.

After receiving FDA approval, a generic drug manufacturer can launch ‘at risk’ before any patent infringement litigation concludes, but it risks paying damages if it ultimately loses the litigation. A generic can eliminate the risk by waiting to launch until after the appeals process is complete but waiting has downsides too. We examine FDA approvals of generic drug applications with ‘first-filer’ status (which precludes other generics from entering beforehand) to examine empirical patterns of at-risk entry. In our data, litigants usually settled prior to a legal decision. For the remainder, drugs that received FDA approval prior to a favorable district court decision were always launched at risk. Generics without FDA approval before a favorable district court decision launched upon approval unless the approval was close in time to the appeal decision, or it had forfeited the first-filer exclusivity (indicating a low cost of waiting). [ABSTRACT FROM AUTHOR]

(1) Background: A biosimilar is a biologic medical product that has been approved by the United States Food and Federal Drug Administration (FDA) and is an almost identical copy of an original biologic product yet manufactured by a different company. Biosimilars are often assumed to be the same as generic medications, while often made from living organisms. Through clinical trials, biosimilars have been shown to be both as safe and as effective as their originator products. Biosimilars have also proven they can reduce the costs to both insurance companies and patients in many circumstances. However, despite their cost savings, biosimilar manufacturers continue to face barriers in having oncologists and cancer centers prescribe them for their patients. This review aims to identify barriers associated with medical provider prescriptive behaviors related to biosimilars for patients. (2) Methods: Reviewers analyzed 27 articles and identified common themes. (3) Results: After a thorough literature review, the researchers identified seven barriers to prescribing of biosimilars: physician comfort in originators instead of biosimilars, patient reluctance to switch from a current biologic to a biosimilar, provider profits associated with an originator biologic, lack of stakeholder education on biosimilars, lack of provider team knowledge of biosimilars, lack of knowledge surrounding the biosimilar FDA approval process, and hesitancy to stock multiple drugs for a specific indication. (4) Conclusions: This review's findings of identified barriers to use of biosimilars provides insight for healthcare providers and organizations surrounding prescribing practices and potential treatment benefits for cancer patients who may benefit from biosimilar treatment medications. [ABSTRACT FROM AUTHOR]

Efgartigimod represents a first‐in‐class immunomodulatory agent that is comparable to TPE in reducing immunoglobulin levels. This translates to reductions in Myasthenia Gravis symptom scores with maximal effect following the fourth weekly efgartigimod dose. Efgartigimod received FDA approval in December of 2021 and may be an alternative particularly for patients on long‐term TPE regimens of weekly or less frequent. Apheresis practitioners, especially those managing long‐term apheresis in seropositive individuals, may therefore see some of their patients transitioned from plasma exchange to efgartigimod. Long‐term experience with efgartigimod remains lacking and studies are needed to establish the role of efgartigimod in the acute setting. [ABSTRACT FROM AUTHOR]

Background: Biosimilars account for 30–40% of biologic medications dispensed in the United States (US), yet healthcare providers in relevant medical specialties have limited awareness of biosimilars and their characteristics. Likewise, many providers perceive biosimilars as less safe and effective than original biologics and are more comfortable prescribing original biologics to patients. Methods: We conducted in-person focus groups at three clinical sites in California and Texas (n = 49) to explore the reasons behind US healthcare providers' limited understanding of, cautious attitudes toward, and reluctance to prescribe biosimilars. We conducted thematic analysis by having three researchers independently analyze verbatim transcripts and identify patterns in provider responses. Results: Providers' limited knowledge of and cautious attitudes toward biosimilars are driven by uncertainty about how biosimilarity is defined and operationalized as well as negative past experiences with generic drugs that did not perform as well as branded counterparts. Additionally, healthcare providers are unfamiliar with the Food and Drug Administration's (FDA's) approval pathway for biosimilars and are skeptical that an abbreviated approval process is rigorous enough to ensure biosimilars deliver the same efficacy and have the same side effect profiles as original biologics. Physicians also expressed concerns about pharmacy substitution of biosimilars and interchangeables, explaining they would be unaware of which medication was ultimately given to their patients. Conclusions: Educating physicians and pharmacists about biosimilars—including how biosimilarity is defined and operationalized, the structure of the biosimilar approval process, and how analytical data can ensure biosimilar safety and efficacy—will be important for reducing healthcare providers' concerns and increasing biosimilar adoption in the US. [ABSTRACT FROM AUTHOR]

The article reports on the need for the U.S. Food and Drug Administration (FDA) to reexamine the risk evaluation and mitigation strategy (REMS) for the pharmaceutical industry. Topics mentioned include some suggestions on how FDA can improve REMS program to improve patient safety, a case that highlights the importance of standardizing REMS processes, and the purpose of REMS to reduce the severity of a medication-related event.

The modern regime for balancing innovation and competition in pharmaceuticals was established through the Drug Price Competition and Patent Term Restoration Act of 1984, also known as the Hatch-Waxman Act. This regime needs updating. The process that Hatch-Waxman established for listing patents and challenging patents on the Food and Drug Administration's Orange Book is one important area for reform. [ABSTRACT FROM AUTHOR]

The article focuses on the MODERN Labeling Act in the US, which aims to facilitate the repurposing of drugs by updating generic drug labels with new medical uses. Topics include background and operation of the Act, highlighting its innovative approach of Food and Drug Administration's order label updates; and the European Union should adopt a similar policy as part of its Pharmaceutical Strategy, aligning with its goals of affordable medicines, sustainable innovation, and crisis preparedness.

A new class of drugs called biologics has potential to finally cure previously untreatable conditions such as cancer and Alzheimer's disease. But there is a catch: these innovative drugs are expensive. On average, prices range from $10,000 to $30,000 per year, and the most expensive ones exceed $500,000. The Biologics Price Competition and Innovation Act ("BPCIA") was passed in 2010 to lower prices by providing a new regulatory pathway in approving biosimilars--copies of brand-name biologics. Yet, the BPCIA's promised regulation of drug prices has not materialized partly due to brand-name companies' vast patent portfolios, also known as patent thickets. This Note analyzed all BPCIA patents disputed in BPCIA litigations and found that over half of the asserted patents are manufacturing method patents, many of which were filed years after FDA approval. Given the nonproduct-specific nature of these patents and stringent FDA requirements, these inventions are not only unnecessary, but are also unlikely to be practiced when producing brand-name biologics. Regardless of their actual worth, these patents are extremely valuable to brand-name manufacturers because even a patent of marginal improvement can foreclose biosimilar access entirely. This Note proposes that brand-name manufacturers should be required to disclose related patents at the time of the FDA approval and share the FDA license application with biosimilar manufacturers. Further, Congress should eliminate the availability of injunctive remedies for these problematic assertions of patents. [ABSTRACT FROM AUTHOR]

The article informs that companies seeking Food and Drug Administration (FDA) approval for their medical products are dramatically shifting human research overseas. It mentions FDA must use the funds solely for mutually agreed upon functions, predominantly speeding the pace of product approvals; and also mentions clinical trials offer the assessment of the efficacy and safety of new medical products.

Prolonged waiting to access health care is a primary concern for nations aiming for comprehensive effective care, due to its adverse effects on mortality, quality of life, and government approval. Here, we propose two novel bargaining frameworks to reduce waiting lists in two-tier health care systems with local and regional actors. In particular, we assess the impact of 1) trading patients on waiting lists among hospitals, the 2) introduction of the role of private hospitals in capturing unfulfilled demand, and the 3) hospitals' willingness to share capacity on the system performance. We calibrated our models with 2008–2018 Chilean waiting list data. If hospitals trade unattended patients, our game-theoretic models indicate a potential reduction of waiting lists of up to 37%. However, when private hospitals are introduced into the system, we found a possible reduction of waiting lists of up to 60%. Further analyses revealed a trade-off between diagnosing unserved demand and the additional expense of using private hospitals as a back-up system. In summary, our game-theoretic frameworks of waiting list management in two-tier health systems suggest that public–private cooperation can be an effective mechanism to reduce waiting lists. Further empirical and prospective evaluations are needed. [ABSTRACT FROM AUTHOR]

Summary: Background The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) was established in 2004. Since then, various pieces of legislation, notices, and guidelines have been issued, and the regulatory approval pathways for domestic drugs have been diversified. However, the effects of these measures have not been fully examined. We examined the impact of these measures on the approval of antineoplastic drugs and the design of pivotal clinical trials for efficacy assessment by the PMDA. Methods We collected data on the antineoplastic drugs approved by the PMDA in fiscal years 2004–2019. We extracted the approval review pathways and the pivotal clinical trial designs from the PMDA review reports, and analyzed them to identify patterns. Results In total, 387 indications in oncology were approved by the PMDA in fiscal years 2004–2019, or 365 indications excluding multiple regulatory pathways. The number of approved indications generally increased year on year (p < 0.001). The largest number of approved indications was under the Orphan Drug Designation (31%, 114/365) and this continues to increase (p < 0.001). In the 288 indications for which clinical trial data were submitted for review, the pivotal clinical trial designs changed significantly (p < 0.001) after the guideline on clinical evaluation for antineoplastic drugs was revised in 2006. Conclusion The number of indications in oncology approved by the PMDA has been increasing over the past 16 years, alongside changes in regulatory pathways. The 2006 guideline on clinical evaluation had a particular impact on pivotal clinical trial designs. [ABSTRACT FROM AUTHOR]