Postmarketing Surveillance System Research Articles

Short-Term Training, a Useful Approach for Sustainable Pharmacovigilance Knowledge Development in Tanzania, Kenya, Ethiopia and Rwanda.

Continuous professional development among stakeholders involved in drug safety monitoring and surveillance is imperative in strengthening pharmacovigilance (PV) systems. The "Pharmacovigilance infrastructure and post-marketing surveillance system capacity building for regional medicine regulatory harmonization in East Africa" (PROFORMA) project aims to enhance the national PV infrastructure, post-marketing surveillance systems and clinical trial regulatory capabilities in Ethiopia, Tanzania, Kenya and Rwanda. To achieve this, training, including short-term training (STT) activities, at various levels is required. This article aims to describe the experiences of the authors during the development and implementation of STT in an attempt to improve the PV training landscape of these countries. To identify gaps, a baseline assessment of PV teaching and practices at the national medicines regulatory authorities (NMRAs) and medical universities was conducted. Five successive training sessions, tailored to each country's specific needs and regulatory environments, were conducted; three focusing on fundamental concepts in PV and two dedicated to training-of-trainers courses. The training targeted staff from PV units of the NMRAs and medical universities. Enabling participation from all four countries in the same training fostered cross-country learning and collaboration. The contribution of STT to university education and the operational methodologies within NMRAs are explored, showcasing the impact on knowledge transfer and skill development in each country. In conclusion, by investing strategically in STT activities and fostering partnerships with academic institutions and NMRAs, we demonstrated a sustainable approach to PV capacity strengthening in resource-limited settings. The success of this model underscores its potential for adoption and replication across the African continent, offering a valuable framework for strengthening drug safety regulation and ultimately protecting public health.

Use of Artificial Intelligence in Medical Devices for Post-Market Surveillance

Artificial intelligence (AI) has emerged as a transformative tool in post-market surveillance (PMS) for monitoring the safety and performance of medical products. This article explores the role of AI in optimizing PMS practices, focusing on its applications in signal detection, risk assessment, and regulatory compliance. By harnessing machine learning algorithms and big data analytics, AI facilitates the automated analysis of real-world evidence, including patient outcomes data, adverse event reports, and electronic health records. Through pattern recognition and anomaly detection, AI algorithms enable the early identification of potential safety issues and facilitate timely interventions to mitigate risks. Moreover, AI-driven PMS systems enhance regulatory oversight by providing regulators with comprehensive and actionable insights into product safety profiles and emerging trends. However, concerns regarding data privacy, algorithm bias, and interpretability underscore the need for transparent and ethically responsible AI deployment in PMS frameworks.

Post-Market Surveillance of Medical Devices Using AI

Artificial intelligence (AI) has emerged as a transformative tool in post-market surveillance (PMS) for monitoring the safety and performance of medical products. This article explores the role of AI in optimizing PMS practices, focusing on its applications in signal detection, risk assessment, and regulatory compliance. By harnessing machine learning algorithms and big data analytics, AI facilitates the automated analysis of real-world evidence, including patient outcomes data, adverse event reports, and electronic health records. Through pattern recognition and anomaly detection, AI algorithms enable the early identification of potential safety issues and facilitate timely interventions to mitigate risks. Moreover, AI-driven PMS systems enhance regulatory oversight by providing regulators with comprehensive and actionable insights into product safety profiles and emerging trends. However, concerns regarding data privacy, algorithm bias, and interpretability underscore the need for transparent and ethically responsible AI deployment in PMS frameworks.

2024 Update on Postmarketing Nutrivigilance Safety Profile: A Line of Dietary Food Supplements Containing Red Yeast Rice for Dyslipidemia.

IntroductionConsidering lack of a European standardized postmarketing food supplement surveillance system, some member states and companies have developed their own approaches to monitoring potential AEs to secure a high level of product safety. This paper updates 2021 results of the use of a nutrivigilance system in monitoring the incidence of spontaneously reported suspected AEs associated with RYR-containing food supplements.Material and methodsWe report the data from a product marketed under the trademark Armolipid/Armolipid Plus. Postmarketing information was collected in a voluntary nutrivigilance system established by the manufacturing company (Meda Pharma SpA, a Viatris Company, Monza, Italy). From 1st October 2004-31st December 2023, this system captured cases of suspected AEs spontaneously reported by consumers, healthcare professionals, health authorities, regardless of causality.ResultsThe total number of case reports received mentioning the RYR-food supplement product line increased to 1186, in which 1904 AEs were reported. The total reporting rate of AEs was estimated to be 0.049% of 3,880,865 exposed consumers. Of the 1186 cases, 28 (0.0007%) included suspected SAEs. After careful investigation, 9 cases (0.0002%) and 12 AEs were assessed by the manufacturer as serious and potentially related to exposure to the above-mentioned RYR-based nutraceutical. Off-label reports linked to the newly introduced limitation at 70 years of age were observed, in contrast to the previous analysis.ConclusionsThese updated results confirm a very low incidence of RYR suspected AEs. Consumer safety of food supplements could be generally improved by raising awareness of the importance of following the indications and warnings detailed in a food supplement’s labelling.

P.021 Nonclinical studies of abuse potential with dual orexin-receptor antagonists: concordance with real-world use

Background: Traditional insomnia drugs enhance gamma-aminobutyric acid and are associated with abuse/dependence. Dual orexin-receptor antagonists (DORAs) represent an alternate mechanism promoting wakefulness, rather than inhibition. Nonclinical studies indicate DORAs do not demonstrate abuse potential. Nonetheless, based on human abuse potential (HAP) studies and lack of postmarketing data at approval, DORAs are Schedule 4 controlled substances. However, HAP studies may not predict real-world abuse-potential risk. Methods: Adverse events with preferred terms (PTs) of drug-withdrawal-syndrome, drug-abuse, and drug-dependence were evaluated from Eisai’s ongoing global postmarketing safety surveillance system in the US, Canada, and Japan (20/Dec/2019–30/Sep/2023) and the FDA Adverse Event Reporting System (FAERS; 01/Jan/2015–30/Jun/2023). In FAERS, reports of those PTs from DORAs (lemborexant/suvorexant/daridorexant) were compared with zolpidem and with benzodiazepines approved for patients with insomnia (estazolam/temazepam/triazolam). Results: Since lemborexant’s approval, few of the 3 PTs were reported in Eisai’s surveillance system (~0.15 cases per million patient-days of global exposure). Reports in FAERS for PTs of drug-withdrawal-syndrome, drug-abuse, and drug-dependence for DORAs (10,202 reports) were <0.1%/<0.1%/0.1%, respectively. Reports for benzodiazepines (5534 reports) were 0.8%/12.9%/3.7%, respectively, and 1.0%/9.1%/5.3% for zolpidem (18,330 reports), respectively. Conclusions: Abuse potential may be better represented by nonclinical studies and national surveillance systems, suggesting DORAs may not pose meaningful abuse potential and related risks.

Abstract 12454: Weak Supervision Enables Scalable Post-Market Surveillance on Medical Wearables

Introduction: With the advent of consumer-facing devices that can render atrial fibrillation (AF) pre-diagnosis, medical wearables now have the potential to affect diagnosis rates and medical care. Post-market surveillance is necessary to understand the impact of wearables on patient outcomes and health care utilization, but is hindered by the lack of codified terms in EHR that capture wearable use. Research Questions: Constructing a post-market surveillance system therefore requires a classifier that identifies mentions of AF pre-diagnosis in unstructured EHR data. However, fine-tuning classifiers require large, hand-labeled training sets that can be costly to generate. It is unclear whether a scalable surveillance system could be built for wearables. Methods: Two weakly-supervised approaches were evaluated to reduce clinical note labeling overhead: one using programmatic codes, and the other using prompts to large language models (LLMs). Probabilistically labeled notes were then used to fine-tune a classifier, which identified patients with AF pre-diagnosis mentions. A retrospective cohort study was conducted, where the characteristics and care patterns of patients identified by the classifier were compared against those who did not receive pre-diagnosis. Results: Label model derived from prompt-based labeling heuristics using LLMs (precision = 0.67, recall = 0.83, F1 = 0.74) nearly achieved the performance of code-based heuristics (precision = 0.84, recall = 0.72, F1 = 0.77), while cutting down the cost to create a labeled training set. The classifier learned on the labeled notes accurately identified patients with AF pre-diagnosis (precision = 0.85, recall = 0.81, F1 = 0.83). Those patients who received pre-diagnosis exhibited different demographic and comorbidity characteristics, and were enriched for anticoagulation and eventual diagnosis of AF. At the index diagnosis, existence of pre-diagnosis did not stratify patients on clinical characteristics, but did correlate with anticoagulant prescription. Conclusion: Our work establishes the feasibility of an EHR-based surveillance system for wearable devices that render AF pre-diagnosis. Weakly-supervised approaches can be effective in reducing test set labeling costs.

Adverse events from HPV vaccination in Taiwan

The safety of human papillomavirus (HPV) vaccines has been evaluated continuously in pre-licensure clinical trials, post-marketing surveillance systems, and observational studies. Most studies have found no significant association between serious adverse events and HPV vaccination. However, these studies have focused on Western populations; similar studies focusing on Asian populations are insufficient. Our retrospective cohort study used the HPV-vaccination records of junior high-school adolescent girls aged 12–15 years between 2013 and 2018 in Taiwan’s National Immunization Information System and linked them to a registry for beneficiaries in Taiwan’s National Health Insurance Database (NHID) to establish the vaccinated group. We selected 19 serious diseases as serious adverse events. We compared the incidence rates of these serious adverse events between the vaccinated group and girls in the same age group population, and we calculated the standardized incidence ratio (SIR) to evaluate the risk of serious adverse events after HPV vaccination. Because of the onset of different types of diseases, we set three periods after the subjects received HPV vaccination: within 3 months, within 1 year, and during the study period (2013–2018). The results showed the incidence rates and the SIRs of 19 selected adverse events. Among the 19 selected serious adverse events, the disease with the highest incidence rate during the study period was fibromyalgia (73.23 cases per million population), and the disease with the lowest incidence rate during the study period was Crohn’s disease (0.15 cases per million population). The results showed no statistically significant increases in the risk of 19 selected serious adverse events and indicated no association between HPV vaccination and serious adverse events. Given the benefits and safety of HPV vaccination, our research can reduce concerns about vaccine side effects, inform health policies and improve public and clinician’s acceptance of HPV vaccine policy.

Community health workers in clinical research at the example of a phase IIIb/ IV antimalarial drug trial conducted in five African countries

Global health, particularly in underserved settings can benefit immensely from well-trained community health workers (CHWs) supporting primary healthcare interventions. They can reduce morbidity and mortality of infectious diseases like malaria. Disease control programs can particularly benefit from a tight link between CHWs and communities and several studies have shown the benefit of the participation of non-facility-based CHWs in malaria control program activities for reducing malaria-related mortality in children. Because CHWs are often part of and trusted by served communities, they can also be an important resource to address challenges faced by their communities. Where post-marketing surveillance systems are underserved, they can relay important information about suspected safety signals and factors affecting therapeutic effectiveness in their communities. The CANTAM-Pyramax® trial was a phase IIIb/ IV cohort event monitoring study conducted at six centers in five African countries. To assess real-world effectiveness and safety of the anti-malarial pyronaridine-artesunate in 8560 malaria episodes, follow-up was not primarily conducted by medical staff but by specifically trained CHWs. This perspective paper discusses how the participation of a CHW workforce can be of benefit for effectiveness trials in limited-resource settings, using the example of the CANTAM-Pyramax trial.

Thrombosis with thrombocytopenia syndrome (TTS) following adenovirus vector COVID-19 vaccination in Canada

IntroductionIdentifying and monitoring adverse events following vaccination contributed to the safety and effectiveness of COVID-19 mass vaccination campaigns. In March 2021, international reports emerged of an adverse event following vaccination with adenovirus vector COVID-19 vaccines (ChAdOx1-S [recombinant] and Ad26.COV2.S) of thrombosis with low platelet counts, referred to as thrombosis with thrombocytopenia syndrome (TTS). We described TTS reports in Canada following adenovirus vector COVID-19 vaccines and investigated whether the observed number of events were higher than expected. MethodsReports of TTS following receipt of ChAdOx1-S [recombinant] or Ad26.COV2.S meeting the Canadian case definition for TTS and diagnostic certainty levels 1–3 of the Brighton Collaboration case definition, submitted to the Canadian Adverse Events Following Immunization Surveillance System and Canada Vigilance Database between February 26, 2021 and October 31, 2022 were included. Demographics and characteristics of the TTS reports are described along with an analysis comparing the observed number of reports to the expected number. ResultsAs of October 31, 2022, 56 reports of TTS following administration of ChAdOx1-S [recombinant] and no reports following Ad26.COV2.S vaccines were reported in Canada, of which 37 had functionally positive anti-PF4 antibodies. The median age was 56 years; males accounted for 54 % of reports. Five deaths were reported. The observed number of reports exceeded the expected for all ages and sexes combined, as well as for males aged 30–49 and 60–69 years, and females aged 40–59 years. ConclusionBased on international surveillance data, Canada evaluated a statistical signal of TTS following adenovirus vector vaccines. The investigation of this signal demonstrated how post-market vaccine safety surveillance systems were successful in investigating rare adverse events during the rollout of COVID-19 vaccines in Canada. As adenovirus vector vaccines continue to be administered, characterization of the association between the vaccine and TTS informs immunization programs and policies.

Endovascular Aneurysm Repair Devices as a Use Case for Postmarketing Surveillance of Medical Devices

The US Food and Drug Administration (FDA) is building a national postmarketing surveillance system for medical devices, moving to a "total product life cycle" approach whereby more limited premarketing data are balanced with postmarketing surveillance to capture rare adverse events and long-term safety issues. To assess the methodological requirements and feasibility of postmarketing device surveillance using endovascular aneurysm repair devices (EVARs), which have been the subject of safety concerns, using clinical data from a large health care system. This retrospective cohort study included patients with electronic health record (EHR) data in the Veterans Affairs Corporate Data Warehouse. Implantation of an AFX Endovascular AAA System (AFX) device (any of 3 iterations) or a non-AFX comparator EVAR device from January 1, 2011, to December 21, 2021. The primary outcomes were rates of type III endoleaks and all-cause mortality; and rates of these outcomes associated with AFX devices compared with non-AFX devices, assessed using Cox proportional hazards regression models and doubly robust causal modeling. Information on type III endoleaks was available only as free-text mentions in clinical notes, while all-cause mortality data could be extracted using structured data. Device-specific information required by the FDA is ascertained using unique device identifiers (UDIs), which include factors such as model numbers, catalog numbers, and manufacturer-specific product codes. The availability of UDIs in EHRs was assessed. In total, 13 941 patients (mean [SD] age, 71.8 [7.4] years) received 1 of the devices of interest (AFX with Strata [AFX-S]: 718 patients [5.2%]; AFX with Duraply [AFX-D]: 404 patients [2.9%]; or AFX2: 682 patients [4.9%]), and 12 137 (87.1%) received non-AFX devices. The UDIs were not recorded in the EHR for any patient with an AFX device, and partial UDIs were available for 19 patients (0.1%) with a non-AFX device. This necessitated the development of advanced natural language processing tools to define the cohort of patients for analysis. The study identified a significantly higher risk of type III endoleaks at 5 years among patients receiving any of the AFX device iterations, including the most recent version, AFX2 (11.6%; 95% CI, 8.1%-15.1%) compared with that among patients with non-AFX devices (5.7%; 95% CI, 2.2%-9.2%; absolute risk difference, 5.9%; 95% CI, 2.3%-9.4%). However, there was no significantly higher all-cause mortality for any of the AFX device iterations, including for AFX2 (19.0%; 95% CI, 16.0%-22.0%) compared with non-AFX devices (18.0%; 95% CI, 15.0%-21.0%; absolute risk difference, 1.0%; 95% CI, -2.1% to 4.1%). The findings of this cohort study suggest that clinical data can be used for the postmarketing device surveillance required by the FDA. The study also highlights ongoing challenges to performing larger-scale surveillance, including lack of consistent use of UDIs and insufficient relevant structured data to efficiently capture certain outcomes of interest.

The safety assessment of tampons: illustration of a comprehensive approach for four different products.

We illustrate a comprehensive tampon safety assessment approach that assures products can be used safely. Material biocompatibility, vaginal mucosa assessment, vaginal microbiome evaluation, and in vitro assessment of potential risk of staphylococcal toxic shock syndrome expressed through growth of Staphylococcus aureus (S. aureus) and production of TSST-1 are the four essential portions of the approach. Post-marketing surveillance informs of possible health effects that warrant follow up. The approach meets or exceeds US and international regulatory guidance and is described through the example of four tampon products. Each product is comprised mostly of large molecular weight components (cotton, rayon, polymers) that cannot pass the vaginal mucosa, are widely used across the industry, and replete with a vast body of safety data and a long history of safe use in the category. Quantitative risk assessment of all small molecular weight components assured a sufficient margin of safety supporting their use. Vaginal mucosa assessment confirmed that pressure points, rough edges and/or sharp contact points were absent. A randomized cross-over clinical trial (ClinicalTrials.gov Identifier: NCT03478371) revealed favorable comfort ratings, and few complaints of irritation, burning, stinging, or discomfort upon insertion, wear, and removal. Adverse events were few, mild in severity, self-limited and resolved without treatment. Vaginal microbiota assessment in vitro presented no adverse effect on microbial growth. Culture-independent microbiome analyses from vaginal swab samples obtained during the clinical trial showed no differences attributable to tampon usage, but instead due to statistically significant subject-to-subject variability. Growth of S. aureus and TSST-1 toxin production in the presence of any of the four products in vitro were statistically significantly reduced when compared to medium control alone. The data from the four elements of the comprehensive safety assessment approach illustrated herein confirm that tampons evaluated using this system can be used safely for menstrual protection. A post-marketing surveillance system that monitors and responds to in-market experiences indicated in-use tolerability of the product among consumers, thus confirming the conclusions of the pre-marketing safety assessment.

Evaluating the Impact of Black Box Warning Updates on the Reporting of Drug-Related Adverse Events: a Cross Sectional Study of the FAERS Database

ABSTRACT Background The Food and Drug Administration (FDA)’s Adverse Event Reporting System (FAERS) is a post-marketing surveillance system which relies on spontaneous reports of adverse drug reactions (ADRs). Our objective was to evaluate how black box warning (BBW) updates impact ADR reporting rates. Research Design and Methods We searched MEDWATCH for all BBW updates issued between January 2014 and December 2016 and categorized them as new, major, and minor. Rates of relevant ADR reports from the FAERS database in the 4 years preceding and following a BBW update were assessed among the different BBW categories. Results Forty BBW updates were included (16 major, 3 new, and 21 minor). A meaningful increase in the proportion of relevant ADRs of all ADRs reported following BBW updates was documented for 53% of new or major updates and 24% of minor updates (p = 0.06). The median percentage of reported relevant ADRs increased by 5% following new and major BBW updates and decreased by 30% following minor BBW updates (p = 0.3). Conclusions Reporting of adverse events to the FAERS database is affected by the severity and timing of related BBW updates, highlighting the drawbacks of spontaneous reporting systems. Regulators should promote proactive pharmacovigilance strategies to cope with these limitations.

Structure of Adverse Events Following Immunisation against Coronavirus Infection (COVID-19) in the Kyrgyz Republic

There is considerable interest worldwide in developing safe and effective vaccines against COVID-19. Pharma-covigilance of adverse events following immunisation (AEFIs) is a key to making informed decisions regarding the global COVID-19 vaccination campaign. In the Kyrgyz Republic, there have been developed a national immunisation information system (IIS) for automated recording of vaccines, vaccinated persons, and AEFIs and a mobile application for AEFI reporting, called Den Sooluk.The aim of the study was to analyse the pattern of AEFIs against COVID-19 in the Kyrgyz Republic.Materials and methods: the study analysed the spontaneous safety reports submitted to the national IIS database through the Den Sooluk mobile application from 29.03.2021 to 25.09.2022.Results: according to the data available by 25.09.2022, the total number of vaccinated people in the country amounted to 2,940,082. At the time, the IIS database included 2111 AEFIs: 1 fatal (and coincidental), 3 severe and 2108 minor ones. AEFIs were more frequent in the young and middle-aged population (81.5%), than in the elderly (18.5%). The following AEFIs were reported: injection site pain (21.25%), fatigue (20.7%), headache (19.8%), body temperature above 38 °C (10.10%), miscellaneous symptoms (5.12%), chills (4.41%), dizziness (4.32%), sore throat (3.36%), myalgia (2.9%), and nausea (2.2%).Conclusions: all COVID-19 vaccines used in the Kyrgyz Republic can be considered adequately safe. Pharmacovigilance of AEFIs is an integral part of the requirements to ensure the safe use of vaccines, and collecting of spontaneous reports on AEFIs supports adequate functioning of the post-marketing surveillance system. It is essential to provide access to electronic information platforms to health professionals and patients in order to ensure vaccination transparency and coordination and enable quick and safe reporting of AEFIs associated with the use of COVID-19 vaccines.

A narrative review of vaccine pharmacovigilance during mass vaccination campaigns: Focus on myocarditis and pericarditis after COVID-19 mRNA vaccination.

Vaccines have had a tremendous impact on reducing the burden of infectious diseases; however, they have the potential to cause adverse events following immunization (AEFIs). Prelicensure clinical trials are limited in their ability to detect rare AEFIs that may occur in less than one per thousand individuals. While postmarketing surveillance systems have shown COVID-19 mRNA vaccines to be safe, they led to the identification of rare cases of myocarditis and pericarditis after COVID-19 vaccination that were not initially detected in clinical trials. In this narrative review, we highlight concepts of vaccine pharmacovigilance during mass vaccination campaigns and compare the approaches used in the context of myocarditis and pericarditis following COVID-19 vaccination to historical examples. We describe mechanisms of passive and active surveillance, their strengths and limitations, and how they interacted to identify and characterize the safety signal of myocarditis and pericarditis after COVID-19 mRNA vaccination. Articles were synthesized from a PubMed search using relevant keywords for articles published on vaccine surveillance systems and myocarditis and pericarditis after COVID-19 vaccination, as well asthe authors' collections of relevant publications and grey literature reports. The global experience around the identification and monitoring of myocarditis and pericarditis after COVID-19 mRNA vaccination has provided important lessons for vaccine safety surveillance and highlighted its importance in maintaining public trust in mass vaccination programmes in a pandemic context.

A new platform for post-marketing surveillance and real-world evidence data collection for substance-based medical devices

The recent passage of European Union (EU) Regulation 2017/745 on medical devices (MDs) has improved the classification of MDs and revised their approval process and the post-marketing evaluation of their safety and effectiveness, promoting transparency and post-marketing oversight in Europe. This new regulation can better ensure patient safety and provide new opportunities for therapeutic innovation. In addition, the new regulations include and define MDs made of substances or of combinations of substances (substance-based MDs: SBMDs). The impressive growth of the MD, including SBMDs, that have been marketed over the recent years has likely been a relevant factor fueling this change. MD regulation requires a major effort from both industry and regulatory bodies to comply with its provisions. Manufacturers should produce sufficient clinical evidence that an MD, under normal conditions of use, provides adequate performance and that the foreseeable risks and frequency of adverse events (AEs) have an acceptable minimum rate, taking into account the benefits provided. We describe how we implemented the post-marketing surveillance (PMS) system of SBMDs to properly deal with post-market monitoring and confirmation of safety and performance, including AEs and the benefit–risk evaluation, as required by the 2017/745 Regulation. The two pillars of this novel system are: 1) passive vigilance, i.e., spontaneous reporting and 2) active post-marketing clinical follow-up (PMCF) activities, which systematically gather, record, and analyze real-world data (RWD) on performance, quality, function, use, tolerability, and safety of an MD, collected through a dedicated, structured web platform. Active PMCF is achieved through a process of generation, validation, and administration of digital questionnaires to all stakeholders, i.e., patients, physicians, both general practitioners and specialists, and pharmacists. The technology, potential use, advantages, and limitations of this large source of RWD are also discussed.

Approaches to accelerating the study of new antiretrovirals in pregnancy.

IntroductionWomen who are pregnant or who could become pregnant experience delayed access to or underinformed use of important new antiretroviral (ARV) drugs because of traditional drug development processes that ostensibly aim to reduce potential harm but effectively fail to ensure that timely information about safe and effective use in pregnancy is available.DiscussionThe World Health Organization and International Maternal, Pediatric, Adolescent Antiretroviral Clinical Trials Network convened a year‐long workshop on “Approaches to Enhance and Accelerate Study of New Drugs for HIV and Associated Infections in Pregnant Women.” Workshop participants were tasked with defining key principles and optimal approaches to including pregnant women in pre‐ and post‐licensure trials in order to accelerate the availability of pharmacokinetic and safety data for new ARV agents in pregnancy. ARV efficacy in pregnancy and ARV efficacy for prevention of vertical transmission can be extrapolated from proof of efficacy in non‐pregnant adults, provided that drug levels in pregnancy are similar. However, short‐term safety and pharmacokinetics must be studied directly in pregnant women and should be conducted and included in initial licensure for all new ARVs. Accelerating the timeline for completion of pre‐clinical studies is essential for pregnancy short‐term safety and pharmacokinetic studies to be safely completed by the time a drug is licensed. Composite key pregnancy, birth and neonatal outcomes are critical for drugs expected to have broad use, and studies should be initiated at or soon after drug licensure. Teratogenicity risk cannot be feasibly assessed before drug licensure and will depend on robust post‐marketing surveillance systems. With some modifications, these principles will apply to ARVs used for prevention, two‐drug regimens, long‐acting ARVs and ARVs administered through novel delivery systems.ConclusionsImplementation of the proposed principles and framework will enhance and accelerate the study of new ARVs in pregnancy, resulting in more timely, equitable and informed access to new ARVs for pregnant women.

Pilot study of the Korean national breast implant registry: Experiences and lessons learned

To improve the safety and early detection of unexpected breast implant-related complications, the Korean Breast Implant Registry (K-BIR) was launched in 2020 in cooperation with the Korean Society of Plastic and Reconstructive Surgeons and the Korean Ministry of Food and Drug Safety, and a pilot study was conducted. This article provides an overview of our pilot study and experiences of the K-BIR. The dataset to be used in the pilot form of K-BIR was constructed by holding online surveys and meetings focusing on the global breast device registry's minimum dataset. A pilot study was implemented from April 1, 2020, to July 31, 2020, with six university teaching hospitals and four private clinics. During the pilot study period, 325 patients, 451 procedures, and 366 implants were entered into the K-BIR. The most common procedure registered was augmentation mammaplasty (30%) for cosmetic indications, followed by direct-to-implant breast reconstruction (27%). Smooth silicone implant was the most common type (73%) of implant used. A feedback survey after the pilot study included questions about the registration rate compared with an actual procedure, entry time, reasons for difficulty in entry, and additional data needed. The continuous maintenance and development of K-BIR will require an effective dataset, a strengthened legal system for an opt-out registry and personal data protection, various incentives for increasing participation rates, and an electronic platform that patients, manufacturers, and clinicians can easily access. K-BIR has the potential to provide quality assurance and outcomes for research and post-market surveillance systems for breast implants as well as methods for enhancing patient safety.

Materiovigilance Programme of India: Current status and way forward.

Postmarketing vigilance system for medical devices in India is not as vigorous as of drugs. W Materiovigilance involves post marketing surveillance of adverse events caused by medical devices. As per directive of WHO, many countries including India have established their own post marketing surveillance system. In India it is known as Materiovigilance Programme of India (MvPI). This article reviews the current state of MvPI, compares it with developed countries, identifies gaps, and recommends specific measure to strengthen the existing program.

An Overview of COVID-19 Vaccine Safety and Post-marketing Surveillance Systems.

The need for the safety monitoring of the COVID-19 vaccine is unprecedented. It is an ongoing process starting from different phases of clinical trials and continued to post-marketing to tackle the emergency used authorized COVID-19 vaccines across the world. Rapid detection, exchange, prioritization, and assessment of safety signals based on available real-world data, surveillance of Adverse events following immunization (AEFI), and adverse event of special interest (AESI) by studying the observed/expected cases. Enhanced collaboration, and availability of resources, tools, and methods will add to the lessons learned from previous experiences.

A Modular Approach to Combine Postmarket Clinical Follow-Up Studies and Postmarket Surveillance Studies

The European Medical Device Regulation 2017/745 (MDR) has its date of application in May 2021. This new legislation has refined and expanded the need of manufacturers to have a postmarket surveillance (PMS) system. According to this legislation, a postmarket clinical follow-up (PMCF) plan is also required. Manufacturers of high-risk medical devices are obliged to conduct both PMCF and PMS studies. There is thus the need to generate evidence from clinical data. The conduct of several studies for PMS and PMCF can be cumbersome. We therefore aim to present a modular approach to combine PMS and PMCF studies into a single study. We extracted the topics listed in the MDR, especially Annex XV, Section 3, the Good Clinical Practice for medical devices (EN 14155:2020, Annex A). In addition, we added topics according to the SPIRIT and the SPIRIT-PRO statement and created a draft clinical investigation plan (CIP). The CIP template is provided as part of the manuscript. The modular concept has passed the required regulatory and legal requirements for one specific study. A modular approach for combining PMCF and PMS studies in a single CIP has been developed and implemented, and it is ready for use. The provided CIP template should enable other researchers and groups to adopt this concept according to their needs.