Post-marketing Surveillance Research Articles

Reference, calibration and referral laboratories- a look at current European provisions and beyond.

European Union (EU) regulations on invitro diagnostics (IVD) and on serious cross-border threats to health provide for the establishment of European Reference Laboratories (EURLs) and their harmonization and cooperation with National Reference Laboratories (NRLs). While the EURLs under the IVD Regulation will be operational by 1 October 2024, the EURLs under the Regulation on serious cross-border threats to health will be operational by January 2025. Although NRLs may have been operating for a long time on the basis of national legislation, they should now cooperate with each other and with EURLs in a network of centers of excellence for the authorization and post-market surveillance of IVDs and for the epidemiological surveillance and control of communicable diseases. The term "reference laboratory" has long been used colloquially to refer to many kinds oflaboratories, regardless of their tasks, competencies, responsibilities and designation. A literature search and analysis confirmed this by showing that a considerable proportion of scientific publications in 2024 use the term "reference laboratory" inappropriately. In order to clarify the roles and functioning of EURLs and NRLs, we have evaluated the relevant current EU provisions and compared the findings with those of reference laboratories designated by other organizations, calibration (reference) laboratories and referral laboratories, which are simply referred to as "reference laboratories". With the forthcoming implementation of the EU regulations, at least the goals of providing safe and high-quality IVDs and adequate public health surveillance for communicable diseases appear to be achievable.

Diagnostic Accuracy of 18 F-FES PET/CT for the Detection of Recurrent and Metastatic Breast Cancer.

To evaluate the diagnostic value of 16α- 18 F-fluoro-17β-fluoroestradiol ( 18 F-FES) PET/CT for distant metastasis or recurrence in patients with estrogen receptor (ER)-positive breast cancer. Patients with ER-positive breast cancer and suspected of de novo metastasis or recurrence were retrospectively identified from a prospective cohort enrolled for a postmarketing surveillance study of 18 F-FES at our institution. Per-patient diagnostic accuracy was assessed using pathology or 2 or more standard-of-care imaging procedures with a minimum of 6 months of follow-up as the reference standard. The per-region detection rate of 18 F-FES PET/CT was evaluated and compared with that of standard-of-care imaging. Of the 162 included patients, 104 and 58 were suspected to have recurrence or de novo metastasis, respectively. The overall sensitivity and specificity of 18 F-FES PET/CT were 95% (95% confidence interval [CI], 89%-98%) and 89% (95% CI, 76%-96%), respectively. When stratified according to clinical settings, the sensitivity and specificity were 95% (95% CI, 88%-99%) and 96% (95% CI, 78%-100%), respectively, for detecting recurrence, and 94% (95% CI, 81%-99%) and 82% (95% CI, 60%-95%) for detecting distant metastasis. In region-based analysis, the overall detection rate of 18 F-FES PET/CT was significantly higher than that of standard-of-care imaging (92% [95% CI, 89%-94%] vs 83% [95% CI, 79%-87%], P < 0.001). 18 F-FES PET/CT showed excellent diagnostic performance in patients with ER-positive breast cancer suspected of de novo metastasis or recurrence.

Exploring SGLT-2 inhibitors and sarcopenia in FAERS: a post-marketing surveillance study

ABSTRACT Background The sodium-dependent glucose transporters 2 inhibitors (SGLT-2i) is associated with body weight loss but the composition of the losing weight remains unclear. Research design and methods Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi- item gamma Poisson shrinker (MGPS) algorithms, were employed to quantify the signals of SGLT-2i-associated musculoskeletal and connective tissue disorders AEs. Results The search retrieved a total of 3,206 cases of musculoskeletal and connective tissue disorder-related AEs during the reporting period. This included 1,061 cases for Canagliflozin, 1,052 cases for Dapagliflozin, 1,074 cases for Empagliflozin, and 19 cases for Ertugliflozin. Fifteen preferred terms (PTs) with significant disproportionality were retained. No musculoskeletal and connective tissue system-related AE signals were reported for Ertugliflozin. We identified a risk of muscle necrosis with Canagliflozin use, a risk of sarcopenia with Dapagliflozin use, and a chance of muscle atrophy with Dapagliflozin and Empagliflozin prescriptions. Most cases occurred within the first month after SGLT-2i initiation, and AEs can persist beyond 360 days of use. Conclusions Our study identified potential new musculoskeletal and connective tissue disorder-related AE signals associated with SGLT-2 inhibitors.

A prospective, observational, multi-center, post-marketing safety surveillance study of the GSK combined vaccine against diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b invasive infections (DTaP-IPV/Hib) in South Korean infants

ABSTRACT In South Korea, a combined vaccine against diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b invasive infections (DTaP-IPV/Hib) is available since 2018 for vaccination of infants from the age of 2 months. This prospective, observational, non-comparative, post-marketing study evaluated the real-world safety of DTaP-IPV/Hib primary vaccination in eligible South Korean infants from the age of 2 months between 2018 and 2022. Infants were followed up for 30 days after each vaccine dose to assess the proportion of infants experiencing any adverse event (AE), including adverse drug reactions (ADRs), unexpected AEs, and serious AEs/serious ADRs (SAEs/SADRs). Of 660 infants vaccinated during the study period, 646 were included in the total safety cohort. A total of 194 AEs were reported in 143 (22.1%) infants; 158 AEs occurred after the first dose in 130 (20.1%) infants, 21 after the second dose in 20 (13.4%) infants, and 11 after the third dose in ten (8.1%) infants. The most frequent AEs by Medical Dictionary for Regulatory Activities Preferred Terms terminology were pyrexia (13.3%), injection site swelling (5.1%), and irritability (1.7%). Most of the AEs were mild, resolved without a medical visit, and were classified as possibly related to vaccination. The incidence proportions of ADRs, unexpected AEs, and SAEs/SADRs were 19.4%, 4.3%, and 0.9%, respectively. All SAEs/SADRs resolved after hospitalization or emergency room visit, and one event was possibly related to vaccination. These results are in line with the approved label and other national/international studies, confirming the acceptable safety profile of DTaP-IPV/Hib in the South Korean pediatric population.

Evaluating the Efficacy of Cosmetic Product Safety Regulations in Malaysia: The Role of the National Pharmaceutical Regulatory Agency (NPRA) and Industry Compliance

Various legislative measures, such as the Sale of Drugs Act 1952, Control of Drugs and Cosmetics Regulations 1984, Poison Act 1952, Guidelines for Control of Cosmetic Products 2022, and other directives introduced by the NPRA in Malaysia, are intended to control the safety of cosmetic products. Despite these existing laws and directives, cosmetic products containing hazardous ingredients persist in the Malaysian market. NPRA reportedly received 1,041 complaints about cosmetic products in 2022, while its website also displays an annual increase in cases involving cosmetic products that contain hazardous ingredients. The persistent presence of harmful cosmetic products in the market highlights significant gaps in efforts to control hazardous cosmetic products. This study examined the efficacy of cosmetic product safety regulations in Malaysia, focusing on the role of the National Pharmaceutical Regulatory Agency (NPRA) and industry compliance. This qualitative study gathered data from library databases and conducted semi-structured interviews with NPRA officers, cosmetic manufacturers, and cosmetic industry experts. Findings suggest that despite the extensive nature of the regulatory framework, its implementation, which heavily relies on self-regulation and post-market surveillance, requires serious improvement. While some cosmetic producers adhere to Good Manufacturing Practice (GMP) standards, there are still persistent issues related to product notification, misuse of self-regulation, and inadequate penalties for non-compliance. Therefore, an intensive awareness campaign aimed at cosmetic manufacturers is necessary to ensure the production of safe cosmetic products. Consumers must play their role in helping the NPRA control the sale of hazardous cosmetic products by performing safety checks before purchasing them.

8348 A Rare Case Of Liraglutide-Associated Angioedema Requiring Emergent Intubation

Abstract Disclosure: T. Amin: None. A. Mararenko: None. J. Cheng: None. R. Ong: None. S. Holland: None. K. Hu: None. Introduction: Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used in the management of type 2 diabetes mellitus to enhance glycaemic control. While generally considered safe, recent reports indicate an increasing frequency of adverse drug reactions, with gastrointestinal symptoms such as pancreatitis becoming more prevalent. This case report highlights a rare occurrence of angioedema induced by the GLP-1 receptor agonist, Liraglutide. Case A 58-year-old Type 2 diabetic male presented with rapidly progressing tongue swelling, abdominal discomfort, and watery diarrhea, six hours after initiating Liraglutide therapy. On presentation, he was hemodynamically stable, afebrile, maintaining adequate oxygenation on room air. On examination, the patient was in moderate distress with generalized tongue swelling protruding out, with no swelling of eyelids or lips. No rashes were noted on exposed skin and clear breath sounds without wheezing on lung examination. Due to concern for an impending airway compromise, the patient was intubated. Chart review showed he had an episode of self-resolving tongue swelling a few months back, at which time he was taken off his Angiotensin receptor blocker. 2 weeks ago, he was started on a new brand of GLP-1 receptor agonist (Liraglutide) to achieve optimal glycemic control. No other drug allergies or allergic reactions were reported. C1-Esterase panel, eosinophil count, and inflammatory markers were within normal limits.On admission, Liraglutide was discontinued, he was placed on a basal-bolus insulin regimen, received methylprednisolone, famotidine, and diphenhydramine Subsequent improvement allowed for extubation on the third day, and the patient was discharged with plans to discontinue Liraglutide and an epinephrine pen for precautionary use. Conclusion: This case represents a rare and severe manifestation of angioedema associated with Liraglutide use in a diabetic patient. While angioedema has been infrequently reported with other GLP-1 receptor agonists such as Exenatide and Dulaglutide , our case underscores the importance of clinicians' awareness regarding this potential life-threatening complication with Liraglutide. Post-marketing surveillance data suggest that anaphylactic reactions with Liraglutide may occur rarely, emphasizing the need for vigilance among healthcare providers. Presentation: 6/2/2024

Spectrum and Incidence of Adverse Reactions Post Immunization in the Taiwanese Population (2014-2019): An Analysis Using the National Vaccine Injury Compensation Program.

Background: Post-marketing surveillance is crucial for gathering data on vaccine reactogenicity, enhancing public trust in immunization, and promoting vaccine uptake. This study aims to characterize adverse events following immunization (AEFIs) and estimate the incidence rates of adverse reactions (ARs) associated with vaccines included in Taiwan's Expanded Program on Immunization (EPI). This study utilizes data from Taiwan's Vaccine Injury Compensation Program (VICP). Methods: Vaccine injury claims submitted to the VICP between 2014 and 2019 were analyzed. ARs were defined as AEFIs adjudicated as "related" or "indeterminate" by the VICP committee. Data on the annual number of vaccine doses administered were obtained from the Taiwan CDC, which helped calculate the AR incidence rates. Results: A total of 491 AEFI claims were reviewed, with 327 (66.6%) categorized as ARs. The AEFIs were mainly associated with the Bacillus Calmette-Guérin (BCG) vaccine (43.4%) and the seasonal influenza vaccine (22.0%). Most EPI vaccines demonstrated low AR incidence rates, ranging from 1.68 to 13.6 per million doses, with the exception of BCG, which exhibited 162.5 ARs per million doses. Shifting BCG immunization from below 5 months to at least 5 months reduced osteomyelitis incidence significantly, from 41.4 to 7.9 (p = 0.0014), but increased abscess and lymphadenitis cases. Conclusions: EPI vaccines in Taiwan are highly safe, with minimal AR incidences in the general population. The BCG vaccine remains an exception, occasionally causing severe ARs like osteomyelitis. Adjusting the immunization schedule to an older age may mitigate some of these adverse effects.

Adverse Events of the Over The Scope Endoscopic Clips and Cutters: A MAUDE Database Analysis

The OVESCO® clip system, including the Over-The-Scope Clip (OTSC) and Full-Thickness Resection Device (FTRD), has demonstrated efficacy in managing various gastrointestinal pathologies. However, real-world data on device malfunctions and patient complications are limited. This study aimed to analyze adverse events associated with OVESCO® clips and cutters reported to the FDA Manufacturer and User Facility Device Experience (MAUDE) database. The MAUDE database was searched for reports related to OVESCO® clips and cutters from January 1, 2007, to August 30, 2024. Event date, device type and model, manufacturer, event type, device problem, and patient complications were extracted. Descriptive statistics were used to summarize the findings. Forty-two reports were identified, with 41 involving OVESCO® clips and one involving an OVESCO® cutter. The most common device problem for OVESCO® clips was failure to deploy (61.0%), followed by unintended deployment or misfiring (17.1%). Gastrointestinal perforation was the most frequently reported patient complication (60%). The OVESCO® cutter report described device component breakage and foreign body retention. No clear trends in adverse event reporting were observed over the study period. OVESCO® clips and cutters are associated with potential device malfunctions and patient complications, particularly gastrointestinal perforation. The findings highlight the need for careful patient selection, meticulous technique, and close post-procedural monitoring. Collaborative efforts among stakeholders are essential to optimize device safety and efficacy. Continued post-marketing surveillance and real-world data analysis are crucial for monitoring the performance of endoscopic devices and improving patient outcomes.

A scoping review of reporting gaps in FDA-approved AI medical devices

Machine learning and artificial intelligence (AI/ML) models in healthcare may exacerbate health biases. Regulatory oversight is critical in evaluating the safety and effectiveness of AI/ML devices in clinical settings. We conducted a scoping review on the 692 FDA-approved AI/ML-enabled medical devices approved from 1995-2023 to examine transparency, safety reporting, and sociodemographic representation. Only 3.6% of approvals reported race/ethnicity, 99.1% provided no socioeconomic data. 81.6% did not report the age of study subjects. Only 46.1% provided comprehensive detailed results of performance studies; only 1.9% included a link to a scientific publication with safety and efficacy data. Only 9.0% contained a prospective study for post-market surveillance. Despite the growing number of market-approved medical devices, our data shows that FDA reporting data remains inconsistent. Demographic and socioeconomic characteristics are underreported, exacerbating the risk of algorithmic bias and health disparity.

A Comprehensive Assessment of Quality of Antimalarial Medicines in Mainland Tanzania: Insights from Five Years of Postmarket Surveillance.

Sustainable access to high-quality antimalarial medicines is pivotal to achieving universal and effective malaria control. Poor-quality antimalarial medicines are prevalent in sub-Saharan Africa, impeding malaria control initiatives and claiming the lives of many children. Regular monitoring of the quality of antimalarial medicines is crucial to ensure the quality of service to the community. A cross-sectional study using a postmarket surveillance (PMS) approach was conducted from 2019 to 2023. Samples were collected from the port of entry, local manufacturers, and various distribution outlets in 15 regions of mainland Tanzania. The samples were subjected to tier 1 evaluation, comprising a product information review (PIR) and identification using the Global Pharma Health Fund-Minilab® techniques. Samples that failed the identification tests and 10% of the samples from distribution outlets that passed the tests were subjected to confirmatory testing (tier 2), which included assays, related substances, dissolution, and sterility per the pharmacopeial monographs. During five annual PMSs, 2,032 antimalarial samples were collected and subjected to quality tests. All samples complied with the standard specifications for identity, dissolution, related substances, sterility, physical evaluation, disintegration, and assay. A total of 292 (55.5%) tested samples failed the PIR evaluation, with incomplete package information in leaflets contributing to 64.7% of all deviations. Antimalarial medicines circulating in the mainland Tanzanian market meet expected quality standards. Continuous monitoring of the quality of antimalarial medicines is recommended.

Safety assessment of the world’s first novel cocktail of two monoclonal antibodies in WHO category-III animal-bite patients

ABSTRACT Background: Rabies, a zoonotic disease, poses a significant global public health challenge, and post-exposure prophylaxis (PEP) is crucial for prevention. Monoclonal antibodies (mAbs) have emerged as a promising alternative to rabies immunoglobulins due to their high efficacy and standardized manufacturing process. Materials and Methods: A prospective, open-label post-marketing surveillance study was conducted with patients of WHO category-III suspected rabid animal bites. TwinRab™, a novel cocktail of docaravimab and miromavimab, was administered at a dosage of 40 IU/kg in and around the wound, along with the anti-rabies vaccine, which was administered intradermal as per Thai Red Cross regimen. Results: In this study, 200 subjects received TwinRab™ with a 100% completion rate. Three (1.5%) patients showed solicited local AEs, and two (1%) patients showed solicited systemic AEs, which were resolved after appropriate treatment intervention. The overall tolerability assessment showed positive ratings from doctors (94%) and patients (74%). Conclusion: The post-marketing surveillance study demonstrated the safety of TwinRab™ in patients who experienced category-III suspected rabid animal bites, thereby supporting its potential as an alternative option for PEP in the management of animal bite for the prevention of rabies.

Regulatory requirements for dietary supplements under food safety and standards authority of India (FSSAI) in comparison with Cambodia

The Food Safety and Standards Authority of India (FSSAI) regulates dietary supplements in India; this study looks at such regulations and compares them with those in Cambodia. Regulations regarding production, labelling, licensing, and advertising are compared and contrasted. Although both nations have set up regulatory systems, the FSSAI guidelines in India are more extensive and have more stringent licensing and labelling requirements. The laws in Cambodia, on the other hand, are more focused on post-market surveillance and are less specific. The present study underscores the necessity of achieving regulatory requirements harmonization and improvement in order to safeguard consumer safety and foster the expansion of the dietary supplement business in both nations. The results will provide insight into the regulatory environment around dietary supplements in India and Cambodia for consumers, industry stakeholders, and policymakers1.

Regulatory requirements for the approval of anti-cancer drugs as per CDSCO in India comparison with Singapore

This study examines the regulatory requirements for anticancer medications in Singapore and India are compared in this abstract. It draws attention to the frameworks set up by Singapore's Health Sciences Authority (HSA) and India's Central Drugs Standard Control Organization (CDSCO). The procedures for clinical studies, approval schedules, and post-marketing surveillance are among the main distinctions. Singapore places a strong emphasis on strict safety and efficacy criteria, whereas India stresses a quicker clearance process to address pressing healthcare needs. The investigation highlights how various regulatory methods affect patient access, innovation, and medicine supply in both nations. Recent decades have seen extraordinary improvements in the discovery of anticancer medications, transforming both cancer treatment and patient outcomes. With an emphasis on the main areas of anticancer therapeutics—chemotherapy, targeted therapy, immunotherapy, and hormone therapy—this study offers a thorough summary of the state of the field. We examine each drug class's methods of action, effectiveness, and difficulties while showcasing more recent developments like immune checkpoint inhibitors and CAR-T cell therapy. We also go over side effects, drug resistance, and how tailored medicine might improve the effectiveness of treatment. A look is also given to new developments in drug research, such as the application of nanotechnology and AI-driven drug discovery. The review attempts to shed light on the changing tactics used to fight cancer and the potential paths for anticancer medication development.

Post-marketing surveillance framework of cell and gene therapy products in the European Union, the United States, Japan, South Korea and China: a comparative study

BackgroundCell and gene therapy products (CGTPs) often receive accelerated approvals, lacking comprehensive long-term safety and efficacy data, which can raise significant safety concerns. This research aims to study the post-marketing surveillance (PMS) of CGTPs in the European Union (EU), the United States (US), Japan, South Korea, and China, to offer insights for the development of a secure and standardized post-marketing regulatory framework for CGTPs.MethodsRelated regulations and the implementation effect of PMS for approved CGTPs were studied searching PubMed, CNKI, and the official websites of the European Medicines Agency, the US Food and Drug Administration, Japan’s Pharmaceuticals and Medical Device Agency, South Korea’s Ministry of Food and Drug Safety, and the National Medical Products Administration of China.ResultsCompared to those in China, the guidelines of PMS for CGTPs in the EU, the US, Japan, and South Korea was more comprehensive. Notably, the EU had dedicated regulations and supporting guidelines of PMS. Of the 26 CGTPs approved in the EU, 88% were under additional monitoring, 38% received conditional marketing authorization, and 12% were authorized under exceptional circumstances, with 77% designated as orphan drugs. The US had released 34 guidelines specifically for CGTPs which, forming the foundation of post-marketing risk management. Among the 27 CGTPs approved in the US, 22% were required to perform risk evaluation and mitigation strategies, 37% added black box warnings in the package inserts, 63% mandated to post-marketing requirements, and 15% subject to post-marketing commitments. In Japan, stringent supervision measures encompassing all-case surveillance (79%) and re-examination (53%) were applied to the 19 approved CGTPs, with 21% approved through conditional and time-limited approval. The PMS for CGTPs in South Korea, mainly included PSUR, re-examination, and re-evaluation. China had introduced several relevant regulations, which consisted of general statements and lacked detailed guidance.ConclusionsThis study demonstrates that the regulatory policies of PMS for CGTPs in the EU, the US, Japan, and South Korea were comprehensive. The implementation of PMS for CGTPs in the EU, the US, and Japan was well developed. This knowledge holds valuable insights for China’s future learning and development in this field.

Developing large language models to detect adverse drug events in posts on X

ABSTRACT Adverse drug events (ADEs) are one of the major causes of hospital admissions and are associated with increased morbidity and mortality. Post-marketing ADE identification is one of the most important phases of drug safety surveillance. Traditionally, data sources for post-marketing surveillance mainly come from spontaneous reporting system such as the Food and Drug Administration Adverse Event Reporting System (FAERS). Social media data such as posts on X (formerly Twitter) contain rich patient and medication information and could potentially accelerate drug surveillance research. However, ADE information in social media data is usually locked in the text, making it difficult to be employed by traditional statistical approaches. In recent years, large language models (LLMs) have shown promise in many natural language processing tasks. In this study, we developed several LLMs to perform ADE classification on X data. We fine-tuned various LLMs including BERT-base, Bio_ClinicalBERT, RoBERTa, and RoBERTa-large. We also experimented ChatGPT few-shot prompting and ChatGPT fine-tuned on the whole training data. We then evaluated the model performance based on sensitivity, specificity, negative predictive value, positive predictive value, accuracy, F1-measure, and area under the ROC curve. Our results showed that RoBERTa-large achieved the best F1-measure (0.8) among all models followed by ChatGPT fine-tuned model with F1-measure of 0.75. Our feature importance analysis based on 1200 random samples and RoBERTa-Large showed the most important features are as follows: “withdrawals”/”withdrawal”, “dry”, “dealing”, “mouth”, and “paralysis”. The good model performance and clinically relevant features show the potential of LLMs in augmenting ADE detection for post-marketing drug safety surveillance.

Real-world safety and effectiveness of lenvatinib in unresectable hepatocellular carcinoma in Korea: post-marketing study.

Aim: This post-marketing surveillance study evaluated the safety and effectiveness of lenvatinib as first-line treatment for unresectable hepatocellular carcinoma in Korea.Materials & methods: Adverse drug reactions (ADRs) and other safety and effectiveness end points were assessed in patients who initiated lenvatinib according to the approved label in republic of Korea.Results: Among 658 lenvatinib-treated patients, ADRs were reported in 57.8%; ADRs grade ≥3 in 13.5%. The most common grade ≥3 ADRs were asthenia (1.2%) and hepatic encephalopathy (1.2%). Physician-reported tumor responses (n=511) were complete (1.0%) or partial (12.9%) response and stable (45.2%) or progressive disease (40.9%); objective response rates were higher with longer lenvatinib treatment duration (p<0.001).Conclusion: Lenvatinib was generally well tolerated and effective in real-world clinical practice in Korea.Clinical trial registration: ClinicalTrials.gov NCT05225207.

Emicizumab revolution in treating Hemophilia

HemophiliaA (H.A.) has beenanuncommon hereditary X-linked bleeding disorder indicated by clotting factorVIII (FVIII)deficiency, leading to impaired hemostasis. H.A. affects approximately one in 5,000male births in the U.S., often resulting in spontaneous joint bleeding, chronic pain, and an increased risk of cerebral hemorrhage. Prophylactic treatment with FVIII replacement or the bispecific antibody emicizumab has become a crucial strategy to prevent bleeding episodes and long-term tissue damage. Emicizumab, approved by the FDA &amp; EMA in2018, mimics FVIII activity by binding to activated factorIX (FIXa) &amp; factorX (F.X.), facilitating blood clotting regardless of FVIII inhibitors. The development of emicizumab involved extensive bioengineering to optimize its safety, stability, and efficacy, leading to its successful application in clinical trials. These trials demonstrated that emicizumab significantly decreases the annualized bleeding rate in studied cases with or without inhibitors, including severe H.A. cases, with a favorable safety profile and minimal adverse events. Emicizumab's subcutaneous administration, high bioavailability, and predictable pharmacokinetics make it a practical option for H.A. prophylaxis. Despite its benefits, emicizumab can interfere with specific coagulation assays and may develop anti-drug antibodies (ADAs) in rare cases, potentially reducing its efficacy. Ongoing research and post-marketing surveillance continue to assess its long-term safety and effectiveness, making emicizumab a transformative treatment in managing hemophilia A.

Social Media as a Source of Information for the Detection of Adverse Drug Reactions in Post-Marketing Surveillance: A Review

INTRODUCTION. With the development of the Internet and the increasing availability of social networks and fora, patients have received an opportunity to share their medication experiences online. According to the guidelines on Good Pharmacovigilance Practices, social media can be considered an important additional source of patient-derived information in post-marketing surveillance, but the effectiveness of their use in detecting adverse drug reactions (ADRs) is still being investigated.AIM. This study aimed to analyse the results of relevant original studies and assess the potential of using social networks and online patient fora as a source of information on ADRs associated with the use of medicinal products.DISCUSSION. Published studies indicate that posts on social networks and patient fora describe both minor and serious ADRs, including new ADRs. The relevance of social media as a source of information about the safety of a medicinal product varies depending on several factors, including the medicinal product class and time on the market, as well as the platform demographics. Young users (18–44 years) are interested in online discussions about medicinal products for mental and reproductive system disorders. Users aged 45–64 years tend to discuss the use of medicinal products for chronic pain (including muscle pain), menopause, and gastritis. Discussions among users over 65 years old predominantly focus on medicinal products for diabetes, heart conditions, and muscle pain. People are much more likely to describe ADRs associated with the use of medicinal products for orphan diseases and cancer on fora for patients than on social networks in general, and vice versa for ADRs associated with the use of medicinal products for mental disorders. In addition, social media may be of interest as a source of information about cases of overdose, misuse and off-label use of medicinal products, and use of medicinal products during pregnancy and lactation.CONCLUSIONS. Social media can be a source of valuable information about the safety of medicinal products and the impact of ADRs on the quality of patients’ lives. Marketing authorisation holders can obtain new information about the safety of medicinal products by extending their safety monitoring strategies to include social media. Nevertheless, since the relevance of a particular social network or patient forum for the detection of ADR cases varies considerably, a preliminary assessment is necessary to ascertain the presence of information on the medicinal product of interest.

Real-world data to support post-market safety and performance of embolization coils: evidence generation from a medical device manufacturer and data institute partnership

BackgroundRecognizing the limitations of pre-market clinical data, regulatory authorities have embraced total product lifecycle management with post-market surveillance (PMS) data to assess medical device safety and performance. One method of proactive PMS involves the analysis of real-world data (RWD) through retrospective review of electronic health records (EHR). Because EHRs are patient-centered and focused on providing tools that clinicians use to determine care rather than collecting information on individual medical products, the process of transforming RWD into real-world evidence (RWE) can be laborious, particularly for medical devices with broad clinical use and extended clinical follow-up. This study describes a method to extract RWD from EHR to generate RWE on the safety and performance of embolization coils.MethodsThrough a partnership between a non-profit data institute and a medical device manufacturer, information on implantable embolization coils’ use was extracted, linked, and analyzed from clinical data housed in an electronic data warehouse from the state of Indiana’s largest health system. To evaluate the performance and safety of the embolization coils, technical success and safety were defined as per the Society of Interventional Radiology guidelines. A multi-prong strategy including electronic and manual review of unstructured (clinical chart notes) and structured data (International Classification of Disease codes), was developed to identify patients with relevant devices and extract data related to the endpoints.ResultsA total of 323 patients were identified as treated using Cook Medical Tornado, Nester, or MReye embolization coils between 1 January 2014 and 31 December 2018. Available clinical follow-up for these patients was 1127 ± 719 days. Indications for use, adverse events, and procedural success rates were identified via automated extraction of structured data along with review of available unstructured data. The overall technical success rate was 96.7%, and the safety events rate was 5.3% with 18 major adverse events in 17 patients. The calculated technical success and safety rates met pre-established performance goals (≥ 85% for technical success and ≤ 12% for safety), highlighting the relevance of this surveillance method.ConclusionsGenerating RWE from RWD requires careful planning and execution. The process described herein provided valuable longitudinal data for PMS of real-world device safety and performance. This cost-effective approach can be translated to other medical devices and similar RWD database systems.

Class I Recalls of Cardiovascular Devices Between 2013 and 2022 : A Cross-Sectional Analysis.

Cardiovascular devices account for one third of all Class I recalls, the U.S. Food and Drug Administration's (FDA) most severe designation, indicating a reasonable probability of "serious adverse health consequences or death." Understanding recalls and their causes is important for patient safety. To characterize Class I recalls of cardiovascular devices and the clinical evidence supporting authorization. In this cross-sectional study, cardiovascular device recalls from 1 January 2013 through 31 December 2022 were identified using the FDA's annual log. Information about devices was extracted from publicly available FDA decision summaries. The FDA Medical Device Recalls database. Cardiovascular devices with Class I recalls. Recalls were characterized by their causes and scope. Devices were characterized by their regulatory history (product code, special designations) and clinical evidence (premarket testing, postmarket surveillance). Clinical studies were analyzed for quality, including end point selection (clinical vs. surrogate, use of composites). From 2013 to 2022, there were 137 Class I recall events affecting 157 unique cardiovascular devices, of which 112 (71.3%) were moderate-risk 510(k) devices and 45 (28.7%) were high-risk premarket approval (PMA) devices. Recalls affected a median of 7649 units (IQR, 953 to 28 446) and were most commonly attributed to device design (43 [31.4%]). Forty-two (26.8%) devices had multiple Class I recalls. Thirty (19.1%) devices underwent premarket clinical testing (7 [6.2%] 510(k) devices, 17 [85.0%] PMA devices, and 6 [24.0%] PMA supplement devices). Most studies used surrogate (27 [79.4%]) and composite (24 [70.6%]) measures as primary end points. Twenty-two (48.9%) PMA devices had required postapproval studies, with 14 reporting delays. No 510(k) devices were subject to postmarket surveillance. Details about clinical testing may be missing from FDA summaries. Cardiovascular devices with Class I recalls were infrequently subjected to premarket or postmarket testing, with recalls affecting thousands of patients annually. None.