Adverse drug effect in the context of drug shortage: the CIRUPT prospective study from the French pharmacovigilance network.

OBJECTIVES: Drug shortages are of increasing concern to worldwide public health. The consequences of drug shortages for patient safety have been little studied, especially from a pharmacovigilance point of view. In this context, the network of French pharmacovigilance centres conducted the CIRUPT study (Conséquences Iatrogènes des RUPTures de stock/iatrogenic consequences of drug shortages) based on a prospective campaign of adverse effects occurring in the context of drug shortage notifications. METHODS: All notifications involving a shortage drug submitted to the French pharmacovigilance centres between 1 January 2020 and 30 June 2021 were collected and registered in the French national pharmacovigilance database with the standardised high level term 'product supply and availability issues' and with predefined keywords in the narrative section. RESULTS: 224 cases were included, involving mainly adverse drug reactions (ADRs) (n=131/224, 59%) and medication errors (n=51/224, 23%); 29% of the cases were serious. The most represented classes of shortage drugs were: vaccines (n=78/224, 35%); drugs for acid-related disorders (H2-receptor antagonists) (n=27/224, 12%); antineoplastic agents (n=17/224, 8%); and antiepileptics (n=15/224, 7%). In 82% of cases, the involved shortage drug was the subject of information delivered to health professionals by the National Agency for the Safety of Medicines and Health Products. Drug shortages were associated with an ADR related to replacement drugs in 59% (n=131/224) of the cases, drug inefficacy in 18% (n=41/224), and/or an aggravation of the underlying disease in 11% (n=25/224). CONCLUSIONS: From a pharmacovigilance point of view, a large diversity of anatomical therapeutic classes is involved and the risk related to drug shortages is not limited to drugs registered on 'major therapeutic interest or essential drug' lists. Information from health agencies is not sufficient to avoid the risks, and further strategies should be developed.

Exploring Safety in Gender-Affirming Hormonal Treatments: An Observational Study on Adverse Drug Events Using the Food and Drug Administration Adverse Event Reporting System Database.

BACKGROUND: People with gender dysphoria are treated with hormone therapy for gender reassignment. The indication of this therapy was initially for the opposite sex, and information on potential adverse drug reaction (ADR) is lacking. OBJECTIVE: To describe ADR associated with gender transition medication in transgender individuals reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Data from the FAERS database up to June 2023 were examined, focusing on reports of gender transition medication use in the context of gender dysphoria. The ADRs were categorized using the Medical Dictionary for Regulatory Activities at both Preferred Term and System Organ Class (SOC) levels. Descriptive statistics summarized report counts, medication types, indications, and ADR severity. RESULTS: For individuals assigned female at birth undergoing gender transition to male (transgender men), 82 reports (230 ADRs) were analyzed, with an average age of 29.5 years. Transgender hormonal therapy was cited in 72% of reports, predominantly from the United States (67.1%). A striking 88% were categorized as serious ADRs, primarily SOC injury, poisoning, and procedural complications (26.5%), followed by psychiatric disorders (14.8%) and nervous system disorders (12.2%). Among those assigned sex male at birth transitioning to female (transgender women) (81 reports, 237 ADRs), mean age was 33.3 years, with 58% indicating use for gender dysphoria. A significant proportion (53.6%) were serious ADRs, primarily SOC: injury, poisoning, and procedural complications (26.6%). CONCLUSIONS AND RELEVANCE: The FAERS data reveal significant ADRs in transgender individuals using hormone therapy, sometimes unintended for their recipient gender. Population-level studies are crucial to enhance transgender health care. Spontaneous surveillance databases like FAERS illuminate off-label ADRs, urging health care providers to approach hormone therapies with informed caution.

Analysis on the risk of myasthenia gravis related to immune checkpoint inhibitors based on the US FDA Adverse Event Reporting System.

OBJECTIVE: To evaluate the risk of myasthenia gravis (MG) associated with immune checkpoint inhibitors (ICI). METHODS: Adverse event (AE) reports related to MG, myasthenic syndrome, and MG crisis for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab in the US FDA Adverse Event Reporting System (FAERS) from Q1 2004 to Q3 2022 were collected. The proportional reporting odds ratio (PRR) method was used to evaluate the correlation between the six drugs and the three AEs. Statistical significance was defined as having reports ≥3, PRR ≥ 2, and chi-square (χ2 ) ≥ 4. RESULTS: A total of 36, 78, 276, 380, 5, and 53 AE reports were collected for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab, respectively. For myasthenic syndrome, the PRR values reflecting the correlation with the drugs were 27.83 (χ2 = 102.66), 26.20 (χ2 = 235.67), 44.17 (χ2 = 1313.98), 32.09 (χ2 = 1229.54), 21.31 (χ2 = 151.15), and 0 for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab, respectively. For MG, the PRR values reflecting the correlation with the drugs were 24.21 (χ2 = 682.04), 18.34 (χ2 = 900.27), 39.32 (χ2 = 7945.15), 26.93 (χ2 = 6636.45), 14.73 (χ2 = 566.47), and 15.69 (χ2 = 54.77) for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab, respectively. For MG crisis, there were no data for durvalumab, atezolizumab, avelumab, and ipilimumab; the PRR values reflecting the correlation with the drugs were 16.54 (χ2 = 225.23) and 9.20 (χ2 = 119.14) for pembrolizumab and nivolumab, respectively. All six drugs were statistically correlated with their corresponding AEs. CONCLUSIONS: ICI may lead to ICIs-associated MG during therapy. Analysis of FAERS data identified signals for AEs of MG with ICI regimens. Practitioners should consider the factors that may increase the likelihood of MG. The findings support a continued surveillance and risk factor identification.

Chimeric antigen receptor T-cell immunotherapies adverse events reported to FAERS database: focus on cytopenias.

Chimeric antigen receptor (CAR) T-cell therapy presents a promising treatment for hematologic malignancies, displaying high efficacy but not being exempt from toxicity. In this observational study, we assessed adverse events (AEs) reported to the Food and Drug Adverse Event Reporting System (FAERS) including any of the six approved CAR T-cell therapies. A total of 5249 reports mentioning a CAR T-cell as a suspect product were retrieved from the FAERS database, containing a total of 24333 AEs, of which 3236 (13.3%) were cytopenias. The highest number of AEs mentioned by the report was observed for tisagenlecleucel (mean = 6.7), with the lowest for ciltacabtagene (mean = 1.3). Among all reports, hematopoietic leukopenia was the most frequently reported AEs (n = 1386, 5.7%), with hematopoietic erytropenia the least reported (n = 291, 1.2%). Tisagenlecleucel showed a high reporting odds ratio for hematopoietic erythropenia (27.28, 95%CI 14.04-53.00), leukopenia (4.04, 95%CI 3.52-4.64), and thrombocytopenia (4.01, 95%CI 3.19-5.03). Cytopenias represent one of the most frequently reported AEs in FAERS, a CAR T-cell therapy is indicated, with haematopoetic leukopenia being the most common. When comparing different CAR-T cell therapies, the cytopenias' reporting odds ratio was particularly high for tisagenlecleucel, especially in relation to hematopoietic erythropenia.

Acontecimientos adversos en embarazadas con la vacuna tetravalente contra la gripe obtenida de cultivos celulares / Adverse events in pregnant women with the tetravalent influenza vaccine obtained from cell cultures

La vacunación de la gripe en embarazadas muestra una clara relación beneficio/riesgo. En la actualidad se están desarrollando vacunas contra la gripe utilizando nuevas plataformas. Es imprescindible analizar la seguridad de estas nuevas vacunas en este grupo poblacional, infrarrepresentado en los ensayos clínicos. En la temporada 2019-2020 se aconsejó una vacuna obtenida en cultivo celular a las embarazadas en 2comunidades autónomas. Se recogió información de los centros de vacunación y de farmacovigilancia de ambas comunidades. La tasa de notificación de casos de acontecimientos adversos tras la vacunación en embarazadas fue de 4,02/100.000 dosis administradas y, en mujeres de 18 a 64 años no embarazadas, de 5,9/100.000 dosis administradas. La tasa de acontecimientos adversos notificados fue de 8,04 y 17,74, respectivamente. No se notificaron abortos espontáneos, prematuridad ni malformaciones fetales. Este análisis señala la seguridad en embarazadas de la vacuna de la gripe obtenida de cultivos celulares.(AU)

Influenza vaccination in pregnant women shows a clear benefit/risk ratio. Influenza vaccines are currently being developed using new platforms. It is essential to analyze the safety of these new vaccines in this population group, underrepresented in clinical trials. In the 2019-2020 season, a vaccine obtained in cell culture was recommended to pregnant women in 2autonomous communities. Information is collected from the vaccination and pharmacovigilance centers of both communities. The reporting rate of adverse events after vaccination in pregnant women was 4.02/100,000 doses administered, and in non-pregnant women aged 18-64 years it was 5.9/100,000 doses administered. The rate of adverse events reported was 8.04 and 17.74, respectively. No spontaneous abortions, prematurity or fetal malformations were reported. This analysis suggests the safety in pregnant women of the influenza vaccine obtained from cell cultures.(AU)

Reports of Symptoms Associated with Supraventricular Arrhythmias as a Serious Adverse Drug Reaction in the Spanish Pharmacovigilance Database.

This study aimed to determine the type of drugs reported as suspected of causing severe supraventricular arrhythmias from the Spanish Human Pharmacovigilance System database. A total of 1053 reports were analysed, of which 526 (50%) were on men and 516 (49%) were on women. The most affected age group was the over-65s, with 593 reports (56%). Of the 1613 drugs, those belonging to the cardiovascular system (ATC Group C) were the most numerous (414 reports, 26%), with digoxin being the most frequent drug (49 reports, 12%). Other common groups were antiinfectives for systemic use (ATC Group J; 306 reports, 19%), antineoplastic and immunomodulating agents (ATC Group L; 198 reports, 12%), and nervous system drugs (ATC Group N; 185 reports, 11%). The most common supraventricular arrhythmia was atrial fibrillation (561 reports, 51%). Regarding outcomes, 730 (66%) patients recovered, 76 (7%) did not recover, 25 (3%) recovered but with sequelae, and 23 (2%) resulted in death. This study revealed that certain drugs have reported to be associated more frequently to supraventricular arrhythmias as serious adverse reactions, especially in the older population. Proper clinical management and effective strategies to ensure medication appropriateness should always be considered to improve patient safety when prescribing drugs.

Severe immune-mediated hepatitis caused by sindilizumab combined with local radiotherapy: a case report.

A man with diffuse large B-cell lymphoma in the nasal cavity was treated with sindilizumab, an immune checkpoint inhibitor, combined with local radiotherapy for multiple nodules of the left upper arm. After a single administration of sindilizumab and 10 radiotherapy treatments, the patient presented with liver dysfunction. Liver function tests showed that the levels of transaminases had increased abnormally and deteriorated though with intense treatment. His bilirubin level was also increased with obvious yellow staining of the skin and sclera. The patient was considered to have severe immune-mediated hepatitis (IMH) caused by sindilizumab combined with local radiotherapy. His liver function did not improve and he died of organ failure. This is a case of rare liver failure which was considered to be IMH induced by synergistic treatment with immune checkpoint therapy and radiotherapy.

Unknown adverse drug reactions from spontaneous reports in a hospital setting: characterization, follow-up, and contribution to the pharmacovigilance system.

Introduction: Post-marketing identification and report of unknown adverse drug reactions (ADRs) are crucial for patient safety. However, complete information on unknown ADRs seldom is available at the time of spontaneous ADR reports and this can hamper their contribution to the pharmacovigilance system. Methods: In order to characterize the seriousness and outcome of unknown ADRs at the time of report and at follow-up, and analyze their contribution to generate pharmacovigilance regulatory actions, a retrospective observational study of those identified in the spontaneous ADR reports of patients assisted at a hospital (January, 2016-December, 2021) was carried out. Information on demographic, clinical and complementary tests was retrieved from patients' hospital medical records. To evaluate the contribution to pharmacovigilance system we reviewed the European Union SmPCs, the list of the pharmacovigilance signals discussed by the Pharmacovigilance Risk Assessment Committee, and its recommendations reports on safety signals. Results: A total of 15.2% of the spontaneous reported cases during the study contained at least one unknown drug-ADR pair. After exclusions, 295 unknown drug-ADR pairs were included, within them the most frequently affected organs or systems were: skin and subcutaneous tissue (34, 11.5%), hepatobiliary disorders (28, 9.5%), cardiac disorders (28, 9.5%) and central nervous system disorders (27, 9.2%). The most frequent ADRs were pemphigus (7, 2.4%), and cytolytic hepatitis, sudden death, cutaneous vasculitis and fetal growth restriction with 6 (2%) each. Vaccines such as covid-19 and pneumococcus (68, 21.3%), antineoplastics such as paclitaxel, trastuzumab and vincristine (39, 12.2%) and immunosuppressants such as methotrexate and tocilizumab (35, 11%) were the most frequent drug subgroups involved. Sudden death due to hydroxychloroquine alone or in combination (4, 1.4%) and hypertransaminasemia by vincristine (n = 3, 1%) were the most frequent unknown drug-ADR pairs. A total of 269 (91.2%) of them were serious. Complementary tests were performed in 82.7% of unknown-ADR pairs and helped to reinforce their association in 18.3% of them. A total of 18 (6.1%) unknown drug-ADR pairs were evaluated by the EMA, in 8 (2.7%) the information was added to the drug's SmPC and in 1 case the risk prevention material was updated. Conclusion: Identification and follow-up of unknown ADRs can be of great relevance for patient safety and for the enrichment of the pharmacovigilance system.

Assessing adverse drug reaction reports for antidiabetic medications approved by the food and drug administration between 2012 and 2017: a pharmacovigilance study.

Objective: Between 2012 and 2017, the U.S. Food and Drug Administration (FDA) approved 10 antidiabetic indicated therapies. Due to the limited literature on voluntarily reported safety outcomes for recently approved antidiabetic drugs, this study investigated adverse drug reactions (ADRs) reported in the FDA Adverse Event Reporting System (FAERS). Research Design and Methods: A disproportionality analysis of spontaneously reported ADRs was conducted. FAERS reports from January 1, 2012 to March 31, 2022 were compiled, allowing a 5-year buffer following drug approval in 2017. Reporting odds ratios were calculated for the top 10 ADRs, comparing new diabetic agents to the other approved drugs in their therapeutic class. Results: 127,525 reports were identified for newly approved antidiabetic medications listed as the primary suspect (PS). For sodium-glucose co-transporter-2 (SGLT-2) inhibitors, the odds of blood glucose increased, nausea, and dizziness being reported was greater for empagliflozin. Dapagliflozin was associated with greater reports of weight decreased. Canagliflozin was found to have a disproportionally higher number of reports for diabetic ketoacidosis, toe amputation, acute kidney injury, fungal infections, and osteomyelitis. Assessing glucagon-like peptide-1 (GLP-1) receptor agonists, dulaglutide and semaglutide were associated with greater reports of gastrointestinal adverse drug reactions. Exenatide was disproportionally associated with injection site reactions and pancreatic carcinoma reports. Conclusion: Pharmacovigilance studies utilizing a large publicly available dataset allow an essential opportunity to evaluate the safety profile of antidiabetic drugs utilized in clinical practice. Additional research is needed to evaluate these reported safety concerns for recently approved antidiabetic medications to determine causality.

Adverse drug reactions reported for antidiabetic medications Introduction: This study investigated the trends in voluntary reporting of adverse drug reactions for recently approved antidiabetic medications. Methods: Data from the FDA Adverse Events Reporting System were evaluated. The top 10 adverse drug reactions were compared between antidiabetic medications in the same therapeutic class. Results: We identified 127,525 adverse drug reaction reports for the newer approved antidiabetic medications. For SGLT-2 inhibitors, empagliflozin was associated with greater reports of blood glucose increase, nausea, and dizziness; weight decreased was reported more often for dapagliflozin; and diabetic ketoacidosis, toe amputation, acute kidney injury, fungal infections, and osteomyelitis were reported more commonly for canagliflozin. Assessing GLP-1 receptor agonists, the odds of gastrointestinal adverse drug reactions being reported was greater for dulaglutide and semaglutide. Exenatide was disproportionally associated with injection site reactions and pancreatic carcinoma reports. Conclusion: Medication safety studies using a large publicly available dataset allows an essential opportunity to evaluate the safety profile of antidiabetic drugs in the real-world setting. Additional research is needed to determine if the reported safety concerns for recently approved antidiabetic medications to determine causality.

Fluoropyrimidine usage in cases with hyperammonemia: real-world data study using the Japanese Adverse Drug Event Report (JADER) database.

PURPOSE: Fluoropyrimidines are anticancer drugs and can cause hyperammonemia both intravenously and orally. Renal dysfunction may interact with fluoropyrimidine to cause hyperammonemia. We performed quantitative analyses of hyperammonemia using a spontaneous report database to examine the frequency of intravenously and orally administered fluoropyrimidine, the reported frequency of fluoropyrimidine-related regimens, and fluoropyrimidine's interactions with chronic kidney disease (CKD). METHODS: This study used data collected between April 2004 and March 2020 from the Japanese Adverse Drug Event Report database. The reporting odds ratio (ROR) of hyperammonemia was calculated for each fluoropyrimidine drug and was adjusted for age and sex. Heatmaps depicting the use of anticancer agents in patients with hyperammonemia were drawn. The interactions between CKD and the fluoropyrimidines were also calculated. These analyses were performed using multiple logistic regression. RESULTS: Hyperammonemia was observed in 861 of the 641,736 adverse events reports. Fluorouracil was the most frequent drug associated with hyperammonemia (389 cases). The ROR of hyperammonemia was 32.5 (95% CI 28.3-37.2) for intravenously administered fluorouracil, 4.7 (95% CI 3.3-6.6) for orally administered capecitabine, 1.9 (95% CI 0.87-4.3) for tegafur/uracil, and 2.2 (95% CI 1.5-3.2) for orally administered tegafur/gimeracil/oteracil. Calcium levofolinate, oxaliplatin, bevacizumab, and irinotecan were the most frequently reported agents in cases of hyperammonemia with intravenously administered fluorouracil. The coefficient of the interaction term between CKD and fluoropyrimidines was 1.12 (95% CI 1.09-1.16). CONCLUSION: Hyperammonemia cases were more likely to be reported with intravenous fluorouracil than orally administered fluoropyrimidines. Fluoropyrimidines might interact with CKD in hyperammonemia cases.

Role of spontaneous reporting in investigating the relationship between mRNA COVID-19 vaccines and myocarditis: The French perspective.

AIM OF THE STUDY: Post-mRNA coronavirus diseases 2019 (COVID-19) vaccines myocarditis emerged as a rare adverse effect, particularly in adolescents and young adults, and was labeled as such for both vaccines in the summer of 2021. This study aims to summarize the timeline and process of signal detection, substantiation, and quantification of myocarditis cases related to mRNA vaccines in France. METHODS: The intensive monitoring plan for COVID-19 vaccine safety was based on case-by-case analysis of all cases collected in the French spontaneous reporting database (Base nationale de pharmacovigilance, BNPV). Cases were evaluated by drug safety medical professionals and discussed at a national level for signal detection purposes. Reported cases were compared to the number of vaccine-exposed persons up to September 30th, 2021. Reporting rates (Rr) of myocarditis per 100,000 injections were calculated and stratified according to age, gender, and injection rank of BNT162b2 and mRNA-1273 vaccines. Poisson distribution was used to compute Rrs 95% Confidence Interval (95% CI). RESULTS: The case-by-case analysis detected a possible cluster of myocarditis in April 2021 (5 cases, 4 after the 2nd injection). In June 2021, the signal was substantiated with 12 cases (9 related to BNT162b2, and 3 to mRNA-1273). As of September 2021, almost 73 million BNT162b2 and 10 million mRNA-1273 doses had been injected. The Rr per 100,000 injections was 0.5 (0.5-0.6) for BNT162b2 and 1.1 (95% CI 0.9-1.3) for mRNA-1273. The difference among vaccines was more pronounced after the second injection, particularly in men aged 18-24 years (4.3 [3.4-5.5] for BNT162b2 vs. 13.9 [9.2-20.1] for mRNA-1273) and aged 25-29 years (1.9 [1.2-2.9] vs. 7.0 [3.4-12.9]). CONCLUSION: The study highlighted the role of the spontaneous reporting system in the detection, assessment, and quantification of myocarditis related to m-RNA vaccines. It suggested from September 2021 that mRNA-1273 was reasonably related to a higher risk of myocarditis than BNT162b2 in people under 30, particularly after the second injection.

Signal detection of COVID-19 vaccines adverse events using spontaneous reports from South Korea.

PURPOSE: Studies on the detection of COVID-19 vaccine signals in South Korea are insufficient. Therefore, to investigate adverse events (AEs) that might be associated with COVID-19 vaccines, signals were detected using spontaneous reports from South Korea. We compared the signals with the vaccine insert lists of the regulators in the four countries. METHODS: Spontaneous reports from 62 sites were collected by the National Medical Center between January 2013 and May 2022. A descriptive analysis of AEs associated with COVID-19 vaccines (Pfizer, Moderna, AstraZeneca, and Janssen) was performed, and the proportional reporting ratio, reporting odds ratio, and information component were calculated. We performed five analyses, with five cases and one control group. RESULTS: During the study period, 68 355 cases were reported, of which 12 485 were COVID-19 vaccine AEs. Injection site pain (2198 cases, 17.6%), myalgia (1552 cases, 12.4%), headache (1145 cases, 9.2%), pyrexia (1003 cases, 8.0%), and fatigue (735 cases, 5.9%) were frequently reported. When comparing all COVID-19 vaccines with other viral vaccines, 20 signals were detected, of which cachexia, dyspepsia, abdominal discomfort, and mood swings were not listed on the vaccine inserts in all four countries. Overall, 20, 17, 29, and 9 signals were detected in vaccines developed by Pfizer, Moderna, AstraZeneca, and Janssen, respectively. CONCLUSIONS: Based on a disproportionate analysis of COVID-19 vaccine AEs using spontaneous reports from South Korea, different signals were detected for each vaccine manufacturer.

Identification and Characterization of Preventable Adverse Drug Events in Family Medicine Clinics from Central Saudi Arabia.

Background: Medication errors can result in adverse drug events (ADEs) and cause considerable patient harm. Limited data are available from Saudi Arabia and the Middle East regarding the prevalence of preventable adverse drug events (pADEs) in primary care settings. Objectives: To estimate the period prevalence of pADEs and assess the medication error severity in primary care setting in Saudi Arabia. Methods: This retrospective study is a continuation of a previous study where 117 of 2000 adult patients managed at the Family Medicine clinics of King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, were identified to have had least one medication error in the past 15 months. The electronic health records of these 117 patients were analyzed for a 3-month post-medication error period to explore the presence of pADE. Medication errors were categorized according to the National Coordinating Council for Medication Error Reporting and Prevention index (NCC MERP) and the occurrence of pADE was assessed using the NCC MERP scheme. Results: Of the included 117 patients, 9 (7.7% [95% confidence interval (CI): 2.79-12.59]) experienced pADE (Category E), while 108 (92.3% [95% CI: 87.97-98.35]) did not (Category C). All patients who experienced pADE were using over-the-counter medications and were on polypharmacy. Outcomes 2a and 2b (asthma and ß-blocker) accounted for two and four cases, respectively, while Outcomes 6 (warfarin and international normalized ratio), 7 (lithium and lithium level), 16 (new oral anti-coagulant or warfarin and antiplatelet), and 17 (acetylsalicylic acid [aspirin] and antiplatelet) each accounted for one case. Conclusions: This study provides the period prevalence of patients with pADEs from Family Medicine clinics at a major tertiary hospital of Saudi Arabia, and highlights the need for a multicenter study of clinically important medication errors at the prescribing and monitoring stages for the development of quality improvement programs.

Ototoxicity prognostic models in adult and pediatric cancer patients: a rapid review.

PURPOSE: A cornerstone of treatment for many cancers is the administration of platinum-based chemotherapies and/or ionizing radiation, which can be ototoxic. An accurate ototoxicity risk assessment would be useful for counseling, treatment planning, and survivorship follow-up in patients with cancer. METHODS: This systematic review evaluated the literature on predictive models for estimating a patient's risk for chemotherapy-related auditory injury to accelerate development of computational approaches for the clinical management of ototoxicity in cancer patients. Of the 1195 articles identified in a PubMed search from 2010 forward, 15 studies met inclusion for the review. CONCLUSIONS: All but 1 study used an abstraction of the audiogram as a modeled outcome; however, specific outcome measures varied. Consistently used predictors were age, baseline hearing, cumulative cisplatin dose, and radiation dose to the cochlea. Just 5 studies were judged to have an overall low risk of bias. Future studies should attempt to minimize bias by following statistical best practices including not selecting multivariate predictors based on univariate analysis, validation in independent cohorts, and clearly reporting the management of missing and censored data. Future modeling efforts should adopt a transdisciplinary approach to define a unified set of clinical, treatment, and/or genetic risk factors. Creating a flexible model that uses a common set of predictors to forecast the full post-treatment audiogram may accelerate work in this area. Such a model could be adapted for use in counseling, treatment planning, and follow-up by audiologists and oncologists and could be incorporated into ototoxicity genetic association studies as well as clinical trials investigating otoprotective agents. IMPLICATIONS FOR CANCER SURVIVORS: Improvements in the ability to model post-treatment hearing loss can help to improve patient quality of life following cancer care. The improvements advocated for in this review should allow for the acceleration of advancements in modeling the auditory impact of these treatments to support treatment planning and patient counseling during and after care.

Patient involvement in pharmacovigilance: determinants and evolution of reporting from 2011 to 2020 in France.

INTRODUCTION: Because patients and patient organizations want to strengthen their role in the care pathway and drug evaluation and in order to improve pharmacovigilance activities, European competent authorities implemented regulations to allow direct reporting of adverse drug reactions related to medicinal products by patients in 2012. OBJECTIVES: To describe evolution and analyze determinants of patient reporting activity in France in order to assess patient involvement in pharmacovigilance. METHOD: Using the French national pharmacovigilance database, univariate and multivariate analyses were performed to compare the characteristics of adverse drug reaction (ADR) reports from patients and healthcare professionals (HCP) between 2011 and 2020. The relationship between regional patient ADR report activity and regional care provision and socio-professional characteristics was analyzed using the principal component analysis. RESULTS: A significant and higher increase in ADR reports over time from patients (r = 0.89, p < 0.001) compared to HCP (r = 0.27, p = 0.002) has been observed. Patient ADR report activities compared to HCP concerned more women (80% vs. 55%, p < 0.001), younger age classes (p < 0.001), reporting through web portal (83% vs. 17%, p < 0.001), and less serious events (26% vs. 63%, p < 0.001). In the principal component analysis, regional patient reporting activity was related to socio-professional categories, age classes, and densities of hospital beds and physicians. CONCLUSION: Our results confirm an increasing involvement of patients in ADR report activities. The determinants of patient reporting activities are not only related to drug and medical factors but also to social factors. Digital tools may also play a role in health democracy in pharmacovigilance.