Real-World Monitoring of COVID-19 Vaccines: An Industry Expert View on the Successes, Challenges, and Future Opportunities.

Pharmacovigilance leaders from major vaccine developers describe the learnings from the coronavirus disease 2019 (COVID-19) pandemic in the area of pharmacovigilance and pharmacoepidemiology. The authors aim to raise awareness of the co-operation among vaccine developers, highlight common challenges, advocate for solutions, and propose recommendations for the future in the areas of real-world safety and effectiveness, safety reporting and evaluation, and regulatory submissions. To enable timely evaluation of real-world safety and effectiveness, multi-sponsor study platforms were implemented, resulting in quicker recruitment over wide geographical areas. Future gains could be derived by developing geographically flexible, common protocols and/or joint company-sponsored studies for multiple vaccines and a collective strategy to build low/middle-income country (LMIC) sentinel sites. Safety reporting, signal detection and evaluation was particularly challenging given the unprecedented number of adverse events reported. New methods were required to manage increased report volume while maintaining the ability to quickly identify and respond to new data that could impact the benefit-risk profile of each vaccine. Worldwide health authority submissions, requests for information and differing regulatory requirements imposed significant burden on regulators and industry. Industry consensus on the safety reporting requirements and joint meetings with regulatory authorities markedly reduced this burden for all stakeholders. The most impactful innovations should be undertaken rapidly and expanded to other vaccines and therapeutics, with a multi-stakeholder approach. The authors of this paper make future recommendations and have launched an initiative named BeCOME (Beyond COVID Monitoring Excellence) with a focus on actions in each of the highlighted areas.

Improving the Safety of Medicines via Digital Technology: An Assessment of the Scope and Quality of Risk Minimization Websites in the United States and United Kingdom.

INTRODUCTION: EHealth holds tremendous promise for enhancing drug safety initiatives known as risk minimization programs. Little is known, however, regarding the scope and quality of existing risk minimization websites. METHODS: Two publicly accessible repositories, REMS@FDA [1] and Electronic Medicines Compendium [2], were reviewed to identify all regulatorily approved risk minimization programs in the United States (US) and United Kingdom (UK) with websites. Website quality was evaluated using the Enlight Quality Assessment tool, a psychometrically validated instrument that addresses seven quality domains. RESULTS: Ninety-three websites were identified: 59 for healthcare professionals (7 UK/52 US), and 34 for patients (5 UK/29 US). The websites functioned chiefly as archives for electronic copies of educational materials; a subset (31/93) had additional features. Mean quality ratings for Usability (mean 4.70, SD 0.59), Visual Design (mean 4.03, SD 0.87) and Content (mean 4.31, SD 0.82) were good. General Subjective Evaluation was fair (mean 3.15, SD 1.21). Mean scores for Therapeutic Alliance and Therapeutic Persuasiveness were poor (mean 2.62, SD 1.47; and mean 2.50, SD 1.48, respectively); those for User Engagement were very poor (mean 2.25, SD 1.03). No differences were found by target audience but several were identified based on region. CONCLUSIONS: Risk minimization websites are easy to navigate and well organized. Few, however, incorporate eHealth design elements that facilitate user engagement, build therapeutic alliance and exert therapeutic persuasiveness. Such elements can enhance program uptake and effectiveness. Results highlight opportunities for improving the quality of risk minimization websites and their ability to bridge pharmaceutical and healthcare systems.

A risk minimization program is a type of drug safety measure to ensure that a medicine's benefits outweigh its risks. Electronic versions of these risk minimization programs (websites) offer new ways to reach and educate patients and healthcare professionals. We conducted a study to examine the quality of these websites. We reviewed all approved risk minimization programs in the United States (US) and the United Kingdom (UK) using two publicly available repositories, REMS@FDA and Electronic Medicines Compendium, to identify risk minimization websites. We assessed website quality using the Enlight Quality Assessment tool. We found 93 websites: 59 for healthcare professionals (7 UK/52 US) and 34 for patients (5 UK/29 US). Our analysis showed that the websites were well organized and easy to search. Few, however, used specific electronic design elements that can promote trust in and engagement with the content of the website, and can encourage users to follow the recommended actions for safe and appropriate use of the medicine. In conclusion, there are multiple ways that the design of risk minimization websites could be improved in order to make them more effective as drug safety measures.

The RIMES Statement: A Checklist to Assess the Quality of Studies Evaluating Risk Minimization Programs for Medicinal Products.

INTRODUCTION: Pharmaceutical risk minimization programs involve interventions designed to support safe and appropriate use of medicines. Currently, information regarding the evaluation of these programs is not publicly reported in a standardized and transparent manner. To address this gap, we developed and piloted a quality reporting checklist entitled the Reporting recommendations Intended for pharmaceutical risk Minimization Evaluation Studies (RIMES). METHODS: Checklist development was guided by three sources: (1) a theoretical framework derived from program theory and process evaluation; (2) public health intervention design and evaluation principles; and (3) a review of existing quality reporting checklists. Two raters independently reviewed 10 recently published (2012-2016) risk minimization program evaluation studies using the proposed checklist. Inter-rater reliability of the checklist was assessed using Cohen's Kappa and Gwet's AC1. RESULTS: A 43-item checklist was generated. Results indicated substantial inter-rater reliability overall (κ = 0.65, AC1 = 0.65) and for three (key information, design and evaluation) of the four subscales (κ ≥ 0.64, AC1 ≥ 0.64). The fourth subscale (implementation) showed low reliability based on Cohen's Kappa, but substantial reliability based on the AC1 (κ = 0.17, AC1 = 0.61). CONCLUSIONS: The RIMES statement augments relevant elements from existing quality reporting guidelines with items that address aspects of intervention design, implementation and evaluation specific to pharmaceutical risk minimization programs. Our results show that the RIMES statement reliably measures key dimensions of reporting quality. This tailored checklist is an important first step in improving the reporting quality of risk minimization evaluation studies and may ultimately help to improve the quality of these interventions themselves.

Methodological gaps in the assessment of risk minimization interventions: a systematic review.

INTRODUCTION: Since the introduction of therapeutic risk management regulatory guidance, an increase in the number of risk minimization interventions (RMIs) published in the literature has been observed. Methods used to evaluate their effectiveness remain, however, poorly examined. OBJECTIVE: This paper aimed to conduct a literature review on the methods of evaluation of effectiveness of RMIs and to identify methodological gaps. METHODS: The search was conducted using MEDLINE and Embase between 1 January 2000 and 31 December 2010, and updated on 1 April 2013. The following characteristics were extracted from each study: target population for the RMI, target population for the assessment of effectiveness, study design, data sources, and effectiveness outcome(s). RESULTS: A total of 188 unique RMIs were identified in the literature, of which effectiveness was evaluated in only 65 (34.6%) at the time of publication. The largest proportion of studies reviewed (n = 49, 75.4%) attempted to evaluate changes in behavior through prescribing or laboratory test practices. One quarter of studies evaluated the effect of RMIs on the occurrence of adverse events. Only a minority of studies used robust designs, such as randomized controlled trials (n = 6, 9.2%) or a quasi-experimental design with a parallel comparison group (n = 8, 12.3%). CONCLUSION: Lack of robust methodological design used in published studies on RMI effectiveness evaluation is an important methodological gap in the evaluation of RMI effectiveness. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

Menstrual and reproductive risk factors and risk for gastric adenocarcinoma in women: findings from the canadian national enhanced cancer surveillance system.

PURPOSE: The role of menstrual and reproductive risk factors for gastric cancer has not been well studied. METHODS: This population-based case-control study included 326 women aged 20 to 74 years with gastric adenocarcinoma. Controls were 326 women frequency matched on age. Data for reproductive and/or hormonal exposure and gastric cancer risk factors were captured through self-administered questionnaire. RESULTS: Later age at menarche was associated with increased risk for adenocarcinoma compared with menarche onset at younger than 13 years of age (13 to 14 years: odds ratio [OR], 1.45; 95% confidence interval [CI], 1.00-2.10; > or =15 years: OR, 1.93; 95% CI, 1.19-3.13). Compared with premenopause, natural menopause was associated with increased risk for adenocarcinoma (OR, 1.99; 95% CI, 0.98-4.05). Compared with nulliparity, 4 or more births were associated with decreased risk for gastric cancer, as was being pregnant for 5 months or longer if the first pregnancy occurred at younger than 24 years (OR, 0.55; 95% CI, 0.31-0.96) or 25 years or older (OR, 0.67; 95% CI, 0.38-1.18). Oral contraceptives and hormone replacement therapy were associated with a non-statistically significant decreased risk. CONCLUSION: These findings suggest that hormonal factors associated with greater exposure to estrogen and/or progesterone may be associated with decreased risk for gastric cancer.

Psychiatric disorders and use of mental health services by Ontario women.

OBJECTIVES: To describe the lifetime prevalence of selected psychiatric disorders in Ontario women and to compare these estimates with use of mental health resources. METHODS: We obtained data from a survey of 3062 Ontario women, aged 25 to 74 years, who participated in the Women's Health Study. A 5-item scale assessed lifetime prevalence of 5 psychiatric disorders (anxiety, depression, posttraumatic stress disorder [PTSD], obsessive-compulsive disorder [OCD], and anorexia [AN] or bulimia [BN]). We assessed use of mental health services by comorbidity. We employed stratified random sampling to select study subjects. Prevalence estimates were weighted and 95%CIs were obtained using Taylor linearization techniques (1). RESULTS: Nearly 30% of those surveyed reported at least 1 of the disorders studied. The most common were depression (27%) and anxiety (21%). Lifetime prevalence of PTSD, OCD, and AN or BN were 10.7%, 6.1%, and 3.9%, respectively. Successively younger birth cohorts displayed an increase in prevalence and a decrease in onset-age for all disorders. "Ever" use of mental health services was higher for women with 3 or more comorbid disorders (65%) than for those with no disorder (9.8%), or only 1 disorder (51.4%). CONCLUSIONS: The results of this study highlight the need to conduct more research into the reasons for the low rates of professional service use, especially for women with high comorbidity. They also highlight the need to understand the phenomenon underlying the possibly increasing rates of disorders in younger birth cohorts, so that outreach strategies can be modified to accommodate differences in younger women.