PP299 A Framework And Analysis Assessing The Impact Of Patient-Centered Outcome Evidence In HTA Appraisals

IntroductionThe importance of patient-centered outcome (PCO) evidence is increasingly recognized, but its inclusion in Health Technology Assessment (HTA) submissions remains inconsistent. We explored the impact of PCO evidence on HTA decision-making.MethodsA framework was developed to assess the impact of PCO evidence (excluding EQ-5D) on HTA appraisals. An impact rating was determined by reviewing company, committee and Evidence Review Group (ERG) opinion. This was applied to publicly available appraisal documents (National Institute for Health and Care Excellence [NICE]: 8; Scottish Medicines Consortium [SMC]: 2) in a pilot study. The framework was then refined and applied to a larger dataset.ResultsPCO evidence had ‘substantial impact’ in 3/8 NICE and 1/2 SMC appraisals, and ‘some impact’ in those remaining. PCO evidence informed the cost-effectiveness model in 2/8 NICE and 1/2 SMC submissions, and was considered superior to EQ-5D evidence in one NICE and one SMC submission. The ERG considered PCO evidence relevant to decision-making in 5/8 NICE appraisals. PCO evidence was mentioned in guidance for 7/10 appraisals (deemed relevant in 5/10). In one assessment, committee comments were notably more favorable than ERG comments. Larger dataset analysis results provided further insights to the pilot study.ConclusionsThe framework allows a systematic approach to evaluating the impact of PCO evidence on HTA appraisals.BL, AP, DGB and NY are employees of Symmetron Ltd, which received funding from Pfizer UK in connection with the development of this manuscript. KH, HT, SLC and JB are employees of Pfizer UK. This study was sponsored by Pfizer UK.

A Quantitative Benefit–Risk Analysis of ChAdOx1 nCoV-19 Vaccine among People under 60 in Italy

The Oxford-AstraZeneca ChAdOx1 nCoV-19 is a vaccine against the COVID-19 infection that was granted a conditional marketing authorization by the European Commission in January 2021. However, following a report from the Pharmacovigilance Risk Assessment Committee (PRAC) of European Medicines Agency, which reported an association with thrombo-embolic events (TEE), in particular disseminated intravascular coagulation (DIC) and cerebral venous sinus thrombosis (CVST), many European countries either limited it to individuals older than 55–60 years or suspended its use. We used publicly available data to carry out a quantitative benefit–risk analysis of the vaccine among people under 60 in Italy. Specifically, we used data from PRAC, Eudravigilance and ECDC to estimate the excess number of deaths for TEE, DIC and CVST expected in vaccine users, stratified by age groups. We then used data from the National Institute of Health to calculate age-specific COVID-19 mortality rates in Italy. Preventable deaths were calculated assuming a 72% vaccine efficacy over an eight-month period. Finally, the benefit–risk ratio of ChAdOx1 nCoV-19 vaccination was calculated as the ratio of preventable COVID-19 deaths to vaccine-related deaths, using Monte-Carlo simulations. We found that among subjects aged 20–29 years the benefit–risk (B-R) ratio was not clearly favorable (0.70; 95% Uncertainty Interval (UI): 0.27–2.11). However, in the other age groups the benefits of vaccination largely exceeded the risks (for age 30–49, B-R ratio: 22.9: 95%UI: 10.1–186.4). For age 50–59, B-R ratio: 1577.1: 95%UI: 1176.9–2121.5). Although many countries have limited the use of the ChAdOx1 nCoV-19 vaccine, the benefits of using this vaccine clearly outweigh the risks in people older than 30 years. Study limitations included risk of underreporting and that we did not provide age-specific estimates. The use of this vaccine should be a strategic and fundamental part of the immunization campaign considering its safety and efficacy in preventing COVID-19 and its complications.

Analysis of Thrombotic Adverse Reactions of COVID-19 AstraZeneca Vaccine Reported to EudraVigilance Database

The development of safe, effective, affordable vaccines against COVID-19 remains the cornerstone to mitigating this pandemic. Early in December 2020, multiple research groups had designed potential vaccines. From 11 March 2021, several European countries temporarily suspended the use of the Oxford–AstraZeneca vaccine amid reports of blood clot events and the death of a vaccinated person, despite the European Medicines Agency (EMA) and the World Health Organization’s assurance that there was no indication that vaccination was linked. This study aimed to identify and analyse the thrombotic adverse reactions associated with the Oxford–AstraZeneca vaccine. This was a retrospective descriptive study using spontaneous reports submitted to the EudraVigilance database in the period from 17 February to 12 March 2021. There were 54,571 adverse reaction reports, of which 28 were associated with thrombotic adverse reactions. Three fatalities were related to pulmonary embolism; one fatality to thrombosis. With 17 million people having had the AstraZeneca vaccine, these are extremely rare events The EMA’s Pharmacovigilance Risk Assessment Committee (18 March 2021) concluded that the vaccine was safe, effective and the benefits outweighed the risks. Conducting further analyses based on more detailed thrombotic adverse event reports, including patients’ characteristics and comorbidities, may enable assessment of the causality with higher specificity.

Analysis of Thrombotic Adverse Reactions of COVID-19 AstraZeneca Vaccine reported to EudraVigilance database

The development of safe, effective, affordable vaccines against COVID-19 remains the cornerstone to mitigating this pandemic. Early December 2020, multiple research groups had designed potential vaccines. From 11 March 2021, several European countries temporarily suspended the use of the Oxford-AstraZeneca vaccine amid reports of blood clot events and death of a vaccinated person, despite the European Medicines Agency and the World Health Organization assurance that there was no indication that vaccination was linked. This study aimed to identify and analyse the thrombotic adverse reactions associated with Oxford-AstraZeneca vaccine. This was a retrospective descriptive study using spontaneous reports submitted to the EudraVigilance database in the period from 17 February to 12 March 2021. There were 54,571 adverse reaction reports of which 28 were associated with thrombotic adverse reactions. Three fatalities were related to Pulmonary Embolism and 1 fatality to Thrombosis. With 17 million people having had the AstraZeneca vaccine, these are extremely rare events. The EMA Pharmacovigilance Risk Assessment Committee (18 March 2021) concluded that the vaccine was safe, effective and the benefits outweighed the risks. Conducting further analyses based on more detailed thrombotic adverse event reports, including patients characteristics and comorbidities, may enable assessment of the causality with higher specificity.

Implications of the Pharmacovigilance Risk Assessment Committee recommendations for the treatment of genitourinary syndrome

The European Medicines Agency's Pharmacovigilance Risk Assessment Committee has issued statements regarding limiting the use of high-dose oestradiol creams by women experiencing the genitourinary syndrome of menopause, and such statements carry much medicolegal weight. Although a low dose is most often used, some clinicians opt to use higher dose creams with close monitoring of the patient. The committee should publish the evidence behind these statements or amend its official position.

Medical education in times of COVID – 19: an experience at Faculdade Pernambucana da Saúde

Objectives: to describe and discuss interventions and strategies carried out at Faculdade Pernambucana de Saúde (FPS) during the COVID-19 pandemic to mitigate impairment in learning and preserve students, tutors, and staff’s health. Experience report: the teaching methodology used by FPS is problem-based learning, which greatly facilitated the non-discontinuity of theoretical activities carried out in-person in tutorial sessions involving a tutor and 10 to 12 students. This format was transferred to Webex Meetings rooms and held remotely. Practical laboratory activities were suspended and resumed when allowed in July. The teaching outpatient activities (third and fourth year) were suspended and resumed in August. Two years of internship were interrupted for 30 days (fifth year) and for 15 days (sixth year). External activities of practices in primary care were also suspended and resumed gradually. All assessments and activities that required face-to-face meetings, integrations, scientific initiation program orientations, collegiate meetings, meetings of the self-assessment committee were and are being carried out remotely. Conclusions: we believe that we were able to mitigate impairment in students' learning without compromising the conclusion of the school year that was facilitated by Problem Based Learning method.

Pharmacovigilance: procedures for uniform assessment of periodic safety update reports and their implementation in national settings. Focus on analgesics

Pharmacovigilance activities are of vital importance for ensuring effective and safe medicinal products. In order to clarify to which extent marketing authorisation holders (MAHs) meet the requirements of the Law and the Directives related to this activities, we conducted a systematic search among the procedures submitted to the Bulgarian Drug Agency (BDA) related to the implementation of the decisions of the Pharmacovigilance Committee and the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) for a period of 6 years. The results of the study showed significant discrepancies between regulatory requirements and the behavior of the MAH at the national level. This could be a serious problem, as inadequate or late implementations of the PRAC (Pharmacovigilance Risk Assessment Committee)/CMDh/EC recommendations can lead to untimely informing of healthcare professionals and patients about potential safety concerns and risks related to the use of medicinal products.