Patient-reported reactogenicity and safety of COVID-19 vaccinations vs. comparator vaccinations: a comparative observational cohort study.

BACKGROUND: In the course of the SARS-CoV-2 pandemic, multiple vaccines were developed. Little was known about reactogenicity and safety in comparison to established vaccines, e.g. influenza, pneumococcus, or herpes zoster. Therefore, the present study aimed to compare self-reported side effects in persons vaccinated against SARS-CoV-2 with the incidence of side effects in persons receiving one of the established vaccines. METHODS: A longitudinal observational study was conducted over a total of 124 days using web-based surveys. Persons receiving either a vaccination against SARS-CoV-2 or one of the established vaccines (comparator group) were included. In the first questionnaire (short-term survey), 2 weeks after vaccination, mainly local and systemic complaints were evaluated. The long-term survey (42 days after vaccination) and follow-up survey (124 weeks after vaccination) focused on medical consultations for any reason. Multivariate analyses were conducted to determine the influence of the vaccine type (SARS-CoV-2 vs. comparator) and demographic factors. RESULTS: In total, data from 16,636 participants were included. Self-reported reactogenicity was lowest in the comparator group (53.2%) and highest in the ChAdOx1 group (85.3%). Local reactions were reported most frequently after mRNA-1273 (73.9%) and systemic reactions mainly after vector-based vaccines (79.8%). Almost all SARS-CoV-2 vaccines showed increased odds of reporting local or systemic reactions. Approximately equal proportions of participants reported medical consultations. None in the comparator group suspected a link to vaccination, while this was true for just over one in 10 in the mRNA-1273 group. The multivariate analysis showed that people with SARS-CoV-2 vaccination were not more likely to report medical consultations; patients who had received a regimen with at least one ChAdOx1 were even less likely to report medical consultations. Younger age, female gender and higher comorbidity were mostly associated with higher odds of medical consultations. CONCLUSION: The rate of adverse reactions after established vaccinations was roughly comparable to previous studies. Two weeks after vaccination, participants in the SARS-CoV-2 vaccination group reported more local and systemic local reactions than participants in the comparator group. In the further course, however, there were no higher odds of medical consultations in either of the two groups. Thus, altogether, we assume comparable safety. TRIAL REGISTRATION: DRKS-ID DRKS00025881 and DRKS-ID DRKS00025373.

Reactogenicity and safety of COVID-19 primary immunisation and booster vaccination regimens: a comparative observational cohort study.

BACKGROUND: Since the beginning of the COVID-19 vaccination campaigns, recommendations regarding the vaccination have been very dynamic. Although the safety and efficacy of different vaccines have been analysed, data were scarce for vaccine regimens combining different vaccines. We therefore aimed to evaluate and compare the perceived reactogenicity and need for medical consultation after the most frequently applied homologous and heterologous COVID-19 vaccination regimens. METHODS: In an observational cohort study, reactogenicity and safety were assessed within a maximum follow-up time of 124 days using web-based surveys. Reactogenicity was assessed for different vaccination regimens 2 weeks after a vaccination (short-term survey). The following surveys, long-term and follow-up surveys, focused on the utilisation of medical services, including those that were not suspected to be vaccine-related. RESULTS: Data of 17,269 participants were analysed. The least local reactions were seen after a ChAdOx1 - ChAdOx1 regimen (32.6%, 95% CI [28.2, 37.2]) and the most after the first dose with mRNA-1273 (73.9%, 95% CI [70.5, 77.2]). Systemic reactions were least frequent in participants with a BNT162b2 booster after a homologous primary immunisation with ChAdOx1 (42.9%, 95% CI [32.1, 54.1]) and most frequent after a ChAdOx1 - mRNA-1273 (85.5%, 95% CI [82.9, 87.8]) and mRNA-1273/mRNA-1273 regimen (85.1%, 95% CI [83.2, 87.0]). In the short-term survey, the most common consequences were medication intake and sick leave (after local reactions 0% to 9.9%; after systemic reactions 4.5% to 37.9%). In the long-term and follow-up surveys, between 8.2 and 30.9% of participants reported consulting a doctor and between 0% and 5.4% seeking hospital care. The regression analyses 124 days after the first and after the third dose showed that the odds for reporting medical consultation were comparable between the vaccination regimens. CONCLUSIONS: Our analysis revealed differences in reactogenicity between the COVID-19 vaccines and vaccination regimens in Germany. The lowest reactogenicity as reported by participants was seen with BNT162b2, especially in homologous vaccination regimens. However, in all vaccination regimens reactogenicity rarely led to medical consultations. Small differences in seeking any medical consultation after 6 weeks diminished during the follow-up period. In the end, none of the vaccination regimens was associated with a higher risk for medical consultation. TRIAL REGISTRATION: DRKS DRKS00025881 ( https://drks.de/search/de/trial/DRKS00025373 ). Registered on 14 October 2021. DRKS DRKS00025373 ( https://drks.de/search/de/trial/DRKS00025881 ). Registered on 21 May 2021. Registered retrospectively.

Physicians' assessment of the Bavarian drug-expenditure control system: a qualitative study.

BACKGROUND: In 2014 a new system for drug expenditures, the Wirkstoffvereinbarung (WSV, English: Active substance agreement) was implemented in Bavaria. In pre-defined indication groups, economic prescription of medications shall be enabled based on the selection, quantity, and proportion of an individual drug. Ambulatory care physicians receive quarterly trend reports on their prescribing behavior. This study examines physicians' perceptions of the WSV. METHODS: Qualitative interviews (n = 20) and seven focus groups (n = 36) were conducted with ambulatory care physicians (e.g. general practitioners, cardiologists, pulmonologists). The methodology followed Qualitative Content Analysis. RESULTS: Physicians generally accepted the necessity of prescribing economically. The majority of them rated the WSV positively and better than the previous system. As an improvement, they especially named timely feedback in form of easily understandable trend reports, encouraging self-reflection as well as allowing early control options. Problems perceived were drug discount contracts that were strongly criticized as leading to patients mixing up medications. Some perceived constraints of therapeutic freedom. CONCLUSIONS: The implementation of the WSV is mostly viewed positively by physicians. The restrictions of therapeutic freedom partially perceived might be met by improved information on the reasons why some drugs are rated as less economical than others. TRIAL REGISTRATION NUMBER: Main ID: DRKS00019820 (German Register of Clinical Studies and World Health Organization).

Reactogenicity after heterologous and homologous COVID-19 prime-boost vaccination regimens: descriptive interim results of a comparative observational cohort study.

BACKGROUND: Due to safety signals after vaccination with COVID-19 vector vaccines, several states recommended to complete the primary immunization series in individuals having received one dose of ChAdOx1 (AstraZeneca) with an mRNA vaccine. However, data on safety and reactogenicity of this heterologous regimen are still scarce. The aim of this study was therefore to compare the reactogenicity and the frequency of medical consultations after boost vaccination in a heterologous regimen with ChAdOx1 and mRNA-vaccines (BNT162b2, BioNTech/Pfizer or mRNA-1273, Moderna) to homologous regimens with ChAdOx1 or mRNA-vaccines, respectively. METHODS: In an observational cohort study reactogenicity and safety were assessed 14-19 days (short-term) and 40 to 56 days (long-term) after the boost vaccination using web-based surveys. In the short-term survey solicited and unsolicited reactions were assessed, while the long-term survey focussed on health problems leading to medical consultation after the vaccination, including those that were not suspected to be vaccine-related. RESULTS: In total, 9146 participants completed at least one of the surveys (ChAdOx1/ChAdOx1: n = 552, ChAdOx1/mRNA: n = 2382, mRNA/mRNA: n = 6212). In the short-term survey, 86% with ChAdOx1/mRNA regimen reported at least one reaction, in the ChAdOx1/ChAdOx1 and mRNA/mRNA cohorts 58% and 76%, respectively (age and sex adjusted p < 0.0001). In the long-term survey, comparable proportions of individuals reported medical consultation (ChAdOx1/ChAdOx1 vs. ChAdOx1/mRNA vs. mRNA/mRNA: 15% vs. 18% vs. 16%, age and sex adjusted p = 0.398). Female gender was associated with a higher reactogenicity and more medical consultations. Younger age was associated with a higher reactogenicity, whereas elderly people reported more medical consultations. CONCLUSION: Although the short-term reactogenicity was higher with the heterologous regimen than with the homologous regimens, other factors such as higher efficacy and limited resources during the pandemic may prevail in recommending specific regimens.

[Prescribing behavior of Bavarian general practitioners at the inpatient-outpatient interface within the context of the Bavarian active substance agreement-qualitative results of the WirtMed Study]. / Verordnungsverhalten von bayerischen Hausärzt*innen an der stationär-ambulanten Schnittstelle vor dem Hintergrund der Bayerischen Wirkstoffvereinbarung ­ Qualitative Ergebnisse der WirtMed-Studie.

BACKGROUND AND OBJECTIVES: In 2014, the Association of Statutory Health Insurance Physicians of Bavaria introduced the active substance agreement (WSV) for the transparent control of pharmaceutical expenditure within the framework of the efficiency principle (§ 12 of the Fifth Book of the German Social Code [SGB V]). It replaced the prescribing target scheme. Regarding the role of the WSV, the article presents the reasons of the general practitioners (GPs) for or against a further prescription of drugs from the hospital. MATERIALS AND METHODS: In a qualitative study design, individual interviews (n = 18) and two focus groups (n = 10) were conducted with Bavarian GPs between November 2019 and March 2020 and evaluated according to qualitative content analysis. RESULTS: With the introduction of the WSV, recourse concerns decreased for GPs overall. Patient-oriented care and the professional correctness of therapy decisions are of great importance in prescribing, ahead of cost-effectiveness. Economic challenges arise with discharge medication, especially with the lead substance target of oral anticoagulants, the generic targets for antidiabetics, and for therapeutics for the cardiovascular system. Generally criticized are drug discount contracts, which often lead to drug changes after hospital discharge. There are individual reports of a "predominance" of hospital physicians when prescribing, which is contrary to their own economic actions as GPs. According to the GPs, there is a lack of cross-sectoral cost responsibility. CONCLUSIONS: In the view of GPs, a smooth interface transition is not yet available in the outpatient sector despite a framework agreement on discharge management and the new control system of the WSV. An economical supply of drugs continues to require political discussion across sectors, but also across federal states.

Controlling Prescribing through "Preferred Drug" Targets-The Bavarian Experience.

BACKGROUND: The rising costs of drugs are putting health care systems under pressure. We report on the Bavarian Drug Agreement, which employs prescribing targets for preferred and generic drugs in ambulatory care. Under this agreement, providers are regularly profiled with individual feedback but also possible sanctions. We investigated the degree to which targets were being met (or not) and why failure occurred. METHODS: We analysed prescribing data aggregated by practice for the quarter 1/2018. We chose eight specialisation groups and analysed their drug targets with a high prescribing volume, widely missed drug targets (<90%), and drugs preventing drug target achievement. Characterisation of drug targets and preventing drugs was undertaken. RESULTS: Drug targets with a high prescribing volume are mostly achieved, while highly missed drug targets mostly do not affect the main indication area of the specialisation groups considered. Generic drug targets seem to be more easily achieved than recommended drug targets. Paediatrics accounts for the largest number of missed drug targets. CONCLUSIONS: The Bavarian tool implemented uses the prescribing volume (DDD) and price components to evaluate the prescription behaviour of physicians. Well-established drugs with demonstrated effectiveness, safety, and lower costs are preferred. Nevertheless, me-too drugs, combination drugs, costly innovations with unclear value, and drugs with application methods of variable convenience challenge the drug prescribers and are reasons for missed drug targets.

Treatment thresholds and minimal clinically important effect sizes of antiosteoporotic medication-Survey among physicians and lay persons in Germany.

BACKGROUND: Patient decisions to take preventative treatments for osteoporosis depend on their perceptions of fracture risk, medication effect sizes (ES) of benefits and harms. However, physicians and lay persons may have differing perceptions of risks and medication efficacy. Both tend to overestimate medication benefits. This study surveyed at what risk physicians would prescribe and lay persons would be willing to take bisphosphonates, the minimum ES both groups do demand and the physicians estimates of the actual benefit of bisphosphonates. DESIGN: Cross-sectional online questionnaire survey. METHODS: Respondents were confronted with a case vignette with an osteoporotic patient (10-year femoral fracture risk: 32%). They were asked at what threshold of 10-year-risk of femoral neck fracture they would prescribe or take a drug. They were asked for the minimum ES (absolute risk reduction, ARR) they demand from bisphosphonates to prescribe or take them. Physicians were asked to provide their estimate of the actual ARR of bisphosphonates. RESULTS: 114 physicians and 140 lay persons answered (convenience sample/snowball distribution). The 10-year-risk threshold of lay persons (Mdnlay = 60%) willing to take medication was twice as high as the physicians' threshold (Mdnphy = 30%) to prescribe it (p < .001). The median minimum ARR physicians demanded for bisphosphonates prescription was 17%, whereas lay persons demanded 22% (p < .001). Physicians estimated the actual ARR of bisphosphonates to be 12%. This estimated effect size was below their own minimum threshold for prescription. CONCLUSIONS: Lay persons tolerate a higher fracture risk and demand a larger benefit of antiosteoporotic medication for fracture prevention than physicians. Physicians demand higher minimum benefits than their own estimates which in turn are above the benefit evidence suggests. Physicians should be more familiar with ES of antiosteoporotic drugs concerning patient outcomes and actively advise lay persons before preventive treatment decisions are taken.

One year of general practice during the COVID-19 pandemic - presentation and evaluation of digital medical education.

Background and teaching situation: The SARS-CoV-2 pandemic had a substantial didactic impact on medical teaching. In Erlangen, the lecture "General Practice" was offered asynchronously and digitally in an inverted-classroom concept. Contents were available via a learning platform. The lecture was presented using annotated videos, consolidation materials and control questions. A forum encouraged for discussions and feedback and collected in-depth aspects for a case-based video consultation. The aim of this work is to evaluate and critically examine the digital teaching concept during the SARS-CoV-2 pandemic. Methodology: Two semester cohorts evaluated the lecture. Overall impression of the lecture, didactic elements, suitability and the desired future lecture format were surveyed quantitatively. Free text answers were evaluated by means of qualitative content synthesis. Results: In terms of overall impression, the students (N=199) rated the lecture on average as "very good" (M=1.41, SD=.57). Digital methods were perceived as suitable for supporting self-study, and digital usage was rated as unproblematically (M=1.18, SD=.50). Desired future teaching formats were blended learning concepts (79.4%). Organisation, structure and content presentation were highly appreciated. The time for completing the course was perceived critically. The students urged for more practical and consolidating lecture work. Discussion and implications: The results illustrate high acceptance of digital teaching and underline the demand for future blended learning concepts. It is particularly important to better consider the students' time investment and practical relevance of digital self-learning mechanisms.

Active monitoring of adverse reactions following COVID-19 and other vaccinations: a feasibility study as part of the CoVaKo project.

BACKGROUND: The Corona-Vakzin-Konsortium project (CoVaKo) analyses the efficacy and safety of COVID-19 vaccines in a real-world setting, as well as breakthrough infections in Bavaria, Germany. A subproject of CoVaKo aims to identify adverse reactions of the COVID-19 vaccine and compare these to adverse reactions of other vaccines in an online survey. In a preceding feasibility study, the study materials were tested for comprehensibility, visual design, and motivation to participate, as well as for their ability to be implemented and carried out in primary care practices and vaccination centres. METHODS: We used a mixed-methods research design. First, three focus groups consisting of general population participants were organised to evaluate the study materials and survey. Second, a test roll-out was conducted in vaccination centres and primary care practices that involved implementing and quantitatively evaluating the online survey. Third, interviews were conducted with participating general practitioners and heads of vaccination centres four weeks after the test roll-out. RESULTS: Parts of the information and registration form proved incomprehensible, specifically regarding the recruitment material and/or online survey. For example, headings were misleading given that, relative to other vaccinations, the COVID-19 vaccination was overemphasised in the title. Participants requested additional information regarding the procedure and completion time. Within 31 days, 2199 participants, who received either a COVID-19 vaccination (99%) or at least one of the control vaccinations (1%), registered for the study. Participants (strongly) agreed that the registration process was easy to understand, that the completion time was reasonable, and that the technical setup was straightforward. Physicians and heads of the vaccination centres perceived the study as easy to integrate into their workflow. The majority expressed willingness to participate in the main study. CONCLUSIONS: Our study indicated that identifying and documenting adverse reactions following vaccinations using an online survey is feasible. Testing materials and surveys provided valuable insight, enabling subsequent improvements. Participation from health professionals proved essential in ensuring the practicality of procedures. Lastly, adapting the study's organisation to external fluctuating structures and requirements confirmed necessary for a successful implementation, especially due to dynamic changes in the nation's COVID-19 vaccination strategies. TRIAL REGISTRATION: The trial was retrospectively registered at the "Deutsches Register Klinischer Studien" (DRKS-ID: DRKS00025881 ) on Oct 14, 2021.