Efficacy of COVID-19 vaccines: a systematic review and network meta-analysis of phase 3 randomized controlled trials.

Several vaccines have been approved for the prevention of COVID-19. However, no head-to-head trials comparing their clinical efficacy have been performed. This network meta-analysis aims to identify those, among the competing existing vaccines, conferring the maximum protection against COVID-19. A literature search was done in Medline (via PubMed), Embase and Cochrane Library databases for phase 3 randomized controlled trials evaluating the efficacy of different COVID-19 vaccines. Search results were screened and eligible studies were included to perform a network meta-analysis in software 'R' version 4.1.2 using a random effect model. Cochrane's 'Risk of Bias tool (RoB2)' was used for quality assessment. Raw data from the included studies was used for network meta-analysis. Assessment of inconsistency was not possible as no study compared two or more vaccines directly. A forest plot for indirect comparison of various COVID-19 vaccines was obtained. Rankogram and 'P' scores were obtained to rank the vaccines based on the indirect evidence of their comparative efficacy. A total of 17 randomized controlled trials evaluating the efficacy of 16 COVID-19 vaccines, were included in the network meta-analysis. A total of 361,386 participants was included in this network meta-analysis. Overall risk of bias among included studies was of 'some concern'. All the COVID-19 vaccines had a statistically significant reduction of risk for contracting symptomatic SARS-CoV-2 in comparison to the placebo, however, the maximum protection (RR 0.05) was with BNT126b2. The indirect comparison also revealed BNT126b2 vaccine confers the highest protection against symptomatic SARS-CoV-2 infection in comparison to all others included, with a 'P' score of 0.9771 followed by mRNA-1273, rAD26 & rAD5 and NVX-CoV2373. The evidence generated from this network meta-analysis indicates the good efficacy of all the included vaccines in preventing symptomatic COVID-19 as compared to placebo. The BNT126b2 vaccine was found to provide the highest protection against symptomatic SARS-CoV-2 among all included followed by mRNA-1273, rAD26 & rAD5, NVX-CoV2373 and others.

Efficacy and safety of potential vaccine candidates against coronavirus disease 2019: A systematic review.

Search for an effective and safe vaccine to prevent transmission of current pandemic is an unmet need. This study reviews and compares the available early phase clinical data of vaccine candidates which have reached phase 3 of clinical development. The latest update of "DRAFT landscape of coronavirus (CoV) disease 2019 candidate vaccines (October 2, 2020)" released by the World Health Organization was accessed to identify the potential vaccine candidates. The full text articles (published and/or preprint) of data of early clinical trials of the selected vaccines were accessed from the links provided in the same document, PubMed and/or medRxiv.com. After extraction and synthesis, the data were critically evaluated for the study efficacy and safety outcomes. Of the total 193 candidate vaccines 10 were found to reach phase 3 of the clinical development. Nine of these were included in the evaluation process. In all of the included studies, immunogenicity and serious adverse events/local or systemic adverse events/laboratory parameters abnormality was considered as efficacy and safety outcomes respectively. Immunogenicity response with most of the vaccines was either higher than or similar to the respective controls except one (recombinant adenovirus type 26 COV2 [Ad26.COV2.S]) for which it was less than that in control. Overall adverse events (related and/or unrelated) were more with vaccines than those with respective control(s) in three studies, in other two, these were similar whereas in one study, the events were less in the vaccine group than in control group and in the rest, data described were descriptive only without any mention for the same for the control. In conclusion all studies showed immunogenic response to target protein of severe acute respiratory syndrome CoV-2 and which was higher than the respective control except for Ad26.CoV2.S. Many of the vaccines caused more adverse events than the controls, however most were mild and transient and/or manageable.

Implementation of Objective Structured Practical Examination in Formative Assessment for Undergraduate Practical Pharmacology.

Context: At present, the method of practical assessment in pharmacology focuses on cognitive and subjective domains. Ideally, it should be objective and comprehensive. Objective: To compare marks obtained in two types of exams, objective structured practical examination (OSPE) and traditional practical examination (TDPE), in order to assess faculty members' and students' perception of OSPE Methodology: Sixty students having 75% attendance were included in the present study. Both OSPE and TDPE were conducted and marks obtained in each of the two exams were compared. Perceptions of students and faculty members were assessed on the basis of Likert- scale. Result and discussion: The percentage of mean marks obtained in TDPE (67.5±2.24) was higher than in OSPE (66.5±2.78), but the results were not statistically significant (p=0.6). This may be due to first time exposure of OSPE and belief that marks would not be counted in internal assessment. Ninety five percent of students agreed that practical skills and knowledge acquired during OSPE would be also helpful after graduation, and 83.33% of participants admitted that personality, gender and other student-related factors did not affect scoring in OSPE. Eighty five percent of students and all faculties were willing to implement OSPE as an assessment tool. All faculties were in favour of OSPE due to its very low variability and because it motivated students learn skills as well subject more. Conclusion:Objective structured practical examination is comparable to TDPE as assessment tool for pharmacology practical examination in terms of marks obtained by students, while satisfaction reported by faculties and students regarding various aspects of OSPE is much more in favour of the latter.

Students' Perception on Online Teaching and Learning during COVID-19 Pandemic in Medical Education.

Introduction: The COVID-19 pandemic has changed the method of learning in medical education and forced us to switch over to the online mode of learning. The aim of the present study was to assess students' opinion on online learning in the time of COVID-19. Method:This is a descriptive cross-sectional questionnaire-based study conducted among undergraduate medical students. The closed, open-ended and validated questionnaires were administered to students to get feedback on utility, feasibility, suitability, effectiveness online learning as well as problems faced during e-learning and suggested solutions to them. Results:About 62.7% of undergraduates had internet access. Sixty seven percent of undergraduates were willing to actively communicate with their classmates and instructors electronically, whereas 64.9% of students were communicating online comfortably. Also, 82.20% of students were able to clear their doubt from teacher whenever required. Only 38 (20.5%) of students had equated online learning from home to conventional lectures in a lecture hall. However, 28.6% of students felt comfortable to learn from home in the pandemic era. Students (66.5%) wanted proper breaks, which would enable them to get sufficient time to think about the topic and frame their questions to clear their doubts. About 80% of students wanted that a sufficient number of questions should be asked to transform online learning sessions into interactive approaches. They highlighted distractions during online learning at home, problems of network accessibility, connectivity, lack of synchrony between audio and video, and audio disturbance. Conclusions:More than half of our students prefer classroom learning because it facilitates better teacher-student interactions, stimulates understanding, provides a distraction-free environment, and permits an appropriate pace of learning, encouraging interactivity and independence from technology.

Efficacy of Interferon-ß in Moderate-to-Severe Hospitalised Cases of COVID-19: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: Interferon-ß, as with several other anti-viral agents, has been investigated as a treatment option for COVID-19 as a repurposed drug. The present study is a systematic review and meta-analysis of interferon-ß to determine its efficacy among moderate-to-severe COVID-19 patients. METHODS: A systematic literature search was done using relevant terms for 'COVID-19' and 'interferon-ß'. Randomised controlled trials (RCT) evaluating the efficacy of interferon-ß in COVID-19 were included. Data were extracted for outcome measures, namely mortality, time to clinical improvement and length of hospital stay. Random effects meta-analysis was performed using RevMan V.5.4.1 to calculate overall effect estimate as odds ratio/hazard ratio for categorical variables and mean difference for continuous variable. RESULT: Eight RCTs were eligible for qualitative synthesis and seven for meta-analysis. The overall effect estimate (odds ratio [OR] 0.59; 95 % CI 0.91, 1.12) and (mean difference [MD] - 1.41; 95 % CI - 2.84, 0.02) indicated no statistically significant difference between effect of IFN-ß and that of control on mortality and length of hospital stay, respectively. However, the overall effect estimate (hazard ratio [HR] 1.95; 95 % CI 1.36, 2.79) denoted a favourable effect of INF-ß on reducing the time to clinical improvement in moderate-to-severe COVID-19 patients. CONCLUSION: Addition of interferon-ß to standard of care resulted in significant reduction in time to clinical improvement but no significant benefit in terms of reduction in mortality and length of hospital stay in moderate-to-severe cases of COVID-19.

Efficacy and safety of lopinavir-ritonavir in COVID-19: A systematic review of randomized controlled trials.

BACKGROUND: Lopinavir-ritonavir is a repurposed drug for coronavirus disease-2019 (COVID-19). In this study, a pooled effect of lopinavir-ritonavir on mortality, virological cure, radiological improvement and safety profile in COVID-19 patients has been evaluated. METHODS: The databases were searched for comparative randomized controlled studies evaluating the efficacy and/or safety of lopinavir-ritonavir in COVID-19 patients. The mortality outcome was pooled as a risk difference (RD) with 95% CI. The virological cure, radiological improvement and adverse events were pooled as risk ratio (RR) with 95% CI. All outcomes were pooled using the Mantle-Hanzle method random effect model. The heterogeneity was assessed using the I2 test. RESULTS: Out of 82 full text assessed, seven studies were included in the analysis. The included studies had five different control interventions: supportive care (n=4), umifenovir (arbidol) (n=2), navaferon (recombinant anti-tumour and anti-virus protein) (n=1), lopinavir-ritonavir+novaferon (n=1) and lopinavir-ritonavir+interferon beta 1b+ribavirin (n=1). Lopinavir-ritonavir group did not show significant difference in mortality [RD: 0.00 (95% CI: -0.01, 0.02), I2=0], virological cure [RR: 1.06 (95% CI: 0.85, 1.31), I2=0%], radiological improvement [RR: 0.81 (95% CI: 0.62, 1.05)] and adverse events [RR: 2.59 (95% CI: 0.17, 38.90), I2=75%] than supportive care. Similarly, no difference was observed for any efficacy outcomes between lopinavir-ritonavir and other control interventions. We observed significantly high risk of adverse events with lopinavir-ritonavir as compared to umifenovir [RR: 2.96 (95% CI: 1.42-6.18); I2=0%]. CONCLUSION: There is no benefit of the addition of lopinavir-ritonavir to the standard care in COVID-19 patients.

Evaluation of Medicine Exposure During Pregnancy at a Tertiary Center of an Indian State.

Context:Prescribing drugs in pregnancy is a challenging approach for doctors. Objective:To evaluate drugs used in pregnancy. Method:A prospective, cross-sectional, descriptive study was carried out by collecting and evaluating prescriptions on various parameters. Results:More than 50% of antenatal care attendees belonged to the 18-24 age group, and 102 (41.46%) were primigravidae. The main presenting complaints were abdominal pain (25.16%), followed by nausea and vomiting (22.60%) and fever (11.14%); the maximum number of visits to hospital was seen in the first trimester (40.53%), followed by the third trimester (38.42%). It was observed that 25.78% of prescriptions did not contain any medicine. The average number of prescribed medicines was 2.32, with the lowest in the first trimester (1.77) and the highest in the second trimester (2.78). It was noticed that 74.11% and 71.26% of all prescribed medicines were from essential medicine list and generics, respectively. Of all prescribed drugs, 11.52% were antimicrobials, and 4.11% injectable dosage forms. Vitamins and minerals were the preferred prescribed medicines (34.82%), followed by antimicrobial agents (11.52%) and doxylamine plus pyridoxine (10.16%). Also, doctors who made the drug choice during antenatal visits were more confident in evidence-based safety as per New Pregnancy and Lactation Rule (PPLR); 45.37% of drugs were prescribed from category A, followed by 38.25% from category B and none from group X. Conclusion:Doctors were concerned about prescribing safer drugs in pregnancy and were more confident in evidence-based medication.

Adverse drug reactions reporting by undergraduate medical students in a tertiary care teaching hospital of India: Content and quality analysis in comparison to physician reporting.

BACKGROUND: An important challenge to spontaneous reporting system is underreporting. The sensitization and involvement of undergraduate medical students can reduce underreporting in pharmacovigilance program. OBJECTIVE: To analyze the clinical characteristics and reporting quality of adverse drug reactions (ADRs) by undergraduate medical students in comparison with physicians' reporting. METHODS: We sensitized the second professional year undergraduate medical students about pharmacovigilance and asked them to submit reports of ADR observed during their clinical posting from January to December 2015. We compared students' reports with those sent by physicians (Department of Medicine and Allied Branches, Paediatric, Obstetrics and Gynaecology) of our institute during the same time period. We included ADRs of "certain," "probable," or "possible" categories as per the World Health Organization causality definitions in analysis of both groups. We excluded "unlikely," "unclassified," and "unclassifiable" causality ADRs from the analysis due to questionable association of reactions with suspected drugs. We collected data of demographics, pattern of ADRs, causative drugs, seriousness, other clinical characteristics, and quality of reporting. RESULTS: We analyzed a total number of 176 students' reports having 269 ADRs and 143 physicians' reports covering 180 ADRs. The students predominantly reported ADRs of single drug suspect (84.09% vs. 43.35%), "probable" causality (63.94% vs. 21.11), and augmented type reactions (67.29% vs. 55%) than physicians. Both groups did not differ in reporting of serious reactions (6.25% vs. 9.09%). Students most frequently suspected gastrointestinal disorders (35.68%), whereas physicians most frequently reported skin and appendages disorders (41.11%). Students and physicians more commonly suspected ADRs due to systemic anti-infective (33.64%) and nervous system (42.07%) class of drugs, respectively. The quality analysis suggested no substantial difference in most domains of ADR reporting among both groups. CONCLUSION: Students' reported valuable and clinically relevant ADRs. Medical students should be exposed to ADR reporting during their clinical teaching posting and should be actively involved in pharmacovigilance program to improve detection rate.