A Study to Assess the Quality of Reporting of Animal Research Studies Published in PubMed Indexed Journals: A Retrospective, Cross-Sectional Content Analysis.

OBJECTIVES: A complete and concise pre-clinical experimental research gives detailed information about the disease-specific model, prevents duplication, and saves animal life, money, as well as time. It will also allow readers to effectively interpret and evaluate the work and ensure that others can replicate the experiments described. The present study was conducted to assess the adequacy of animal details provided in published experimental animal studies. METHODS:  All in vivo studies published as full-text articles in two PubMed indexed journals (one Indian and one international) from January 2011 to December 2019 and satisfying the inclusion norms were included. A checklist consisting of 27 discrete items subdivided under three domains, viz. animal details, disease model, and guidelines, was used. Every article was assessed by two investigators independently for determining the reporting quality. RESULTS:  One hundred and seventy-seven studies satisfied the inclusion criteria. Age or age range was reported in 20.34% of the articles in the Indian journal and 5.88% articles in the international journal (p=0.019). Housing and husbandry details were reported in all the articles published in the international journal and 82.7% of the articles in the Indian journal (p=0.001). The disease/pathology studied was given in 70.62% of articles published in the Indian journal and 86.27% of articles published in the international journal (p=0.029). None of the studies provided details of genetic modification, health status, sample size calculation, steps taken to minimize bias, and implementation of randomization. CONCLUSION: There is a need for optimal reporting of certain relevant animal details, disease models, experimental procedures, sample size calculation, and adherence to guidelines by the researchers for which the reporting was found to be sub-par to improve reproducibility and validity of animal research.

Drug use pattern for emergency psychiatric conditions in a tertiary care hospital: A prospective observational study.

PURPOSE: Psychiatric emergencies (PEs) are defined as acute disturbances of thought, mood, behavior, or social relationships requiring immediate interventions. The common emergency psychiatrics are attempted suicide, severe anxiety, schizophrenia, acute psychosis, substance abuse, acute panic attacks, drug toxicities, and extrapyramidal reactions. Emergency physicians in the general hospital may face the challenge of assessing and managing patients in PEs. This study was conducted to evaluate the clinical pattern and drug use pattern for PEs at a tertiary care hospital. MATERIALS AND METHODS: This was a cross-sectional, observational study where patients presenting to emergency medical services of a tertiary care hospital were recruited after approval from Institutional Ethics Committee and written informed consent. Demographic details, diagnosis, medication details, cost of the treatment, and adherence to guidelines in the management of emergency psychiatric conditions were assessed using a validated questionnaire. Descriptive statistics was applied to analyze the data. RESULTS: In 110 patients, a total number of drugs prescribed were 463 (mean: 4.21 drugs/prescription). The most commonly used psychotropic drug in emergency setting was found to be risperidone (19.39%), followed by lorazepam (13.60%) and clonazepam (4.28%). The most common diagnoses were substance abuse (32.72%) and schizophrenia (21.81%). About 74.5% of the physicians prescribed drugs abiding by the standard guidelines. The average total cost incurred by patients was about Rs. 366. CONCLUSION: The most commonly used drugs in emergency treatment found in this study are risperidone, followed by lorazepam and haloperidol.

Assessing completion reports for compliance with institutional ethics committee-approved protocols: An observational study.

BACKGROUND: Protocol non-compliance in clinical research studies is common and can affect both patient safety and data integrity. There are no published studies which actively looked for non-compliance. The present study was carried out, against this background, with the objective of assessing the proportion of protocol non-compliance and evaluating those aspects of protocol where there was non-compliance. METHODS: The study completion reports that were submitted to the institutional ethics committee for the period January 2017 to December 2017 were compared with the approved protocol. A checklist for recording protocol non-compliance was developed, which was validated by five experts and consisted of a 12-point checklist with responses such as yes, no, not applicable, and insufficient information. RESULTS: Out of 193 studies, prospective observational studies were n = 120 (62.17 %), retrospective studies were n = 39 (20.21%), interventional studies n = 28 (14.51 %), and observational studies with both prospective and retrospective study design were n = 6 (3.11%). The study objective was modified in n=18 (9.32%) studies. Only n = 14 (7.24%) satisfied the selection criteria. Six studies (3.10%) did not collect the data as mentioned in the protocol. Fifty-eight studies (30.05%) did not achieve the calculated sample size, whereas n = 78 (40.41%) did not complete the study as per the stipulated study duration. Contrary to 180 protocol deviations found in this study, only 14 protocol deviations were reported by the principal investigator. Aspects like blinding and randomisation, which are relevant to interventional studies (n = 28), showed 100 % compliance. CONCLUSION: The research protocol is not adhered to in all aspects. Adequate training to investigators will help prevent non-compliance and enable us to conduct studies with higher ethical and scientific integrity.

Reports of site monitoring visits by institutional ethics committees in an Indian tertiary care hospital: A retrospective analysis.

The monitoring of clinical trials is an integral function of the institutional ethics committee (IEC)to ensure the ethical conduct of research. The National Ethical Guidelines for Biomedical and Health Research Involving Human Participants, 2017, of the Indian Council of Medical Research, underline a strong need for active monitoring of clinical trials. A previous study by the authors, of research studies initiated between 2008 and 2010, had found many lapses after site monitoring. In the present study, 12 clinical studies-both sponsored and investigator initiated-were monitored by members of the King Edward Memorial Hospital (Mumbai) IEC between 2011 and 2017. The most common violations seen were related to informed consent (8/12 sites). The other violation themes were lack of investigator understanding of protocol (6/12), deviation from the investigational plan (5/12), non-reporting of the study's progress to the IEC (4/12), and patient recruitment prior to IEC approval (2/12). The IEC took various corrective actions, such as ordering retaking of consent and good clinical practice (GCP) re-training and requiring interim reports, explanations for deviations, upgradation of facilities, and payment of pending compensation. The IEC even froze review of protocols from a frequently defaulting Principal Investigator's (PI) site and put study recruitment on hold for the same PI. This study demonstrates that active site monitoring by IECs is a must for ensuring the ethical conduct of studies.

Perception of postgraduate students in pharmacology toward animal simulation model.

OBJECTIVE: The objective of the study is to evaluate the perception of postgraduate pharmacology students toward computer-simulated method (CSM) in comparison to the prevalent isolated live tissue-based bioassay method. MATERIALS AND METHODS: A questionnaire-based survey was conducted in 30 postgraduate pharmacology students who had used the animal simulation software and had completed at least five isolated tissue experiments. Students' opinions on the usage, logistics, advantages, disadvantages, and usefulness of CSM compared to live animal experiments (LAE) were analyzed. RESULTS: Four tissues were used for LAE, whereas with CSM, students could perform experiments using 11 different tissues. Of the total nine bioassay methods, students had performed six assay methods using both LAE and CSM. Majority of the students (23/30) agreed that CSM reduces anxiety, technical errors and is less time consuming when used before LAE. Most of the students agreed that CSM can be used for difficult, lengthy experiments (19/30), and for UG/PG teaching (19/30). However, opinions regarding replacing LAE with CSM in PG teaching were divided (agree: 7, neutral: 12, and disagree: 12). CONCLUSION: CSM should be integrated alongside LAE to complement, reinforce, and enhance learning from other techniques.

Intra-articular injections of ketamine and 25% dextrose improve clinical and pathological outcomes in the monosodium iodoacetate model of osteoarthritis.

BACKGROUND: The study evaluated the effect of intra-articular injections of ketamine and 25% dextrose with triamcinolone acetate (TA) and hyaluronic acid (HA) on joint pathology and pain behavior in monosodium iodoacetate (MIA)-induced osteoarthritis (OA) in experimental mice. METHODS: In phase I, the MIA-induced OA model was standardized. In phase II, mice were divided into three groups: disease controls (DC), ketamine 12 mg/kg (K12) and ketamine 24 mg/kg (K24) to select an effective dose of ketamine for phase III. In phase III, the groups were: DC, normal controls (NC), K24, 25% dextrose (D25) - 10 µL, TA 6 mg/kg, and HA - 3.5 mg/kg. The effect of ketamine was compared with the standard drugs - TA and HA. In phases II and III, after 7 days following the induction of OA, animals were subjected to weekly behavioral tests and biweekly drug administration from week 2 to week 4. Subsequently, after 4 weeks knee joint samples were collected and sent for histopathological evaluation to a veterinary pathologist. RESULTS: In phase I, the DC group showed significant OA changes as compared to NC on knee joint histopathology scoring. In phase II, all the behavioral tests and knee joint histopathology results demonstrated a significant improvement with K24 as compared to DC. In phase III, significant differences were found between DC vs. HA, DC vs. D25, DC vs. K24, K24 vs. TA, HA vs. TA for open field test and hot plate test (p<0.001), whereas HA and ketamine showed comparable results for these tests. There was a significant improvement in D25, TA and K24, HA groups as compared to DC in histopathology scores, (p<0.05). CONCLUSIONS: The NMDA antagonist effect of ketamine and the proliferative effect of 25% dextrose showed a reduction in pain and disease activity in the OA model.

Impact of recent regulatory notifications on an institutional ethics committee.

The Government of India came out with a slew of notifications to streamline clinical research in the beginning of 2013 in response to the Supreme Court's orders and a Parliamentary Standing Committee's report. The notifications greatly influenced the structure, review process, outcomes and administration of ethics committees across India. In this study, we attempted to objectively evaluate the impact of these notifications on our institutional ethics committee's (IEC) structure, review process, outcomes and administration. The results revealed that though the number of regulatory studies reviewed by our IEC remained the same, the number of studies actually approved decreased with an increase in the turnover time. The number of serious adverse events (SAEs) reported also fell, although the number of meetings held to discuss these SAEs increased significantly. The administrative workload rose with increased documentation. Though the annual income of the IEC fell marginally, the expenses shot up. We believe that the notifications definitely had an impact on the structure, review process, outcomes and administration of our IEC, although it remains to be seen whether they had a real impact on the research participants' safety and well-being.

Evaluation of antiepileptic effect of S-adenosyl methionine and its role in memory impairment in pentylenetetrazole-induced kindling model in rats.

BACKGROUND: Epilepsy is the third most common cause of neurological disability worldwide. Despite the introduction of antiepileptic drugs (AEDs) in the past 20years, the seizures of around 30% of patients with epilepsy remain refractory to available treatment. Also, available AEDs and the disease itself have the potential to exert detrimental effects on cognitive function and therefore compromise patient wellbeing. S-adenosyl methionine has potential antiepileptic and memory-enhancing properties because of its involvement in the transmethylation reaction. OBJECTIVES: The present study was designed to evaluate the antiepileptic effect of S-adenosyl methionine and its role in memory impairment in the pentylenetetrazole (PTZ)-induced kindling model in rats. MATERIALS AND METHODS: The antiepileptic effect of 2 doses of SAM (50 and 100mg/kg) was tested by evaluating seizure severity score and seizure latency in the pentylenetetrazole-induced kindling model in rats. At the end of the study, spatial memory was evaluated in an elevated plus maze (EPM) test, and animals were sacrificed for estimation of oxidative stress markers in brain tissue homogenate. RESULTS: A higher dose of SAM (100mg/kg) exhibited an increase in seizure latency and a decrease in seizure severity score, suggesting its antiepileptic activity in the PTZ-induced kindling model. Also, the administration of SAM (50 and 100mg/kg) showed a decrease in transfer latency in the EPM test compared to the disease control group (p<0.0001). Biochemical analysis of rat brain tissue revealed significantly decreased malondialdehyde (p<0.0001) and increased glutathione (GSH) (p<0.0001) in the SAM 100-mg/kg group compared with that in the disease control group. CONCLUSION: The results demonstrated that S-adenosyl methionine exerts antiepileptic, memory-enhancing, and antioxidant properties in a pentylenetetrazole-induced kindling model of epilepsy.

An Audit of Protocol Deviations Submitted to an Institutional Ethics Committee of a Tertiary Care Hospital.

Protocol deviations (PDs) may jeopardize safety, rights, and welfare of subjects and data integrity. There is scarce literature and no guidelines for Institutional Ethics Committees (IECs) to process PD reports. The PD reports submitted to IECs from Jan 2011 to August 2014 were analyzed retrospectively. Types of studies reporting PDs, category and type of PDs, PD rate per participant, time of reporting PD since its occurrence and corrective actions stated by principal investigator (PI) for major deviations were noted. Out of 447 PDs from 73/1387 total studies received during study period, 402 were from 126 pharma studies. Investigator initiated studies and dissertations reported negligible PDs. Median number of PDs was 4 per protocol. Out of 447 PDs, 304 were related to study procedure, 87, 47 and 9 were from safety, informed consent document (ICD) and eligibility category respectively. The most common reason for PDs was incomplete ICD (22/47). Maximum study procedure related PDs were due to patient visiting outside window period (126/304). Thirty five of 87 PDs were due to missed safety assessment. The overall PD reporting rate per participant was 0.08. In 90% of reports, date of occurrence of PD was not specified. The median delay for reporting PDs after occurrence was 94 days. PDs classified as Major were 73% (323/447). The most common corrective actions stated by PI were participant counseling (85/323) and caution in future (70/323). The study findings emphasize the need for GCP training at regular interval of study team members. IEC have to be vigilant and visit sites frequently, take initiative and formulate guidelines regarding PD reporting.

Development of active learning modules in pharmacology for small group teaching.

BACKGROUND: Current teaching in pharmacology in undergraduate medical curriculum in India is primarily drug centered and stresses imparting factual knowledge rather than on pharmacotherapeutic skills. These skills would be better developed through active learning by the students. Hence modules that will encourage active learning were developed and compared with traditional methods within the Seth GS Medical College, Mumbai. METHODS: After Institutional Review Board approval, 90 second year undergraduate medical students who consented were randomized into six sub-groups, each with 15 students. Pre-test was administered. The three sub-groups were taught a topic using active learning modules (active learning groups), which included problems on case scenarios, critical appraisal of prescriptions and drug identification. The remaining three sub-groups were taught the same topic in a conventional tutorial mode (tutorial learning groups). There was crossover for the second topic. Performance was assessed using post-test. Questionnaires with Likert-scaled items were used to assess feedback on teaching technique, student interaction and group dynamics. RESULTS: The active and tutorial learning groups differed significantly in their post-test scores (11.3 ± 1.9 and 15.9 ± 2.7, respectively, P < 0.05). In students' feedback, 69/90 students had perceived the active learning session as interactive (vs. 37/90 students in tutorial group) and enhanced their understanding vs. 56/90 in tutorial group), aroused intellectual curiosity (47/90 students of active learning group vs. 30/90 in tutorial group) and provoked self-learning (41/90 active learning group vs. 14/90 in tutorial group). Sixty-four students in the active learning group felt that questioning each other helped in understanding the topic, which was the experience of 25/90 students in tutorial group. Nevertheless, students (55/90) preferred tutorial mode of learning to help them score better in their examinations. DISCUSSION: In this study, students preferred an active learning environment, though to pass examinations, they preferred the tutorial mode of teaching. Further efforts are required to explore the effects on learning of introducing similar modules for other topics.