Assessment of Knowledge and Awareness Among the Stakeholders of Clinical Research at the Site: A Collaborative, Electronic-Survey Approach to Identify the Indicators of Quality.

BACKGROUND: There has been a concern about the quality of clinical trials conducted in terms of data integrity, accuracy or ethical conduct. This study aimed to assess the tangible gap existing in knowledge and application of rules and guidelines among the Researcher, Research staff (RS) and Ethics Committee (EC) members - the three research stakeholders at the study sites. METHODS: A validated e-questionnaire with details for demography, role, years of experience, affiliation and questions on knowledge and understanding about their clinical research functions based on the New Drugs and Clinical Trials (NDCT) Rules 2019, including: 'Role and responsibility, Regulations, Reporting timelines, Documentation, Conflict of interest and Miscellaneous' was circulated among the seven research sites of one organization with their fourteen Institutional ECs, as part of planned annual survey. Responses with >60% correct answers were arbitrarily considered to represent adequate knowledge. RESULTS: Of 201 participants, there were 27.4% Researchers, 50.2% were from the EC and 22.4% RS. A greater proportion of the Researchers (43.6%) had >5 years of experience. The mean ± SD of correct answers obtained was 66.9 ± 14.77 and was statistically significant (p<0.05) among the groups, highest for the EC members (71.4 ± 11.51), those with 2-5 years of experience (68.4 ± 14.40), and least for the RS (56.8 ± 11.93). Researchers (> 90%) were aware of their role in the clinical trial agreement and the importance of the trial registration in the Clinical Trials Registry India. There were gaps in the knowledge on Informed Consent (IC) process and post-trial access. Awareness regarding the IC process was adequate among the RS (84%). Awareness that the responsibility of all delegation at the site finally lies with the Researchers was adequate (60%), but 20% incorrectly believed that the sponsor can have access to subject identification details. Deficiencies were noted regarding documentation, NDCT rules -2019 and serious adverse event (SAE) reporting process. Five percent answered that Data Clarification Forms were generated after reviewing the case report forms. The awareness that NDCT rules-2019 was not for medical devices, student projects or Investigator Initiated Studies was inadequate (56%). The EC members' awareness of roles and responsibilities was adequate (≥ 90%). Knowledge gaps were noted in EC monitoring of the ongoing trials (32%) and SAE reporting on the SUGAM portal (8.8%), where stakeholders can access the regulator's web services using a single window interface for clinical trial related activities. CONCLUSION: There are gaps in the knowledge of the 3 stakeholders at the site. Identifying and rectifying the gray areas will improve the site's performance. There is a need for regular training and assessments.

Rare clinical presentation of diffuse large B-cell lymphoma as otitis media and facial palsy.

Extra nodal presentation of Non Hodgkins Lymphoma (NHL) is a rare entity, and data available about the NHL that primarily involves of middle ear and mastoid is limited. We report a case of diffuse large B cell lymphoma (DLBCL), in a 2 year 8 month old boy, who developed otalgia and facial palsy. Computed tomography revealed a mass in the left mastoid. Mastoid exploration and histopathological examination revealed DLBCL. This case highlights the importance of considering malignant lymphoma as one of the differential diagnosis in persistent otitis media and/facial palsy.

Amtolmetin: A Reappraisal of NSAID with Gastroprotection.

Aim. To assess the gastrosparing effect of amtolmetin guacyl (AMG) against other nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with osteo-/rheumatoid arthritis. Methods. A literature search was done in the electronic databases (PubMed, Google Scholar, Embase, and Scopus) with key words "amtolmetin guacyl", "amtolmetin", and "arthritis"; filters were applied to obtain publications between 01-Jan-1985 and 01-Oct-2015, which were "clinical trials" in osteo-/rheumatoid arthritis patients and in "English language." Studies were assessed using the Jadad criteria and trials with score ≥ 3 were included in the analysis to compare the safety and efficacy of AMG against other NSAIDs. Results. Search yielded 19 publications of which 3 were included for analysis. Baseline characteristics of patients were comparable between the AMG group and other NSAIDs (diclofenac, celecoxib, and piroxicam) groups in all trials. Efficacy of AMG was similar to the other NSAIDs compared in the trials. The number of adverse events (AEs) reported was similar between both the groups; however, severe AEs reported were significantly lower in the AMG group. Of note was the significant lower number of duodenal ulcers after treatment in the AMG group. Conclusions. AMG has efficacy similar to other NSAIDs and a safer gastrointestinal AE profile when compared to the other NSAIDs.

Tight glycemic control and cardiovascular effects in type 2 diabetic patients.

Diabetes Mellitus (DM) with poor glycemic control is one of the leading causes for cardiovascular mortality in diabetic patients. Tight glycemic control with glycosylated haemoglobin of <7 gms% is recommended as a routine and < 6.5 gms% is recommended for young and newly diagnosed diabetics. Treatment goal aims at achieving near normal blood glucose level, and directed at management of other co morbid conditions such as obesity, hypertension and dyslipidemia. Oral hypoglycemic agents are the preferred drugs, alone or in combination. Preference for glitazones is declining due to the increasing evidences of associated adverse events. Gliptins appear as promising agents with lesser tendency to cause hypoglycemia, but their long term safety and efficacy is yet to be established. We emphasize the role of preventive measures in prediabetics and in established DM, treatment should be individualized and customized to minimize hypoglycemic effects and to retain quality of life.

Evaluation of Efficacy, Safety, and Tolerability of Fixed Dose Combination (FDC) of Halometasone 0.05% and Fusidic Acid 2% W/W Topical Cream Versus FDC of Betamethasone Valerate 0.12% and Neomycin Sulphate 0.5% W/W Topical Cream in the Treatment of Infected Eczematous Dermatosis in Indian Subjects: A Randomized Open-Label Comparative Phase III Multi-Centric Trial.

AIM: To evaluate the efficacy and safety of fixed drug combination (FDC) halometasone 0.05% and fusidic acid 2% (group A) vs FDC betamethasone 0.12% and neomycin sulfate 0.5% cream (group B) in acute or chronic infected eczematous dermatosis, through a randomized open-label, comparative, multicentric study. MATERIALS AND METHODS: A total of 152 patients were randomized to either Group A or Group B. EASI (Eczema Area and Severity Index), IGA (Investigator's global assessment), scale for severity of eczema, pruritus, and safety parameters were assessed at baseline, Day 5/Day 10, Day 10/20, and Day 20/Day 30 for acute/chronic cases. Skin swabs were tested at screening, Day 10, and end of the study. RESULTS: Staphylococcus aureus was the frequently encountered causative agent. There was a significant reduction within the study groups in EASI, IGA scales for severity of eczema, pruritus at various visits, compared to baseline. At the end of study, 83.87% in group A and 65.71% in group B were culture negative. Cure rate was 54.28% and 50% in group A and B, respectively. Five adverse events were reported in five patients, of which three patients withdrew from the study. CONCLUSION: Halometasone 0.05% and Fusidic acid 2% cream is effective, safe, well tolerated with comparable efficacy to the comparator in the treatment of acute and chronic infected eczematous dermatosis.

Efficacy and tolerability of fixed dose combination of metoprolol and amlodipine in Indian patients with essential hypertension.

BACKGROUND: This open-labeled, post-marketing study was conducted to assess the efficacy and tolerability of fixed dose combination of amlodipine and metoprolol extended release capsules in mild to moderate hypertension in adult Indian patients. MATERIALS AND METHODS: Of 101 enrolled patients, 64 drug naïve patients were treated with regimen A (amlodipine 5 mg + metoprolol 25 mg) and those with prior history of hypertension (n = 37) were treated with regimen B (amlodipine 5 mg + metoprolol 50 mg) for 8 weeks. Treatment response was assessed at week 4 and 8. Dose up titration to regimen B was carried out for those who failed to achieve the target blood pressure (BP) at week 4 in regimen A and additional antihypertensives were added to those in regimen B. Safety laboratory tests were performed at baseline and end of study. RESULTS: Mean age (±SD) of patients was 53.36 (±11.26) years and body weight (±SD) 63.40 (10.03) kg. Ninety five patients (94.06%) were only hypertensive and 6 (5.94%) had hypertension with history of coronary artery disease; mean duration (±SD) of hypertension was 42.50 (48.07) months. At baseline, patients had a mean (±SD) systolic blood pressure (SBP) and diastolic blood pressure (DBP) of 154.98 (±7.76) mmHg and 95.55 (±5.70) mmHg respectively. There was a statistically significant (P < 0.001) reduction of 12.16% and 14.69% in SBP, 11.49% and 14.65% in DBP at week 4 and week 8 respectively, compared to baseline. Normalization of overall BP was achieved in 49.49% and 70.71% patients at week 4 and 8, respectively. Peripheral edema was reported in 2.97% (3/101) patients. CONCLUSION: This combination was safe, efficacious, and well-tolerated in study population.

Data management in clinical research: An overview.

Clinical Data Management (CDM) is a critical phase in clinical research, which leads to generation of high-quality, reliable, and statistically sound data from clinical trials. This helps to produce a drastic reduction in time from drug development to marketing. Team members of CDM are actively involved in all stages of clinical trial right from inception to completion. They should have adequate process knowledge that helps maintain the quality standards of CDM processes. Various procedures in CDM including Case Report Form (CRF) designing, CRF annotation, database designing, data-entry, data validation, discrepancy management, medical coding, data extraction, and database locking are assessed for quality at regular intervals during a trial. In the present scenario, there is an increased demand to improve the CDM standards to meet the regulatory requirements and stay ahead of the competition by means of faster commercialization of product. With the implementation of regulatory compliant data management tools, CDM team can meet these demands. Additionally, it is becoming mandatory for companies to submit the data electronically. CDM professionals should meet appropriate expectations and set standards for data quality and also have a drive to adapt to the rapidly changing technology. This article highlights the processes involved and provides the reader an overview of the tools and standards adopted as well as the roles and responsibilities in CDM.