Perceptions and experiences of community members serving on institutional review boards: a questionnaire based study.

The community representative plays a very important role in an institutional review board (IRB) but there is sparse data about their understanding of their role in an IRB. This study was conducted to assess perceptions of community members serving on IRBs of one region in India. A validated questionnaire (Cohen's kappa coefficient of 0.84) was administered to community members of IRBs in a prospective cross-sectional study. The questions related to demography, perceptions of their role in the IRB, experiences while serving on the IRBs, difficulties faced by them, and suggestions to improve their contributions. Of the 56 IRBs contacted, all 15 of the public institutions shared details of their community members, while only 26 of the 41 IRBs of private institutions responded. When questioned about why they joined the IRB, one third of the respondents said either that there was "no specific reason" for joining or that they accepted the invitation to serve on the insistence of other members of the IRBs or the head of their institution. All except one felt that community members were needed for optimal functioning. Six participants said that they did not review informed consent documents (ICD), and 10 were unaware that their presence was vital for quorum to be met. Twenty-eight said they participated actively in meetings and did not feel intimidated by the presence of clinicians. Twelve reported difficulties in understanding medical terminologies in ICDs. Although the majority of participants were aware about their role in an IRB, some did not review important documents such as ICDs. Restricted participation by private hospital IRBs was a striking observation in our study. There is a need to define eligibility criteria and develop targeted training modules for community members to ensure their effective contribution to effective oversight of clinical research.

Animal models of erectile dysfunction.

Animal models have contributed to a great extent to understanding and advancement in the field of sexual medicine. Many current medical and surgical therapies in sexual medicine have been tried based on these animal models. Extensive literature search revealed that the compiled information is limited. In this review, we describe various experimental models of erectile dysfunction (ED) encompassing their procedures, variables of assessment, advantages and disadvantages. The search strategy consisted of review of PubMed based articles. We included original research work and certain review articles available in PubMed database. The search terms used were "ED and experimental models," "ED and nervous stimulation," "ED and cavernous nerve stimulation," "ED and central stimulation," "ED and diabetes mellitus," "ED and ageing," "ED and hypercholesteremia," "ED and Peyronie's disease," "radiation induced ED," "telemetric recording," "ED and mating test" and "ED and non-contact erection test."

Role of dopamine--D2 receptor in spatial memory retention and retrieval determined using Hebb-Williams complex maze.

Effects of bromocriptine and sulpiride were observed on encoding and retrieval of spatial memory in Wistar rats using Hebb-Williams complex maze. Rat was placed in entry chamber and allowed to reach reward chamber. Ten trials were given each day per rat for 3 consecutive days. Within-day encoding score indicative of learning and between-day retrieval score indicative of memory were calculated. Effects of bromocriptine and sulpiride were observed on encoding and retrieval of spatial memory. General learning index was calculated to compare the effect on spatial memory between groups. Bromocriptine increased while sulpiride decreased within-day encoding index but had no effect on retrieval index. In general learning index, sulpiride group showed more errors whereas bromocriptine group did not show any difference as compared to control. These results suggest that dopamine D2 receptors are involved in memory encoding but not retrieval. Also general learning is under positive modulation by D2 receptors.

A Retrospective Study of Ethics Committee Monitoring Checklists of the Audiovisual Consent Process: An Ethical Perspective.

Clinical trial regulations for new drugs in India released a gazette notification for obtaining audiovisual (AV) consent from all trial participants in November 2013. The reports of AV recordings of the studies from October 2013 to February 2017 submitted to the institutional ethics committee were analyzed in view of the Indian regulations on AV consenting. The reports of AV recording were checked: number of AV consents for each project, adequacy of AV recording, number of persons in the video, informed consent document elements (ICD) covered as per Schedule Y, confirmation of understanding by the participant, the time taken to complete the procedure, maintenance of confidentiality, and whether reconsent was taken. Seven studies of AV consent were monitored. Eighty-five (85) AV-consented and filled checklists were evaluated. The AV recording was not clear in 31/85, ICD elements were missing in 49/85 consents, time taken to complete the procedure was 20.03 ± 10.83 with the number of pages being 14.24 ± 7.52 (R= 0.29 p<0.041). In 19/85 consents, privacy was not maintained and on 22 occasions, reconsent were taken. There were deficits found in the AV consent process.

Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation.

Post-traumatic stress disorder (PTSD), characterized by abnormally persistent and distressing memories, is a chronic debilitating condition in need of new treatment options. Current treatment guidelines recommend psychotherapy as first line management with only two drugs, sertraline and paroxetine, approved by U.S. Food and Drug Administration (FDA) for treatment of PTSD. These drugs have limited efficacy as they only reduce symptoms related to depression and anxiety without producing permanent remission. PTSD remains a significant public health problem with high morbidity and mortality requiring major advances in therapeutics. Early evidence has emerged for the beneficial effects of psychedelics particularly in combination with psychotherapy for management of PTSD, including psilocybin, MDMA, LSD, cannabinoids, ayahuasca and ketamine. MDMA and psilocybin reduce barrier to therapy by increasing trust between therapist and patient, thus allowing for modification of trauma related memories. Furthermore, research into the memory reconsolidation mechanisms has allowed for identification of various pharmacological targets to disrupt abnormally persistent memories. A number of pre-clinical and clinical studies have investigated novel and re-purposed pharmacological agents to disrupt fear memory in PTSD. Novel therapeutic approaches like neuropeptide Y, oxytocin, cannabinoids and neuroactive steroids have also shown potential for PTSD treatment. Here, we focus on the role of fear memory in the pathophysiology of PTSD and propose that many of these new therapeutic strategies produce benefits through the effect on fear memory. Evaluation of recent research findings suggests that while a number of drugs have shown promising results in preclinical studies and pilot clinical trials, the evidence from large scale clinical trials would be needed for these drugs to be incorporated in clinical practice.

Use of Topical Steroids in Dermatology: A Questionnaire Based Study.

CONTEXT: Topical steroids, the most widely prescribed drugs in dermatology are being increasingly misused. AIMS: This study was conducted to assess knowledge and practices regarding the use of topical steroids and to analyze prescriptions containing topical steroids. SUBJECTS AND METHODS: Following approval from the institutional ethics committee, participants were recruited as per the selection criteria and divided into those treated in the institution and those having outside prescription. They were administered a pre-validated questionnaire to assess knowledge and practices regarding the use of topical steroids. STATISTICAL ANALYSIS USED: Comparison of awareness between two patient categories was done using Chi-square test. Prescription variables were analyzed using descriptive statistics. Significance of P value was set at 0.05. RESULTS: Out of 400 patients, 167 had external prescriptions whereas 233 were institutional patients. Only 5.5% of all patients knew about the type of drug prescribed whereas 31.25% were aware of the indication. A total of 33.75% of the patients knew topical steroids required a prescription and 5.6% said they were aware that topical steroid use was associated with side effects. Side effects were reported by 96 patients. Awareness regarding knowledge, indication, and need for prescription were significantly better in institutional patients whereas knowledge about side effects was lacking in both groups. Psoriasis was the most common indication overall whereas tinea was the most common indication (51.5%) among externally prescribed. CONCLUSIONS: Although this study showed that institutional patients had comparatively better knowledge than community-treated patients, there is a need to create more awareness among patients overall and implement measures to stop irrational prescribing practices in the community.

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.

Payment for participation in clinical research: Review of proposals submitted to the ethics committees.

OBJECTIVE: In view of dearth of information in national and international guidelines on payment practices in research, the present study was done to find out payments for participation allowed by 3 Ethics committees (ECs) and reasons for payment. METHOD: This was a retrospective observational study which analysed research proposals reviewed by 2 institutional and 1 non-institutional ECs over a period of 2 years. The permission of ECs was obtained and confidentiality of data was maintained. RESULTS: Of the 73 studies requiring payment, 89.04% were interventional and 10.96% observational. Reimbursement of travel expenses (60%) was the major reason for payment followed by inconvenience due to participation, loss of wages and time spent. The queries raised by EC in more than 50 % of studies were related to informing patients about the payment in the informed consent document. The investigators complied with the EC requirements regarding payment (15/21) and the remaining provided explanations. The median amount of payment in pharmaceutical sponsored studies was higher compared to investigator initiated studies. Higher payments were approved by ECs on case to case basis in a few studies. The ECs did not have any policy/ standard operating procedure for payment practices. CONCLUSION: The present study first of its kind in India, demonstrated that quantum of payment was not uniform for pharmaceutical sponsored and investigator initiated studies and payments were not considered for majority of observational studies. Travel reimbursement was the most common reason for payment. There is a need to develop guidelines for determining appropriate payment/incentives to participants for specific types of research related activities.

Ethics Committees in India: Past, present and future.

Following watershed amendments in Schedule Y India's star rose rather rapidly on the clinical research (especially clinical trials) horizon. Just as dramatic was the fall of this empire. At the centre of these events has been the participant and indirectly, the Ethics Committee (EC) that is established primarily to protect this individual. This paper traces the evolution of the concept of ECs in India, examines the current state of these committees in the country and suggests the way forward. THE PAST: The requirement for an EC to oversee clinical research was first made in the ICMR Policy Statement for Ethics published in 1980 and then again in the Schedule Y (1988). Later, both the Amended Schedule Y (2005) assigned regulatory responsibility on the EC and the ICMR Guidelines (2006) described the functioning of ECs. Several challenges including inadequate formal training, contribution from non-technical members, administrative support as well no SOPs and a heavy workload were identified. In the absence of regulatory oversight of ECs, the introduction of the Clinical Trial Registry - India (CTRI) and self-regulation through voluntary accreditation programs brought a measure of accountability and transparency. THE PRESENT: A slew of regulatory reforms led to more than 1000 ECs to be registered with CDSCO although the actual impact on participants' protection and safety of these new regulations still remains to be seen. WAY FORWARD: A method to oversee all ECs, improved functioning of ECs including on site monitoring, central ECs for multicentric studies, the development of metrics to assess the ability of ECs to protect the participant are other ideas for the future. CONCLUSIONS: Although ECs in India have evolved from being mere rubber stamps for approval of protocols to efficiently functioning accredited ECs, yet there is much to be done for and by Ethics Committees.

Serious Adverse Events Reports: Analysis and Outcome of Review by an Institutional Ethics Committee of a Tertiary Care Hospital in Mumbai, India.

The Indian regulations for clinical trials were amended in January 2013 regarding reporting time lines, relatedness, and compensation for Serious Adverse Events (SAEs). Our study assessed the extent of regulatory compliance in reporting SAEs to the Institutional Ethics Committee (IEC) over 4 years (January 2009-January 2013) before and 18 months after (February 2013-July 2014) the amended regulations. SAE reports were studied retrospectively for reporting time lines, relatedness, compensation, and IEC response before and after the law revision. Before 2013 had 89/160 (55.6%) SAEs reports submitted late while in the after period, only 2/11 reports were delayed (18%). In the before period, 26 SAE reports mentioned "relatedness" of which only 15 (57.6%) stated about compensation. After 2013, all the 9 non-death reports were complete. The IEC took median 17 days to respond before 2013, while after 2013 responded within 5 days. Thus, there was poor compliance in terms of SAE reporting time lines before the revision of the law.

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.

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.

Effect of Jyotismati seed oil on spatial and fear memory using scopolamine induced amnesia in mice.

BACKGROUND: Treatment of memory impairment associated with dementia such as Alzheimer's disease is still inadequate and requires development of new drugs. OBJECTIVE: The objective was to evaluate the memory enhancing effect of Celastrus paniculatus seed oil. MATERIALS AND METHODS: C. paniculatus seed oil was mixed with equal amount of pure ghee and administered orally to mice in the dose of 200 mg/kg/day. Piracetam was used as a standard nootropic. Elevated plus maze and passive avoidance tests were used as a models to test spatial and fear memory respectively. Scopolamine (3 mg/kg, i.p.), was used as an amnestic agent. RESULTS: Mice receiving C. paniculatus showed significant memory enhancement as compared to scopolamine group. The effect of C. paniculatus and combination of C. paniculatus with piracetam was comparable to that with piracetam alone. CONCLUSION: The present study demonstrates that C. paniculatus seed oil has memory enhancing effect and hence can be developed as a potential drug in the treatment of dementia.

Experimental evaluation of analgesic, anti-inflammatory and anti-platelet potential of Dashamoola.

BACKGROUND: Dashamoola, in the form of arishta and kwath, is a commonly used classical Ayurvedic multi-ingredient formulation for management of pain, arthritis and inflammatory disorders. OBJECTIVE: To study analgesic, anti-inflammatory and anti-platelet activity of Dashamoola and its combination with aspirin. MATERIALS AND METHODS: Wistar albino rats (180-200 g) and Swiss albino mice (20-25 g) of either sex were divided randomly into five groups: Distilled water, aspirin (500mg/kg in rats; 722.2 mg/kg in mice), Dashamoolarishta (1.8 mL/kg in rats; 2.5 mL/kg in mice) and Dashamoolarishta with aspirin. Anti-inflammatory activity was measured by change in paw volume in carrageenan-induced inflammation, protein content in model of peritonitis and granuloma weight in cotton pellet granuloma. Analgesic effect was evaluated by counting number of writhes in writhing model. Maximum platelet aggregation and percentage inhibition of ADP and collagen-induced platelet aggregation were estimated in vitro. Statistical analysis was done using one way ANOVA (post hoc Tukey's test) and P < 0.05 was considered significant. RESULTS: Dashamoolarishta and its combination with aspirin showed significantly (P < 0.01) less number of writhes. It showed significant (P < 0.001) anti-inflammatory activity by paw edema reduction in rats, decrease in proteins in peritoneal fluid (P < 0.001) and decrease in granuloma weight (P < 0.05) as compared to respective vehicle control groups. Dashamoola kwath alone and in combination with aspirin inhibited maximum platelet aggregation and percent inhibition of platelets as compared to vehicle (P < 0.001). CONCLUSION: Dashamoola formulation alone and its combination with aspirin showed comparable anti-inflammatory, analgesic and anti-platelet effects to aspirin.

Effect of Saraswatarishta in animal models of behavior despair.

BACKGROUND: Saraswatarishta (SA) is a herbo-mineral formulation consisting of 18 plants some of which are Medhyarasayanas. It has been claimed to be useful in treating central nervous system disorders. OBJECTIVE: To evaluate antidepressant effect of 'Saraswatarishta'(SA) alone and in combination with imipramine and fluoxetine in animal models of depression. MATERIALS AND METHODS: After obtaining IAEC permission, 144 rats (n = 36/part) were randomized into 6 groups- Group 1: Distilled water (1 mL), Group 2: Imipramine (30 mg/kg), Group 3: Fluoxetine (10 mg/kg), Group 4: SA (1.8 mL/kg), Group 5: Imipramine + SA, Group 6: Fluoxetine + SA. Effects of study drugs were evaluated in forced swim test (FST) with single exposure to FST (Part 1) and repeated exposure for 14 days (Part 2). In Part 3, reserpine was used with FST and effects of study drugs were evaluated against single exposure to FST. Same model was used with repeated exposures to FST (Part 4). In each part, rats were subjected to open field test (OFT) for 5 min prior to final FST. The variables measured: Immobility time in FST; line crossing, rearing and defecation in the OFT. RESULTS: In all four parts, individual drugs and combinations thereof produced significant decrease in immobility time as compared to control, and extent of decrease was comparable amongst these groups. However, values for combination of fluoxetine with SA group were found to be lesser than that for individual agents in Parts 2 and 3. Combination of SA with imipramine did not enhance its anti-depressant effect in any of the parts. OFT findings did not vary significantly amongst the study groups. CONCLUSION: Decreased immobility in FST and absence of generalized stimulation or depression of motor activity in OFT point towards potential antidepressant effect of Saraswatarishta. Its co-administration with fluoxetine showed more promising effects.

Effect of combination of Phyllanthus emblica, Tinospora cordifolia, and Ocimum sanctum on spatial learning and memory in rats.

BACKGROUND: There has been a steady rise in number of patients suffering from dementia including dementia associated with Alzheimer's disease. Effective treatment of Alzheimer's disease dementia is an unmet medical need. OBJECTIVE: To evaluate effects of formulation containing combination of Phyllanthus emblica (Pe) and Tinospora cordifolia (Tc) with and without Ocimum sanctum (Os) on learning and memory performance of normal and memory impaired rats in complex maze and compare with effects of Tinospora cordifolia and Phyllanthus emblica alone. MATERIALS AND METHODS: Wistar rats; either sex (100-150 g) were divided in seven groups Control, Piracetam, Rivastigmine, Tc, Pe, Formulation 1 (Tc + Pe), and Formulation 2 (Tc + Pe + Os). The study was divided in four parts: In part 1 memory enhancement was tested in normal rats. In part 2, 3, and 4 the effects of drugs were tested in Scopolamine-, Diazepam-, and Cyclosporine-induced amnesia. Hebb-Williams maze was used to test for learning and memory. Time required to trace food and number of errors in maze were noted. RESULTS: In normal rats, all test drugs showed significant reduction in time required to trace the food and number of errors after 24 h compared with vehicle control. Formulations 1 and 2 reduced the time required to trace food and number of errors and the results were comparable with positive control groups and comparators Tc and Pe. Formulations 1 and 2 reversed amnesia produced by Scopolamine, Diazepam, and Cyclosporine when compared with vehicle control and showed comparable results with those of positive control groups and comparators Tc and Pe. CONCLUSION: Formulations 1 and 2 demonstrated nootropic activity and both the formulations showed comparable nootropic activity with that of Tc and Pe alone.

Awareness about medical research among resident doctors in a tertiary care hospital: A cross-sectional survey.

CONTEXT: Every medical practitioner should strive to contribute to the generation of evidence by conducting research. For carrying out research, adequate knowledge, practical skills, and development of the right attitude are crucial. A literature review shows that data regarding knowledge, attitude, and practices toward medical research, among resident doctors in India, is lacking. AIMS: This study was conducted to assess research-related knowledge, attitude, and practices among resident doctors. SETTINGS AND DESIGN: A cross-sectional survey was conducted using a pretested, structured, and pre-validated questionnaire. MATERIALS AND METHODS: With approval of the Institutional Ethics Committee and a verbal consent, a cross-sectional survey among 100 resident doctors pursuing their second and third years in the MD and MS courses was conducted using a structured and pre-validated questionnaire. STATISTICAL ANALYSIS: Descriptive statistics were used to analyze the results. RESULTS: The concept of research hypothesis was known to 58% of the residents. Ninety-eight percent of the residents were aware of the procedure to obtain informed consent. Seventy-six percent agreed that research training should be mandatory. Although 88% of the residents were interested in conducting research in future, 50% had participated in research other than a dissertation project, 28% had made scientific presentations, and only 4% had publications. Lack of time (74%), lack of research curriculum (42%), and inadequate facilities (38%) were stated as major obstacles for pursuing research. CONCLUSIONS: Although resident doctors demonstrated a fairly good knowledge and positive attitude toward research, it did not translate into practice for most of them. There is a need to improve the existing medical education system to foster research culture among resident doctors.

A study to assess completeness of project application forms submitted to Institutional Ethics Committees (IEC) of a tertiary care hospital.

OBJECTIVES: To review Ethics Committee (EC) application forms and to find out similarities and differences in content of five ECs forms in India. MATERIALS AND METHODS: THE COMPLETENESS OF EC APPLICATION FORMS WAS ASSESSED ON THE FOLLOWING THEMES: title, study team, sponsor responsibility, scientific aspects, patient safety, regulatory permissions, Informed consent process from 2008-2009. Application forms (available online) of 5 ECs were studied and compared. RESULTS: A total of 445 application forms were analyzed, 382 were academic, 63 were sponsored. The common deficiencies in academic studies were inappropriate titles (25.13%), lack of budget details (90%). More than 95% studies had not mentioned the method of recruitment. The issue of vulnerability was not marked in more than 50% of studies. Compensation for participation/injury was poorly stated in academic (99%) studies. Among industry sponsored studies, 98% were compliant with regulatory permissions and 41% were CTRI registered. The information pertaining to Informed Consent was mentioned in all forms. Comparative analysis of application forms of 5 ECs showed that the requirements for submission were similar except 1-2 ECs asked for additional information like percentage of time allotted by investigator for studies, GCP training of study team, certification by investigator regarding accuracy of local versions of Informed consent. CONCLUSION: Our study recommends that increased awareness and vigilance by investigators of academic studies regarding submission of applications to EC will increase efficiency and speed of review process. A common application form for all ECs across India would be an important step to achieve uniformity in functioning of ethics committees.