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

A study of oral Nifedipine and intravenous Labetalol in severe hypertension in pregnancy at teaching hospital

Background: Hypertensive disorders of pregnancy, including preeclampsia, complicate up to 10% of pregnancies worldwide, constituting one of the greatest causes of maternal and perinatal morbidity and mortality worldwide. Aim: To compare intravenous Labetalol with oral Nifedipine in their rapidity to control hypertensive emergencies of pregnancy. Materials and methods: Pregnant woman with severe gestational hypertension ≥ 160/110 mm of Hg were randomized to receive intravenous Labetalol injection (in an escalating dose regimen of 20, 40, 80, 80 and 80 mg) or Nifedipine (10mg tab orally upto 5 doses ) until the target blood pressure of 150/90mm of Hg was achieved. Crossover treatment was effected if the initial treatment regimen was unsuccessful. Results: Mean time required 47 ± 14 mins in the Labetalol groups and 45 ± 15minutes in the Nifedipine group. This comparison showed no difference in the two groups with a „P‟ value of >0.05. The mean amount of drugs required to achieve BP 150/90mm of Hg were 96 ± 38in the Labetalol group and 23 ± 13mg in the Nifedipine group. And this comparison showed no difference statistically with a „P‟ value of >0.05. Most of the patients were controlled by 2 doses of each drug, 56% in the Labetalol group and 62% in the Nifedipine group. 12% and 14% in the Labetalol and Nifedipine group respectively were not controlled by 5 doses of either drug and required crossover drug therapy. Most of the patients were controlled by two doses of each drug, 50% in the Labetalol group and 60% in the Nifedipine group. 12.5% and 17.5% in the Labetalol & Nifedipine group respectively were not controlled by 5 doses of either drug andrequires crossover drug therapy.

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.

Assessment of temperament in women with stress urinary incontinence: an observational study

This study aimed to explore whether the temperament of the body is related to and can cause stress uiinary incontinence [SUI] in reproductive-age women. Urinary incontinence [UI] is defined as involuntaiy loss of urine. SUIis defined as ''the complaint of involuntary leakage on effort or exertion, or on sneezing or coughing. "In Unani medicine, one of the causes that lead to UI is temperament [mizaj] of the body or organ

This study was a single-center, observational trial conducted at the outpatient department of the National Institute of Unani Medicine, Bangalore, India, between March 2012 and November 2012. A total of60 women presenting with SUI for at least 6 months, who fulfilled the inclusion criteria, were recruited Their general temperament was assessed using aprestructuredproforma designed for assessing temperament that was based on 10 deteiminants [alamat ajnase ashra]

Of 60 patients, sanguine and phlegmatic temperament was found in 31 [52%] and 29 [48%] patients, respectively. None of the patients had choleric and melancholic temperament. Maximum number of women were in the age group of31-40 years [n =38, 63%] in which 55% [n = 17] and 72% [n =21] had sanguine and phlegmatic temperament, respectively. All patients had anterior vaginal wall prolapsed

It is concluded that SUI occurs in reproductive-age women with sanguine and phlegmatic temperament. Also, using objective parameters for temperament assessment and conducting randomized studies with a larger sample size are recommended

Clinical evaluation and investigations in women with stress urinary incontinence: an overview

Urinary incontinence [UI]is defined as the complaint of any in voluntary loss of urine. Ulcan be slightly bothersome or totally debilitating. For some women, the risk of public embarrassment prevents them from enjoying many activities with their family and fi'iends. Women are four times more likely to be affected by Uf compared with men. Stress urinary incontinence [SUI] is the most common type ofUIin women below age 60 and accounts for almost 50% of incontinence in all women. The minimum evaluation in women with symptoms of uncomplicated SUI includes history, urinalysis, physical examination, assessment of urethral mobility, demonstration of SUI, and measurement ofpostvoid residual urine volume. Additional diagnostic evaluation with multichannel urodynamic testing is helpful in women with complicated SUI, especially before surgical treatment. Clinical decision should help the health care providers to perfoim preoperative multichannel urodynamic testing or refer to an expert in umlogy who is skilled in female pelvic medicine and reconstructive surgery

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 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.

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.

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.

Evaluation of anti-inflammatory activity of root bark of clerodendrum phlomidis in experimental models of inflammation.

The study was carried out to evaluate anti-inflammatory activity of aqueous extract of root bark of Clerodendrum phlomidis (CP) in models of acute and chronic inflammation in rats. Anti-inflammatory activity of CP was evaluated in models of acute inflammation viz. carrageenan induced rat paw oedema and acetic acid induced peritonitis in mice. The anti-inflammatory activity against chronic inflammation was assessed in model of cotton pellet granuloma in rats. The activity of CP was compared with aspirin and Dashamoolarishta (a multi-ingredient plant formulation containing Clerodendrum phlomidis) which served as positive controls. CP in the dose of 21.6 ml/kg showed significant anti-inflammatory activity (15.85 % inhibition in the carrageenan model and 50.38% inhibition in the model of chronic inflammation). In the peritonitis model, the maximum anti-inflammatory activity (27.32% inhibition was seen with the corresponding dose in mice. The present study demonstrates anti-inflammatory activity of aqueous extract of root bark of CP and also provides a scientific basis for inclusion of CP in the Dashamoolarishta formulation.