Yashashri C Shetty

Knowledge, attitude, and practices toward ayurvedic medicine use among allopathic resident doctors: A cross-sectional study at a tertiary care hospital in India.

Context: Ayurveda is most commonly practiced form of complementary and alternative medicine (CAM) in India. There are very few studies showing the knowledge, attitude, and practices (KAP) of allopathic doctors about Ayurvedic drugs and its use. Aims: The study was initiated to assess KAP toward Ayurvedic medicine use among allopathic resident doctors. Settings and Design: Cross-sectional and prospective study. Materials and Methods: After obtaining permission from the Institutional Ethics Committee, allopathic resident doctors from clinical departments were approached personally. They were given pre-formed validated questionnaire to assess KAP toward Ayurvedic medicine use. Statistical Analysis Used: Descriptive statistics. Results: Allopathic residents had little knowledge about basic concepts of Ayurveda, that is, ‘panchakarma’ and ‘tridosha’. Majority residents (99%) had no opportunity to learn basics of Ayurveda, but 67% residents prescribed Ayurvedic medicines to patients. However, many residents (76%) mentioned that cross practice should not be allowed due to lack of knowledge. One resident knew that cross-practice was not allowed by law. The commonly prescribed proprietary Ayurvedic medicines were Liv-52 (39%), Shatavari (13%), Cystone (12%) and common ailments for which these medicines prescribed were liver disorders (34%), arthritis (18%), cough and cold (13%), kidney stones (11%), and piles (10%). Nearly 76% residents felt incorporation of Ayurveda with modern medicine would attract more patients and at the same time most residents (92%) agreed that Ayurvedic medicines need scientific testing before use. Though 50% of the residents agreed for voluntary training in Ayurveda, 80% denied compulsory training. Nearly 63% residents recommended Ayurveda among all CAMs. Most of residents heard of Ayurveda from their colleagues. Conclusions: This study reveals that allopathic resident doctors had little knowledge about Ayurveda and Ayurvedic medicine use but engaged in prescription of Ayurvedic medicines. So some interventions should be taken to increase the knowledge and awareness of allopathic resident doctors about Ayurvedic medicine use.

Analysis of warning letters issued by the US Food and Drug Administration to clinical investigators, institutional review boards and sponsors: a retrospective study

The US Food and Drug Administration (FDA) issues warning letters to all research stakeholders if unacceptable deficiencies are found during site visits. Warning letters issued by the FDA between January 2011 and December 2012 to clinical investigators and institutional review boards (IRBs) were reviewed for various violation themes and compared to similar studies in the past. Warning letters issued to sponsors between January 2005 and December 2012 were analysed for the first time for a specific set of violations using descriptive statistics. Failure to protect subject safety and to report adverse events to IRBs was found to be significant compared to prior studies for clinical investigators, while failure to follow standard operating procedures and maintain documentation was noted as significant in warning letters to IRBs. Failure to maintain minutes of meeting and to follow written procedures for continuing review were new substantial violations in warning letters issued to IRBs. Forty-six warning letters were issued to sponsors, the most common violations being failure to follow a monitoring schedule (58.69%), failure to obtain investigator agreement (34.78%), failure to secure investigators’ compliance (30.43%), and failure to maintain data records and ship documents to investigators (30.43%). Appropriate methods for handling clinical trial procedural violations should be developed and implemented worldwide.

Introduction of case based teaching to impart rational pharmacotherapy skills in undergraduate medical students

Objective: The aim of this study is to assess the impact of case based teaching (CBT) on learning rational prescribing and to compare CBT with the traditional method of teaching (TRD). Materials and Methods: Second year Bachelor of Medicine and Bachelor of Surgery (MBBS) students (n = 179) were administered a pre-test and randomly divided into groups to receive CBT (n = 96) and TRD (n = 83). CBT group was further sub-divided into CBT1 and CBT2. Both these groups were taught two topics each by CBT and TRD during tutorials; however, the topics were switched with respect to method of teaching. The post-test comprised of three therapeutic problems of which two were related, and one was not related to the tutorial topics. Marks obtained in the post-test were graded and analysed using Fischers exact test. Results: In the post-test, the therapeutic problems on diabetes mellitus and peptic ulcer were attempted by 85.41% students from CBT and 73.49% from TRD group. CBT group obtained more marks for these problems (4.23 ± 0.94; P < 0.001) than the TRD (3.32 ± 0.92) group. Also, more students in the CBT obtained grade 3 (P < 0.001) and fewer obtained grade 1 (P < 0.01), compared to the TRD group. When the grades of the two CBT groups were compared, it was found that fewer students in CBT 2 had obtained grade 1 and those scoring higher grades were comparable between the two groups. For the therapeutic problem on malaria, 7.29% students from CBT and 18.07% from TRD received 0 grade (P < 0.05). More students received ≥ 2 grade in CBT group (P < 0.05). Conclusion: Use of CBT during tutorials is better than TRD and facilitates learning of rational pharmacotherapy.

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

Abstract 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.

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.

Is Coercion Involved in the Decision-Making of Medical Students Participating in Research?: A Cross-Sectional Study

Introduction: Autonomy has been the most frequently compromised ethical principle in research involving human subjects. Even medical students are vulnerable when requests for research participation come from faculty members. The present study was designed to find out if coercion is involved in the decision-making of medical students participating in research.Methods: Ethics committee approval was obtained and 300 medical students were administered a validated questionnaire, after obtaining their written informed consent. The questionnaire contained questions on motives for participation, coercion assessment scale and recruitment scenarios. The responses were analysed using descriptive statistics.Results: Of the 300 medical students, 65% (195/300) had participated in <3 and 35% (105/300) had participated in ≥3 research studies. 71% (213/300) had participated in questionnaire-based studies, 21% (63/300) in interventional studies and 8% (24/300) in other observational studies. Among those who participated in <3 studies, 32% (62/195) stated scientific interest as the primary reason for participation whereas 31% (61/195) participated mainly because their participation was requested by a faculty member. An analysis of the coercion assessment scale revealed that 35% (105/300) of students said that participation in the study was not entirely of their own choice and 61% (183/300) said that they participated in the study even though they did not want to. 55% (165/300) thought that their professor would like them to participate and 57% (171/300) felt that the professor would be displeased if they did not participate. Among those who participated in <3 studies, 64% (125/195) said they thought that they could not refuse to participate. 74% (77/105) of those participating in ≥3 studies felt that the participation would help their academic grades. 84% (252/300) said that sufficient time was given to read the consent document and 86% (258/300) stated that they would participate in similar research studies in future.Conclusion: The results suggest the presence of potential coercion on medical students to participate in research. Also the students were not aware of the subtle coercive influences that can occur during recruitment. Educating medical students and faculty on appropriate recruitment procedures and a careful review of the same by the Institutional Ethics Committees would help to remove these coercive influences and ensure the autonomy of medical students participating in research studies.

Evaluation of oral multi-herbal preparation of Dashmoolarishta on mice model of osteoarthritis

Abstract Background: Osteoarthritis (OA) is a chronic progressive disease commonly affecting the hip and knee joints. Although synthetic drugs are available and afford symptomatic relief, their side effects pose limitations to their continuous use. So, this research was focused on extracting drugs from indigenous medicinal plants that could have a beneficial effect on osteoarthritis. Dashmoolarishta is one such preparation whose effects have never been studied in comparison with recent drugs like hyaluronic acid (HA), hence this particular study was undertaken. The aim of this study was to evaluate the effects of Dashmoolarishta compared with HA on joint pathology and pain behavior in monosodiumiodoacetate (MIA)-induced OA in experimental mice. Methods: The study was initiated after obtaining permission from the Animal Ethics Committee. This study was based on the MIA model of osteoarthritis, with mice being divided into five groups viz.: disease control (DC), Dasahmoolarishta high dose (HD) and low dose (LD), sham control (SC) and HA. The OA of the knee joint was induced in these mice using monosodiumiodoacetate. Seven days after induction, animals were subjected to weekly behavioral tests, daily oral Dashmoolarishta, and biweekly HA administration from weeks 2–4. At the end of the 4th week, histopathological examination of the knee joints was done. Results: DC showed significant osteoarthritic changes. At week 4, the behavioral tests and histopathology results of all groups were found to be significant. A significant difference (p<0.05) was found between DC vs. SC, HA, HD, LD for open field test, Rota rod test, knee joint diameter, and Cat walk test. Dashmoolarishta HD and LD showed significant improvement in pain, as assessed by behavioral tests (p<0.05) and pathology, as assessed by knee joint histopathology (p<0.05). Conclusions: Oral Dashmoolarishta showed reduction in pain and disease activity in MIA-induced osteoarthritis in mice model.

Are institutional review boards prepared for active continuing review

Continuing review is an important responsibility of Institutional Review Boards (IRBs). Though being mentioned by many of the national and international guidelines, it is carried out routinely only in UK. The reasons may be inadequate training, overworked IRBs, less enthusiasm among the IRB members, cost bearing, etc. So, the oversight mechanism at the local site, which is the responsibility of IRB is not fulfilled. Are there any solutions to overcome these difficulties? The IRBs should have a Standard operating procedure for continuing review, members can be regularly trained, institutions can create their own internal Data and Safety Monitoring Boards who will only monitor studies where monitoring systems are non-existing and there can be budget allocated at the start of the study by the sponsor or the institution. In this way, we can try to safeguard the rights and well-being of the study participants.

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.

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.