A critical analysis of the COMPASS trial with respect to benefit-risk assessment using the numbers needed to treat: Applicability and relevance in Indian patients with stable cardiovascular disease

The recently published Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial evaluated the hypothesis that rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary prevention. In India, stable cardiovascular disease occurs in a much younger age group relative to the rest of the world. Our critical analysis of COMPASS trial showed that the younger age group appeared to derive greater benefit from the rivaroxaban + aspirin combination (relative to aspirin alone) as seen with number needed to treat metrics as compared to the older age group.

Demographics of animal bite victims & management practices in a tertiary care institute in Mumbai, Maharashtra, India.

Background & objectives: Rabies is an important public health problem worldwide and more than 55,000 people die annually of the disease. The King Edward Memorial Hospital, Mumbai, is a tertiary referral centre where a rabies clinic runs 24 hours. In view of lack of information about the demographics of the disease in an urban environment the present study was carried out. Methods: Data on 1000 consecutive animal bite victims presenting to the institute in 2010 were collected over a 15 wk period. An electronic database was specially created for capturing information and was modelled on the information available from the WHO expert consultation on rabies, 2005. Economic burden from the patients’ perspective was calculated using both direct and indirect costs. Results: The victims were largely males (771 subjects). The dog was the major biting animal (891, 89.1%).Bites were mainly of Category III (783, 78.3%). One twenty three subjects used indigenous treatments only for local wound care. Of the Category III bites, only 21 of 783 (2.7%) patients were prescribed human rabies immunoglobulin (HRIG) which was primarily for severe bites or bites close to or on the face. A total of 318 patients did not complete the full Essen regime of the vaccine. The median cost to the patient per bite was ` 220 (3.5 USD). Interpretation & conclusions: Our findings showed that the use of HRIG was low with less than 2 per cent of the Category III patients being prescribed it. As vaccine and HRIG continue to remain expensive, the intradermal vaccine, shorter regimes like the Zagreb regime and monoclonal antibodies may offer safer and cost-effective options in the future. Further studies need to be done in different parts of the country.

Use of and satisfaction with complementary and alternative medicine in four chronic diseases: A cross-sectional study from India.

Background. We assessed the extent of use of complementary and alternative medicine (CAM) by patients with four chronic diseases—epilepsy, HIV, rheumatoid arthritis (RA) and diabetes mellitus (DM)—at a tertiary care, teaching hospital of allopathic medicine in India. We also assessed patients’ satisfaction with CAM. Methods. Adults attending the outpatient clinics for epilepsy, HIV, RA and DM who took CAM were recruited over a period of 16 weeks. After obtaining written informed consent, they were administered the ‘Treatment Satisfaction Questionnaire for Medication’ (TSQM)TM to assess satisfaction in domains such as effectiveness, no side-effect, convenience and global satisfaction. Results. Of the 4664 patients screened, 1619 (34.7%) were using CAM and 650 (40%) of them consented to participate. The extent of use of CAM was 63% in patients with DM, 42.7% in RA, 26.2% in HIV and 7.7% in epilepsy. Ayurveda 57.1% (95% CI 53.27–60.89) was the most frequently used CAM. Satisfaction in terms of effectiveness and global satisfaction was highest among patients with HIV (69.4% and 69.2%, respectively) and least among those who had RA (56.6% and 54.1%, respectively). High scores were reported to ‘no side-effect’ domain in all the four diseases. The proportion of physicians who were aware about their patients’ using CAM was 100% in patients with RA, 95% in HIV, 74% in epilepsy and 29% in DM. Conclusion. A large proportion of patients with four chronic diseases reporting to a hospital of allopathic medicine in India were also using CAM and were satisfied with its use. Given the potential interaction of CAM with allopathic medicines, a history of use of CAM should be elicited in clinical practice.

Use of the WOMAC questionnaire in Mumbai and the challenges of translation and cross cultural adaptation.

Patient-reported outcome measures (PROMs) are disease specific questionnaires that are being increasingly used in clinical practice and research. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), is a widely used PROM in patients with hip or knee osteoarthritis. A validated WOMAC was used by us, and significant challenges were faced in administering it as several questions did not have a cultural connect. Functionally equivalent items in the Indian context had then to be used to complete the score.

Frequency and causes for exclusion from randomization of healthy volunteers screened for a phase 1 study in India.

Background. Only a proportion of screened potential participants were actually randomized while conducting a phase 1 study of a humanized rabies monoclonal antibody. We aimed to assess the challenges in defining who is a normal volunteer and the issues that affect volunteer recruitment and thus accrual. Methods. One hundred and fifty-six volunteers were screened and 74 (47.4%) were randomized in a phase 1 study. Data on all participants screened for the study were analysed and reasons for their non-randomization were classified. Results. The reasons for volunteers not being randomized were: (i) deranged laboratory parameters (n=62); (ii) nonlaboratory causes (n=4); and (iii) withdrawal of consent (n=16). A large proportion of screen failures were due to low haemoglobin levels, which led to the protocol being amended midway during the study. An informal interview of those who declined consent showed that they had only wanted to get themselves investigated thoroughly or were interested in getting their HIV status evaluated. Conclusions. Our study shows that <50% participants screened for a phase 1 study in a developing country actually get randomized. The main reason for non-randomization is abnormal laboratory tests. This may help investigators and sponsors to plan protocols better, define normal ranges with acceptable variations based on their own populations a priori and have more pragmatic accrual targets.

Post-marketing study to assess the safety, tolerability and effectiveness of Fungisome: an Indian liposomal amphotericin B preparation.

BACKGROUND: In May 2003, an indigenously developed liposomal amphotericin B (Fungisome) was introduced in the Indian market for the treatment of systemic fungal infections and visceral leishmaniasis. The present post marketing study assessed the safety and effectiveness of Fungisome in actual clinical practice. Setting and Design: Retrospective post marketing surveillance from four cities of India. METHODS: The present study was carried out for a period of 6 months (Jun-Nov 2004), a year after the introduction of the drug. A list of doctors who had prescribed and procured the drug was obtained from the distributor. Consent to participate and scrutinize the patients' source notes were obtained from the concerned doctors. All patients who had received Fungisome treatment were included. Data was collected from the patient's source notes on a predesigned proforma. They were then analyzed by descriptive statistics. Cost of Fungisome was calculated on the basis of dose used and number of days of treatment. RESULTS: Data were available for 109/144 patients from 35/40 physicians. Fungisome was administered at 1-3 mg/kg/day for 7-76 days. No serious adverse events related to the drug were observed in the study. Mild infusion-related adverse events were reported in 40 (36%), moderate in 11 (10%) of patients and severe in 2 (1.8%). None of the adverse events were certain to Fungisome exposure, 12 (11%) were probable, 28 (25 %) were possible, and 13 (11.9%) were unlikely. Of the 91 assessable patients (received at least eight doses of Fungisome) for efficacy complete response was observed in 67 (73.6%), 16 (17.5%) had partial responses, and 8 (8.7%) of patients had no response. The acquisition cost per day and per course treatment of different fungal infections ranged from (apprx) Rs 4500-8000 and 0.9-2.1 lakh respectively. CONCLUSION: This postmarketing study documents the safety, tolerability, effectiveness and cost advantage of indigenously developed liposomal amphotericin B in the treatment of systemic fungal infections and febrile neutropenia in actual clinical practice.