Clinical research in India: Great expectations?

India is considered as a preferred site for conducting global clinical trials. Existence of a large treatment-naοve population, availability of English-speaking, skilled doctors, plenty of clinical material, and cost-savings are obvious advantages for carrying out clinical research in India. However, challenges exist at various levels. Lack of formal training in bioethics and research methodology, heavy burden of clinical duties and sub-optimal administrative support restrict investigators. Absence of oversight of functioning of ethics committees (ECs) and lack of mechanisms for ensuring quality of ethics review heighten societal concerns about safety of participants. Conducting research on issues not relevant to local needs and failure to ensure post-trial access further enhance society′s cynicism. These issues need to be tackled through capacity building, training of investigators and EC members, strengthening of EC functioning and encouraging greater community participation

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. Keywords: Stable Coronary artery disease, Rivaroxaban, Young Indian Population, Likelihood of being helped and harme

Pharmacokinetics of rectal compared to intramuscular paracetamol in children undergoing minor surgery

Objectives : Although paracetamol is a widely accepted and safe analgesic, guidelines regarding its definite analgesic dose are lacking. This study was, therefore, undertaken to compare the pharmacokinetics of paracetamol when administered by two routes, viz, intramuscular and rectal, in children undergoing minor surgery. Design : Randomized, controlled, assessor-blind, comparative clinical trial. Materials and Methods: Following Institutional Ethics Committee approval and valid consent, children undergoing minor surgery were randomized to receive paracetamol either intramuscularly or rectally. Blood samples were collected at fixed intervals for estimation of drug levels. Results : Fifty children (43 boys, 7 girls; ages 3 to 12 years; weight 10 to 40 kg) were enrolled in the study. 26 patients were randomized to receive paracetamol intramuscularly (mean dose 14.8 ± 0.9 mg/kg) and 24 to receive the paracetamol as a rectal suppository (mean dose 29.5 ± 1.4 mg/kg). Complete pharmacokinetic analysis was possible in only 29 patients, as the blood samples of the others were either not received or were inadequate for analysis. The mean maximum plasma concentration (C max ) with rectal paracetamol (n = 13) was 6.04 ± 2.21 mg/ml with a T max of 2.5 ± 0.89 h, while with intramuscular paracetamol (n = 16), the C max was 10.34 ± 7.09 mg/ml and the T max 1.47 ± 0.64 h. The area under the concentration-time curve (AUC 0-12 ) was 42.26 ± 22.29 µg.h/ml and 43.60 ± 26.45 µg.hr/ml for rectal and intramuscular paracetamol, respectively. Patients in the intramuscular group needed rescue medication earlier as compared to those in the rectal group (P < 0.05). Conclusion : Although the drug levels achieved with rectal paracetamol were less than that achieved with intramuscular administration, it was higher than the lower limit for analgesic effect (3-5 µg/ml). Patients who received paracetamol intramuscularly needed rescue medication earlier compared to those receiving paracetamol rectally, indicating a more prolonged duration of action with rectally administered paracetamol. Hence, rectal paracetamol can be used as a safe, effective, and more acceptable analgesic alternative in children