Clinical trials are emerging as an important activity in India as it is an essential component of the drug discovery and development program to which India is committed. The only robust way to evaluate a new medicine is by doing properly designed clinical trials. In addition to advancing science, clinical trials offer myriad benefits to the participants. The recent hue that created in India about clinical trials is probably an exaggeration of facts. However, these points to the need for ensuring proper compliance with the regulatory norms and proper training of concerned personnel in good clinical practice (GCP). This will ensure that India continues to reap the benefits of clinical trials and also become a world leader in this field.

Institutional Review Boards (IRBs) are an important link in subject protection program, and their function defines ethical credentials of research. Of late there has been a furore in the country over the number of deaths in clinical research, and allegations of unethical research. Clinical trials have been discussed in medical and lay press and even in the parliament, these discussions called for strengthening the subject protection program. The Central Drug Standards and Control Organization (CDSCO), amended the Schedule Y, by issuing three amendments to introduce new compensation rules and registration of IRBs functioning in the country. IRBs in India face a variety of challenges, and need support from the regulators or independent experts. This is also an opportunity to revamp the subject protection program and strengthen the IRB functioning. An independent advisory body comprising of experts who have hands on experience in administering IRBs, is essential to provide support to IRBs in the country. This body should be independent of regulatory influence and work with IRBs to strengthen them.

Ethics committee (EC) organization and standardization is an important aspect of clinical research. There is a healthy trend worldwide to register and/or accredit research ECs reviewing clinical research. This article tries to focus on the existing model of ECs worldwide, as against the Indian backdrop. The article reviews literature, journals, websites, and studies conducted in 10 different countries and outlines the working model of ECs in these countries. The challenges faced during the ethical review, especially in case of multicenter trials, have been identified. A solution has been suggested to overcome these challenges, and to ensure the overall smooth functioning of clinical trials. The article proposes the development of national and regional central ECs to counter the current drawbacks in the ethical review mechanisms in India.

Objective: To evaluate the effects of botropase on various clotting factors in human volunteers. Materials and Methods: It was a prospective open label study conducted on human healthy volunteers. After the baseline screening, subjects fulfilling inclusion criteria were enrolled. On the study day, 1 ml of botropase was administered intravenously and after an hour same dose of botropase (1 ml) was given by intramuscular (IM) route. The efficacy and safety parameters were monitored up to 72 h from the time of intravenous (IV) administration. Results: A total of 15 volunteers, belonging to 24-35 years of age were included in the study. Botropase significantly reduced the plasma level of fibrinogen and fibrin degradation products after 5 min of IV administration (P < 0.05). In addition, factor X was observed to reduce constantly by botropase administration suggesting enhanced turnover between 5 and 20 min of IV administration. Although botropase reduced clotting and bleeding time in all the volunteers, the data remains to be statistically insignificant. Conclusion: Present study demonstrated the safety and efficacy of botropase in human healthy volunteers. The study has shown that it is a factor X activator and reduces effectively clotting and bleeding time.

Background: Recent research using serum high sensitivity C-reactive protein (hs-CRP) has evidenced existence of low grade systemic inflammation in asthmatics whose correlation with various clinical indices is not fully studied. Objective: To investigate the relationship between systemic inflammation and various clinical and treatment characteristics of asthma. Materials and Methods: Forty asthmatics (22 steroid inhaling and 18 steroid naïve) and 40 healthy subjects matched for age and sex were examined cross-sectionally. Along with clinical assessment, serum hs-CRP levels were measured for all subjects using latex enhanced immunoturbidometry method. Results: Serum hs CRP levels were significantly higher in steroid naïve asthmatics when compared to normal subjects (0.93 ± 1.18 vs 0.24 ± 0.31 mg/dL, respectively; Mann-Whitney U test, P < 0.001). This association persisted after adjusting for age, gender, body mass index (BMI), and socioeconomic status (adjusted odds ratio 10.47; 95% CI 1.88-58.3; P < 0.01). Steroid inhaling asthmatics had serum hs-CRP levels comparable with control group (0.17 ± 0.18 vs 0.24 ± 0.31 mg/dL respectively, P > 0.05). Among the clinical and treatment related variables, duration of inhaled steroids usage alone correlated significantly with serum hs-CRP levels (Pearson correlation coefficient r = 0.449, P < 0.05), which was independent of age, BMI, duration of illness, and frequency of emergency visits. Conclusion: This study confirms the existence of low grade systemic inflammation in asthma which is effectively controlled by inhaled steroids. Such an effect of inhaled steroids appears to be more pronounced in recent users than that of long-term users, possibly due to lower adherence rate among the latter.

Aim and Objectives: The present study was undertaken in 20 healthy human volunteers to evaluate the effect of a herbal bioenhancer, Carum carvi on pharmacokinetics of rifampicin, isoniazid, and pyrazinamide in fixed dose combination (FDC). Materials and Methods: It was a prospective, two-period, open-label, cross-over experiment on 20 healthy human male volunteers. The volunteers were administered a single dose of FDC containing rifampicin (450 mg), isoniazid (300 mg), and pyrazinamide (1000 mg) and after 10 days washout period the same FDC along with C. carvi extract (100 mg) was administered. Blood samples were collected at different time-points and analyzed by high-performance liquid chromatography (HPLC). Detailed pharmacokinetic parameters were calculated, which included C_max , area under curve (AUC), time to reach maximum plasma concentration (T_max ), clearance (Cl), volume of distribution (V_d ), and half-life (t _½ ). Results: Additions of C. carvi extract lead to increase in plasma levels of rifampicin, isoniazid, and pyrazinamide. The bioavailability indices C_max of rifampicin increased from 4.57 ± 0.19 to 5.95 ± 0.19 (P = 0.000) and AUC increased from 40.11 ± 1.69 to 53.01 ± 1.88 (P = 0.000). Similarly, C_max of isoniazid increased from 2.66 ± 0.16 to 3.62 ± 0.16 (P = 0.000) and AUC from 17.72 ± 0.78 to 22.87 ± 0.94 (P = 0.000). The bioavailability indices of pyrazinamide also revealed an increase in C_max from 18.81 ± 0.79 to 25.06 ± 1.14 (P = 0.000) and AUC from 107.65 ± 4.42 to 137.71 ± 5.92 (P = 0.000), respectively. Conclusion: C. carvi acts as a bioenhancer and modifies the kinetics of antitubercular treatment (ATT) favorably.

Background: Intravenous patient-controlled analgesia (PCA) with morphine is commonly used for post-operative pain after major surgery. Ketamine has analgesic property at lower doses, and in combination with opioids it could have synergistic effect. The aim of this study is to determine effects of the addition of ketamine to morphine for PCA after orthopedic surgery. Materials and Methods: In this double-blind randomized clinical trial, 60 patients were randomly allocated to receive PCA consisting: Group 1 (morphine 0.2 mg/ml), Group 2 (morphine 0.2 mg/ml + ketamine 1 mg/ml), and Group 3 (morphine 0.1 mg/ml + ketamine 2 mg/ml). In this, anesthesiologists managed study, patients had orthopedic surgery. Assessments were made at 24 h and 48 h post-operatively. Visual analog scale (VAS) was used for recording pain score. PCA morphine use was recorded at 24 h and 48 h. VAS scores over 48 h were analyzed with analysis of variance for repeated measures. Significance level was taken as 0.05. Results: There is no significant difference between demographic information of the three groups ( P > 0.05). Control of pain in Group 2 and Group 3 was better than in Group 1 (only morphine) ( P = 0.001) but there was no significant difference between Group 2 and Group 3 ( P > 0.05). Rate of narcotic consumption in groups 2 and 3 was significantly lower than Group 1 ( P < 0.05). Conclusion: After orthopedic surgery, the addition of ketamine to morphine for intravenous PCA was superior to Intravenous PCA opioid alone. The combination induces a significant reduction in pain score and cumulative morphine consumption.

Urticaria is a heterogeneous group of diseases. Chronic urticaria significantly impacts quality-of-life of patients. Second generation, non-sedating antihistamines are recommended as first line treatment for chronic spontaneous urticaria. In patients with inadequate control of symptoms, increase in dosage of non-sedating antihistamines up to four fold has been recommended. This recommendation is based on low cost, good safety and good evidence of efficacy of non-sedating, second generation antihistamines. This article reviewed Indian data on up-dosing of antihistamines in chronic urticaria. There is a need for well-designed clinical trials with ­up-dosing of individual antihistamines in Indian patients.