Investigators' viewpoint of clinical trials in India: Past, present and future

India's success in producing food and milk for its population (Green Revolution and White Revolution) happened because of scientific research and field trials. Likewise improving the health of Indians needs clinical research and clinical trials. A Large proportion of the sick Indians are poor, illiterate with no access to good health care. They are highly vulnerable to inducement and exploitation in clinical trials. The past two decades saw the rise and fall of clinical trials in India. The rise happened when our regulators created a favorable environment, and Indian investigators were invited to participate in global clinical trials. The gap between the demand and supply resulted in inadequate protection of the trial participants. Reports of abuses of the vulnerable trial participants followed by public interest litigations led to strengthening of regulations by the regulators. The stringent new regulations made the conduct of clinical trials more laborious and increased the cost of clinical trials in India. There was a loss of interest in sponsored clinical trials resulting in the fall in global clinical trials in India. Following repeated appeals by the investigators, the Indian regulators have recently relaxed some of the stringent regulations, while continuing to ensure the adequate patient protection. Clinical trials that are relevant to our population and conducted by well-trained investigators and monitored by trained and registered Ethics Committees will increase in the future. We must remain vigilant, avoid previous mistakes, and strive hard to protect the trial participants in the future trials

Pharmacovigilance Symposium ISCR Annual Conference Jan 5, 2013: Safety aspects of hard endpoint or outcome trials

The articles describes some highlights of the Pharmacovigilance Symposium held during Annual conference

Cancer mortality in India: a nationally representative survey.

BACKGROUND: The age-specific mortality rates and total deaths from specific cancers have not been documented for the various regions and subpopulations of India. We therefore assessed the cause of death in 2001-03 in homes in small areas that were chosen to be representative of all the parts of India. METHODS: At least 130 trained physicians independently assigned causes to 122,429 deaths, which occurred in 1·1 million homes in 6671 small areas that were randomly selected to be representative of all of India, based on a structured non-medical surveyor's field report. FINDINGS: 7137 of 122,429 study deaths were due to cancer, corresponding to 556,400 national cancer deaths in India in 2010. 395,400 (71%) cancer deaths occurred in people aged 30-69 years (200,100 men and 195,300 women). At 30-69 years, the three most common fatal cancers were oral (including lip and pharynx, 45,800 [22·9%]), stomach (25,200 [12·6%]), and lung (including trachea and larynx, 22,900 [11·4%]) in men, and cervical (33,400 [17·1%]), stomach (27,500 [14·1%]), and breast (19,900 [10·2%]) in women. Tobacco-related cancers represented 42·0% (84,000) of male and 18·3% (35,700) of female cancer deaths and there were twice as many deaths from oral cancers as lung cancers. Age-standardised cancer mortality rates per 100,000 were similar in rural (men 95·6 [99% CI 89·6-101·7] and women 96·6 [90·7-102·6]) and urban areas (men 102·4 [92·7-112·1] and women 91·2 [81·9-100·5]), but varied greatly between the states, and were two times higher in the least educated than in the most educated adults (men, illiterate 106·6 [97·4-115·7] vs most educated 45·7 [37·8-53·6]; women, illiterate 106·7 [99·9-113·6] vs most educated 43·4 [30·7-56·1]). Cervical cancer was far less common in Muslim than in Hindu women (study deaths 24, age-standardised mortality ratio 0·68 [0·64-0·71] vs 340, 1·06 [1·05-1·08]). INTERPRETATION: Prevention of tobacco-related and cervical cancers and earlier detection of treatable cancers would reduce cancer deaths in India, particularly in the rural areas that are underserved by cancer services. The substantial variation in cancer rates in India suggests other risk factors or causative agents that remain to be discovered. FUNDING: Bill & Melinda Gates Foundation and US National Institutes of Health

Prevalence estimation of microsatellite instability in colorectal cancers using tissue microarray based methods – A tertiary care center experience

Aim: Microsatellite instability (MSI) pathway is known to be implicated in carcinogenesis of 15% colorectal carcinomas (CRC), including 2%–3% of cases of Lynch syndrome, as per western literature. MSI status has important prognostic and therapeutic implications. The prevalence of MSI in Indian CRC patients is unknown. We aimed to determine the prevalence by studying 231 consecutive unselected cases of CRC. Methods: Tissue microarrays using duplicate cores per case for 141 cases, and whole tissue sections for 90 cases, were used. Immunohistochemistry with four mismatch repair (MMR) markers – MLH1, MSH2, MSH6, and PMS2 was performed. Molecular analysis for MSI status was performed in 18 randomly selected cases. Correlation with various clinical and histopathological features was done using univariate and multivariate analysis. Results: Loss of MMR immunohistochemical (IHC) was seen in 53/231 cases, i.e. 22.94% (95% confidence interval 17.52%–28.36%). MLH1-PMS2 dual loss comprised 13.9%, MSH2-MSH6 7.4%, and isolated PMS2 loss in 1.73% of cases. Univariate analysis showed significant association with age (<60 years), right-sided tumor location, histologic type, high grade, the presence of severe intratumoral lymphocytic (ITL) and peri-tumoral lymphocytic response, and N0 nodal stage. On multivariate analysis, independent variables were age < 60 years, right-sided location, and severe ITL. Molecular testing for MSI corroborated with the IHC results. Conclusion: The study results show a slightly higher prevalence of MSI-H phenotype, compared to Western literature, stressing the need for more widespread testing for better clinical management and identification of possible hereditary colon cancer syndrome

Characteristics and outcomes of gallbladder cancer patients at the Tata Medical Center, Kolkata 2017–2019

Abstract Background The north and north‐eastern regions of India have among the highest incidence of gallbladder cancer (GBC) in the world. We report the clinicopathological charateristics and outcome of GBC patients in India. Methods Electronic medical records of patients diagnosed with GBC at Tata Medical Center, Kolkata between 2017 and 2019 were analyzed. Results There were 698 cases of confirmed GBC with a median age of 58 (IQR: 50–65) years and female:male ratio of 1.96. At presentation, 91% (496/544) had stage III/IV disease and 30% (189/640) had incidental GBC. The 2‐year overall survival (OS) was 100% (95% CI: 100–100); 61% (95% CI: 45–83); 30% (95% CI: 21–43); and 9% (95% CI: 6–13) for stages I–IV, respectively (p = <0.0001).   For all patients, the 2‐year OS in patients who had a radical cholecystectomy followed by adjuvant therapy (N = 36) was 50% (95% CI: 39–64), compared to 29% (95% CI: 22–38) for those who had a simple cholecystectomy and/or chemotherapy (N = 265) and 9% (95% CI: 6–14) in patients who were palliated (N = 107) (p = <0.0001). Conclusion The combined surgical/chemotherapy approach for patients with stage II GBC showed the best outcomes. Early detection of GBC remains problematic with the majority of patients presenting with stage III–IV and who have a median survival of 9.1 months. Our data suggests that the tumor is chemoresponsive and multi‐center collaborative clinical trials to identify alternative therapies are urgently required