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Byline: Charuta. Godbole, Saket. Thaker, Santosh. Salagre, Vyankatesh. Shivane, Nithya. Gogtay, Urmila. Thatte Human paraoxonase 1 (PON1) enzyme protects against atherosclerosis by preventing low-density lipoprotein from oxidative modification. Upregulation of [...]

Byline: Sandhya. Subash, Nithya. Gogtay, Krishna. Iyer, Prajakta. Gandhe, Ritu. Budania, Urmila. Thatte BACKGROUND: Aldehyde oxidase (AO), a molybdoflavoenzyme, is emerging as a key player in drug discovery and metabolism. [...]

Cannabis is one of the world's oldest cultivated plants and the most commonly used recreational drug worldwide. The plant relevant for medicinal use is Cannabis sativa that has two pharmacologically active ingredients - delta-9-tetrahydrocannabinol that is psychoactive and cannabidiol that does not have psychotropic activity. The policy tapestry of Cannabis has undergone a significant change in the past few decades worldwide. Different countries have diverse policies, ranging from classifying use of Cannabis as illicit, to legalization of its use, both for medicinal and recreational purposes. Cannabis products are approved for use, for instance, in multiple sclerosis and Dravet syndrome (US Food Drug and Administration). Against this backdrop, we find that the knowledge foundations for use of Cannabis in clinical trials in India are still evolving. Conducting ethical research within a clinical trials framework is essential to understand dosing, formulation, shelf life, drug-drug interaction, tolerability, and safety before establishing its utility for various indications. In the absence of guidelines or a regulatory framework for conduct of these studies, the various Institutional Ethics Committees (IECs), which are responsible for reviewing projects related to Cannabis, face unique challenges with respect to the basic requirements. The principal investigators (PIs) are equally strained to find local guidance, recommendations, and literature in support of their application to the respective IEC, thus leading to an impasse and delay in initiating the proposed clinical studies with Cannabis. The present article addresses considerations, questions, and issues that affect the conduct of these clinical studies and recommends mandatory documents and some suggested guidelines for use by both PIs and IECs to take studies with Cannabis forward until such time that an interdisciplinary regulatory framework is firmed up by regulatory authority. [ABSTRACT FROM AUTHOR]

Byline: Monalisa. Dhuya, Murari. Pal, Avijit. Hazra, Suparna. Chatterjee, Nithya. Gogtay OBJECTIVES: Cytochrome P[sub]4502D6 (CYP2D6) enzyme metabolizes a quarter of prescription drugs. Polymorphisms of CYP2D6 gene and resultant phenotypic variations [...]

Background: The 1983 US Orphan Drug Act provided impetus for the development of new therapies for rare diseases. Several studies focused on the number of orphan designations over time. However, very few focused on clinical trials that lead to their approval, particularly for infectious diseases. Materials and Methods: All new drug approvals (orphan and non-orphan) by the US Food and Drug Administration (FDA) from January 2010 to December 31, 2020, were identified and details of approvals were taken from the US-FDA labels and summary reports for each drug. The pivotal trials for each were characterized based on their design. We tested the association of the type of drug approval with respect to the characteristics of trial using Chi-square test and generated crude odds ratios with 95% confidence intervals. Results: From the total 1122 drugs approved, 84 were for infectious diseases, of which 18 were orphan drugs and 66 were nonorphan. A total of 35 pivotal trials supported 18 orphan drug approvals, while 115 pivotal trials supported 66 nonorphan drugs. The median number of participants enrolled/trial for orphan drugs was 89, while for nonorphan drugs, it was 452 (P < 0.0001). Blinding was done for 13/35 (37%) orphan drugs versus 69/115 (60%) nonorphan drugs (P = 0.029); randomization was done for 15/35 (42%) orphan drugs versus 100/115 (87%) nonorphan drugs (P < 0.0001) and 20/35 (57%) of the orphan drugs got approval in phase II versus 8/115 (6%) of nonorphan drugs (P < 0.00001). Conclusion: A significant number of orphan drugs get approval based on early phase, nonrandomized, and unblinded with a smaller sample size as compared to nonorphan drugs. [ABSTRACT FROM AUTHOR]

Introduction: The institutional ethics committees (IECs) raise queries following protocol reviews. The quality of these queries would be a useful metric to assess how well the IEC executes its fundamental role of protecting participants. Methods: Queries received after the initial review and replies sent by a single research department were evaluated. A content analysis was done to identify the domains and categories of queries. We categorized these queries as administrative, ethics related, and scientific. The impact of each query in improving the science or safeguarding the rights and safety of research participants (ethics) was evaluated by two authors of this manuscript: one affiliated and the other nonaffiliated to the institute. Kappa statistics were used to evaluate for agreement between the two. Results: A total of 13 studies (investigator-initiated studies [IISs]: 7 and pharmaceutical industry-sponsored studies [PSSs]: 6) formed the final sample size for analysis. The total number of queries was 364 (IIS: 106 and PSS: 258; P < 0.001). With regard to the categories, we found n = 42 (11.54%) to be irrelevant at that stage of the review process; n = 51 (14.01%) were about information already available which the IEC had missed; n = 67 (18.41%) queries where the IEC needed paraphrasing; n = 50 (13.74%) were entirely relevant with the need for further clarification; and n = 154 (42.31%) had been missed by the investigator during the initial submission. The overall agreement between the affiliated and unaffiliated investigators was just 12.9% (P < 0.001). Conclusions: We found that approximately 25% of the queries raised by the IEC were redundant. It is our opinion that this redundancy could have been channeled into greater focus on scientific and ethical aspects of the protocol. Ongoing dialog between investigators and ethics committees may help address this. Perspectives between the affiliated and the unaffiliated investigators with regard to the relevance of queries were grossly different. [ABSTRACT FROM AUTHOR]

Byline: Kannan. Sridharan, Chenna. Reddy Sannala, Surulivelrajan. Mallayasamy, Ayyappa. Chaturvedula, Prashant. Kadam, Nivrutti. Hase, Akash. Shukla, Nithya. Gogtay, Urmila. Thatte OBJECTIVES: We attempted to develop a population pharmacokinetic model for [...]

Byline: Nitin. Mali, Siddharth. Deshpande, Niteen. Karnik, Nithya. Gogtay, Renuka. Munshi, Jigeeshu. Divatia, Sanjay. Wagle, Kannan. Sridharan, Urmila. Thatte Rationale: Antibacterials are largely prescribed to the intensive care unit (ICU) [...]