Drug development is a tedious and expensive procedure and it takes roughly 10 to 15 years to take a potential treatment from bench to bedside and costs the pharmaceutical companies as much as USD ~2 billion for the process. Delay in investigator-initiated studies can cause financial loss to grant providers (either public or private) and investigator’s reputation may also be at stake. Participant recruitment and retention are two major bottlenecks in conducting clinical trials and contribute vastly to the delays. They are essential for both scientific validity of the clinical study and economic reasons. Thus, issues in recruitment and retention should be addressed and minimized. A proper recruitment and retention plan incorporating adequate communication between all stakeholders will eventually avoid the delays in drug development and make treatments available to the consumer at an earlier date and at a more affordable price. Awareness of challenges and reviewing strategies that can optimise recruitment and retention will facilitate drug development. The article gives a first-person perspective on challenges and proposed solutions from an experienced clinical study centre in a tertiary care hospital.

Is based on observations in practice or in response to their patient's needs. These are called as “Investigator- initiated studies” and these may not have the funding support of the pharmaceutical industry. Hence, the investigator must make sure that he/she complies with the country's regulatory requirements. In the past decade, several changes have dotted the regulatory landscape in the country and have changed the way in which academic research is carried out. The present article outlines regulatory requirements for academic research giving their historical evolution, the key bodies in India that govern or oversee research, along with “must know” and “good to know” facets for the conduct of clinical research in the country....

Background. Liraglutide in a 3.0 mg subcutaneous dose daily is approved for weight reduction. Objectives. Objectives are to evaluate the efficacy and safety of liraglutide 3.0 mg in patients with overweight and obesity irrespective of diabetic status. Methods. We conducted an electronic database search in PubMed, Embase, and https://ClinicalTrial.gov to identify all randomized control trials (RCTs) that evaluated the efficacy and safety of liraglutide 3.0 mg dose compared to placebo in overweight (≥27 kg/m²) and obese (≥30 kg/m²) patients above 18 years of age. Results. We compared the pooled estimate of the study results between liraglutide 3.0 mg groups and placebo groups both in diabetic and nondiabetic patients. The efficacy outcomes that were found to be significant among respective studies involving nondiabetic patients vs. diabetic patients were mean change in body weight from baseline: 12 studies [MD = −5.04 kg (95% CI = −5.60, −4.49), P < 0.001, I² = 92.95%] vs. 2 studies [MD = −4.14 kg (95% CI = −4.95, −3.32), P < 0.001, I² = 0%], reduction in waist circumference from baseline: 8 studies [MD = −3.64 cm (95% CI = −4.43, −2.85), P < 0.001, I² = 96.5%] vs. 2 studies [MD = −3.11 cm (95% CI = −3.88, −2.34), P < 0.001, I² = 0%], BMI reduction from baseline: 5 studies [MD = −1.95 kg/m² (95% CI = −2.22, −1.68) vs. 1 study [MD = −1.86 kg/m² (95% CI = −2.14, −1.57), P < 0.001, I² = 0%, P < 0.001, I² = 95.6%], proportion of patients losing more than 5% of weight loss from baseline: 8 studies [RR = 2.21, (95% CI = 1.89, 2.58), P = 0.03, I² = 59.02%] vs. 2 studies [RR = 2.34, (95% CI = 1.93, 2.85), P = 0.39, I² = 0.00%], and 10% weight loss from baseline: 7 studies [RR = 3.36, (95% CI = 1.92, 5.91), P = 0.00, I² = 87.03%] vs. 2 studies [RR = 3.64, (95% CI = 2.46, 5.40), P = 0.81, I² = 0.00%]. Safety outcome assessment with use of liraglutide 3.0 mg compared with placebo in respective nondiabetic vs. diabetic patients revealed significant proportion of patients experiencing the adverse events: 9 studies [RR = 1.11, (95% CI = 1.04, 1.18), P = 0.00 I² = 79.15%] vs. 2 studies [RR = 1.06, (95% CI = 1.01, 1.11), P = 0.42, I² = 0.03%] but similar risk of serious adverse events: 9 studies [RR = 1.03, (95% CI = 0.70, 1.51), P = 0.26, I² = 18.54%] vs. 2 studies [RR = 1.11, (95% CI = 0.67, 1.84), P = 0.25, I² = 23.77%] and TDAEs: 4 studies [RR = 0.89, (95% CI = 0.35, 2.28), P = 0.03, I² = 61.89%] vs. 1 study [RR = 2.53, (95% CI = 1.00, 6.37)]. However, the pooled estimates irrespective of the glycaemic status were mean change in body weight from baseline: 14 RCT [MD = −4.91 kg (95% CI = −5.43, −4.39), P < 0.001, I² = 92.35%], reduction in waist circumference from baseline: 10 studies [MD = −3.55 cm, (95% CI = −4.21, −2.89), P < 0.001, I² = 94.99%], BMI reduction from baseline: 6 studies [MD = −1.86 kg/m², (95% CI = −2.14, −1.57), P < 0.001, I² = 96.14%], and proportion of patients losing more than 5% and 10% of weight from baseline: [RR = 2.23, (95% CI = 1.98, 2.52), P < 0.001, I² = 48.87%] and [RR = 3.28, (95% CI = 2.23, 4.83), P < 0.001, I² = 78.98%], respectively. Also, the proportion of patients experiencing the adverse event was more with liraglutide 3.0 mg compared with placebo 11 study [RR = 1.09, (95% CI = 1.04, 1.15), P < 0.01, I² = 76.60%] and similar risk for both serious adverse events: 11 studies [RR = 1.09, (95% CI = 1.04, 1.15), P < 0.01, I² = 76.60%] and TDAEs: 5 studies [RR = 1.14, (95% CI = 0.50, 2.60), P < 0.01, I² = 64.93%] with liraglutide compared with placebo. Conclusions. Liraglutide in 3.0 mg subcutaneous dose demonstrated significant weight reduction with a reasonable safety profile for patients with overweight or obesity regardless of diabetic status compared to placebo.

Urinary tract infections (UTI) are among the most frequent medical conditions requiring outpatient treatment. Single dose oral fosfomycin (300 mg) and the older nitrofurantoin (100 mg for 5 days) have been found to be more effective than other first-line drugs in multiple studies. This systematic review and meta-analysis were carried out with the objective of evaluating their comparative efficacy and safety in the management of uncomplicated UTI. Two authors independently searched PubMed, Cochrane Central, Embase, and Google Scholar till Nov 2020 using MeSH terms and free text. Randomized controlled trials (RCTs) comparing both drugs for efficacy and safety in uncomplicated UTI in adult women were included. The primary outcome measures were microbiological and clinical cure rates. The search resulted in n = 663 studies out of which only four studies (three for treatment of uncomplicated UTI in women and one for asymptomatic bacteriuria in pregnancy) satisfied the selection criteria. No significant differences in clinical, (RR 0.95, 95% CI – 0.81, 1.12) and microbiological cure, (RR 0.96, 95% CI – 0.84, 1.08) were found within 4 weeks of treatment. The incidence of adverse events was found to be more in fosfomycin relative to the nitrofurantoin group (RR 1.05, 95% CI – 0.59, 1.87). Hence, single-dose fosfomycin presents a potentially useful and safe treatment option for the treatment of uncomplicated UTI in women and asymptomatic bacteriuria in pregnancy.

Poststroke cognitive impairment (PSCI) refers to any level of cognitive decline occurring after a stroke, ranging from mild to severe impairments, while PSCI with dementia describes a more severe form where the cognitive decline significantly affects daily functioning and meets the clinical criteria for dementia. PSCI occurs in more than half of individuals who have had a stroke. Despite its high prevalence, the pharmacotherapeutic options for PSCI are limited. Several pharmacotherapeutic options like cholinesterase inhibitors (e.g., donepezil, galantamine, and rivastigmine) and N ‐methyl‐ d ‐aspartate receptor antagonists (e.g., memantine) have shown potential in improving cognitive functions. However, their overall effectiveness remains inconsistent across different studies and patient populations. Newer drugs such as citicoline, cilostazol, and antidepressants have shown promise, but further research is needed to validate their efficacy and safety specifically for PSCI management.

Introduction: Tirzepatide, a dual glucose‐dependent insulinotropic peptide (GIP) and glucagon‐like Peptide 1 (GLP‐1) analogue, is a novel medication with comparable pharmacological characteristics and has demonstrated promising weight reduction outcomes in its antidiabetic trials following the approval of liraglutide and semaglutide for long‐term weight control. Nonetheless, this efficacy has not been fully explored, so this meta‐analysis was aimed to measure the weight loss efficacy and safety of tirzepatide in adults with overweight or obesity. Methods: We searched the PubMed, Cochrane, and Embase databases for RCTs of once‐weekly tirzepatide vs. placebo or GLP‐1 receptor agonists. We included studies involving adult participants who were overweight or obese despite T2DM or OHA use, with a trial duration of at least 20 weeks. The primary outcomes accounted for the mean difference in weight from baseline in the three doses of tirzepatide compared to placebo and GLP‐1 receptor agonists, separately. The secondary outcomes included safety profiles and achievement of categorical weight loss of 5%, 10% and 15%. We performed the statistical analysis on RevMan 5.4, GRADE assessment using GRADEpro GDT and the quality of the included studies assessed using the Cochrane risk‐of‐bias (Version 2) tool. Results: We identified six RCTs in which the data of 6266 subjects were analysed. Once‐weekly doses (5, 10 and 15 mg) of tirzepatide were more effective than placebo and GLP‐1 RAs. Also, the proportion of patients achieving categorical weight loss goals was higher in the tirzepatide groups than in others. GRADE assessment also indicated high‐certainty evidence for ≥ 15% weight loss with tirzepatide and moderate‐to‐low certainty for lower thresholds. Gastrointestinal side effects appeared similar between the three doses of tirzepatide and GLP‐1 RAs, but they were significantly higher than placebo might impact tolerability for certain patients. Conclusion: A dose‐dependent tirzepatide was superior to placebo and GLP‐1 RAs in weight reduction. However, the lean mass reduction and tolerability require further investigation. Trial Registration: ClinicalTrials.gov identifier: NCT04255433