Binny Krishnankutty

Data management in clinical research: An overview

Clinical Data Management (CDM) is a critical phase in clinical research, which leads to generation of high-quality, reliable, and statistically sound data from clinical trials. This helps to produce a drastic reduction in time from drug development to marketing. Team members of CDM are actively involved in all stages of clinical trial right from inception to completion. They should have adequate process knowledge that helps maintain the quality standards of CDM processes. Various procedures in CDM including Case Report Form (CRF) designing, CRF annotation, database designing, data-entry, data validation, discrepancy management, medical coding, data extraction, and database locking are assessed for quality at regular intervals during a trial. In the present scenario, there is an increased demand to improve the CDM standards to meet the regulatory requirements and stay ahead of the competition by means of faster commercialization of product. With the implementation of regulatory compliant data management tools, CDM team can meet these demands. Additionally, it is becoming mandatory for companies to submit the data electronically. CDM professionals should meet appropriate expectations and set standards for data quality and also have a drive to adapt to the rapidly changing technology. This article highlights the processes involved and provides the reader an overview of the tools and standards adopted as well as the roles and responsibilities in CDM.

Comparative evaluation of four therapeutic regimes in chikungunya arthritis: a prospective randomized parallel-group study

Abstract Objective To evolve a treatment protocol for patients presenting in acute stage of chikungunya by identifying the best regimen from four treatment regimes. Materials and methods One hundred and twenty patients diagnosed to have chikungunya arthritis clinically were randomized to one of four groups receiving combinations of aceclofenac (200 mg/day), hydroxychloroquine (400 mg/day) and prednisolone (10 mg/day). Group A received aceclofenac alone; Group B received aceclofenac plus hydroxychloroquine; Group C received aceclofenac and prednisolone and Group D, all three agents. Study medications were given for 6 weeks with weekly follow-ups followed by a 6 weeks drug-free follow-up with visits at week 8 and week 12. Efficacy variables including visual analog scale (VAS) for pain, 20-point modified Barthel index for activities of daily living (ADL) and instrumental activities of daily living (IADL) were assessed and recorded during start of therapy and at all follow-up visits. Results Significant (P Conclusion Addition of prednisolone, and not hydroxychloroquine, to aceclofenac reduced pain and improved the quality of life in patients with acute chikungunya arthritis, compared to aceclofenac given alone in the management of early chikungunya fever. We propose a combination of non-steroidal anti-inflammatory drugs with corticosteroid as the best regimen in treating acute chikungunya cases with arthralgia.

Basics of case report form designing in clinical research.

Case report form (CRF) is a specialized document in clinical research. It should be study protocol driven, robust in content and have material to collect the study specific data. Though paper CRFs are still used largely, use of electronic CRFs (eCRFS) are gaining popularity due to the advantages they offer such as improved data quality, online discrepancy management and faster database lock etc. Main objectives behind CRF development are preserving and maintaining quality and integrity of data. CRF design should be standardized to address the needs of all users such as investigator, site coordinator, study monitor, data entry personnel, medical coder and statistician. Data should be organized in a format that facilitates and simplifies data analysis. Collection of large amount of data will result in wasted resources in collecting and processing it and in many circumstances, will not be utilized for analysis. Apart from that, standard guidelines should be followed while designing the CRF. CRF completion manual should be provided to the site personnel to promote accurate data entry by them. These measures will result in reduced query generations and improved data integrity. It is recommended to establish and maintain a library of templates of standard CRF modules as they are time saving and cost-effective. This article is an attempt to describe the methods of CRF designing in clinical research and discusses the challenges encountered in this process.

Granulocyte colony-stimulating factor (filgrastim) in chemotherapy-induced febrile neutropenia

Background: The use of granulocyte colony-stimulating factors to treat patients with chemotherapy-induced neutropenia is well accepted. To assess whether administration of filgrastim along with standard empiric antibiotic therapy is beneficial for patients with chemotherapy-induced febrile neutropenia (FN), we conducted an open, non-randomized clinical trial. Materials and Methods: This was a prospective, open, Phase IV clinical trial in patients receiving chemotherapy for histologically confirmed cancer, with an oral temperature of >38.2°C and absolute neutrophil count (ANC) of <500/mm 3. Filgrastim was administered subcutaneously in a dose of 5 mcg/kg/day, 24 hours after administration of cytotoxic therapy, for up to two weeks or until the ANC reached 10,000 cells/mm 3. The parameters of assessment included duration of neutropenia, fever, hospitalization and antibiotic usage. Results: All 24 evaluable patients recovered from neutropenia, fever and FN in a median duration of two days. This result is similar to that reported in earlier studies with filgrastim. Despite the acceleration in recovery from neutropenia and fever, it also reduced the duration of hospital stay and usage of intravenous (IV) antibiotic. Only two adverse events were reported, which were of mild nature. Conclusion: Filgrastim, when used in patients with chemotherapy-induced neutropenia, exhibited efficacy in accelerating the recovery from neutropenia and fever comparable to that reported with filgrastim in literature. The data from this study suggest that filgrastim is effective in the treatment of chemotherapy-induced neutropenia and is well tolerated by Indian patients.

Efficacy and safety of topical halometasone in eczematous dermatoses in Indian population: An open label, noncomparative study

Background: Topical steroids remain the mainstay of treatment in eczema, an inflammatory skin reaction characterized by pruritus, redness, scaling, and clustered oozing papulovesicles. Halometasone is a new potent corticosteroid approved in the Indian market for topical application in the treatment of dermatitis. Aims: To evaluate the efficacy and safety of halometasone in the treatment of acute or chronic noninfected eczematous dermatosis in Indian population. Materials and Methods: A prospective, open, multicentric, phase 3, noncomparative clinical trial conducted at outpatient departments of seven centres. Two hundred endogenous eczema patients meeting study criteria were enrolled. Halometasone 0.05% cream was applied twice daily for 30 days in chronic and 20 days in acute eczema patients. Calculation of eczema area and severity index, and assessment of investigators global assessment of severity of eczema and severity of pruritus score were done at each visit and compared with baseline. All adverse events (AE) were captured and documented. Laboratory investigations including haematological tests, urinalysis, renal and liver function tests were performed at baseline and at end of treatment. Results: Of the 200 patients enrolled, 180 were chronic and 20 were acute eczema patients. It was found that there was a significant (P<0.001) improvement in all efficacy parameters compared with baseline. The treatment was shown to be successful in 91% patients. AE were reported in 30 patients and there was no serious AE reported. There was no clinically significant difference in laboratory investigations with treatment. Conclusions: Halometasone was shown to be safe and very effective in Indian patients with acute and chronic eczema and the drug was well tolerated.

Preclinical pharmacological profile of Eberconazole: A review and update

Eberconazole is a broad-spectrum imidazole antifungal agent used as a topical preparation in the management of cutaneous mycoses. In vitro studies have shown that eberconazole is effective against dermatophytes, candidiasis, yeasts (including those which are triazole resistant) and Pityriasis versicolor. It inhibits fungal lanosterol 14α-demethylase, thereby inhibiting ergosterol synthesis leading to inhibition of fungal growth. In addition to its antifungal activity, it is also effective against Gram-positive bacteria, a property that is useful clinically. It also possesses anti-inflammatory property thus making it a suitable agent in the clinical management of inflamed cutaneous mycoses. Topical application of eberconazole was well tolerated in preclinical studies without any report of delayed hypersensitivity or photosensitivity reactions. There were no phototoxic effects. There was no significant systemic absorption. Animal toxicity studies have shown that it is safe, and the No Observed Effect Level was 2 ml/kg body weight in tested animals. It was not mutagenic and shared similar cytotoxicity profile with other imidazole antifungal products studied. Penetration studies using synthetic membranes revealed that eberconazole intrasets showed less variation as compared to clotrimazole and terbinafine intrasets. Overall amount of eberconazole released was more compared to comparators. In vitro and preclinical studies have demonstrated better therapeutic efficacy with eberconazole than clotrimazole and ketoconazole.