Thursday, 6 December 2012

Pre-clinical and clinical research: Part of drug development process

Preclinical development
Pharmaceutical research plays an essential role in the development of new drug molecules for safe and effective use in patients. Pre-clinical and clinical research is two important phases in drug discovery and development process. It takes about 12 to 16 years to bring a molecule from laboratory to clinical practice. Based on the type of drug molecule, the duration of pre-clinical research varies from 2 to 6 years while clinical research takes approximately 7 to 12 years. Today the challenge with pharmaceutical research is to reduce the lead time of pre-clinical and clinical phases, which can be made possible by adopting newer technologies, using rational drug design process in place of traditional processes.

Pre-clinical research is combination of in vitro, in vivo and ex vivo experiments before the clinical trials. Target identification, target validation, lead identification, lead optimization and finally synthesis of the new drug molecule for a specific disease are important steps of pre-clinical research. After the synthesis of a drug molecule, different tests and experiments are done in laboratory and animal models for the collection of safety and efficacy information for the clinical trials. The primary objective of pre-clinical research is identification of physiological, toxicological and efficacious potential of drug molecule. Study of pharmacodynamics, pharmacokinetics, immunogenicity, immunotoxicity, developmental toxicity, genotoxicity studies and carcinogenicity properties with identification of initial safe dose, target organs and other safety parameters constitute secondary objectives. Regulatory authorities wants to minimise the use of animals in pre-clinical trials due to animal rights issues, so

selection of animals for the pre-clinical trials is another important aspect, normally one rodent and one non-rodent species are used for the same. High quality safety and efficacy data is required by the regulatory authorities before giving approval for conduct of clinical trials in humans in the form of IND (New Drug Application) submission.

Phases of Clinical development
Clinical research determines the safety and efficacy of medications, devices, diagnostic products and treatment regimens discovered for the human use in terms of prevention, treatment, diagnosis or for relieving symptoms of a disease. Successfulness of the pre-clinical research and approval from the regulatory authority are the mandatory requirements for the clinical trials. Clinical trials are divided in 4 phases from phase 1 to 4

Phase 1 clinical trials commonly known as human or clinical Pharmacology trials, first phase of clinical trials conducted in small group of healthy human volunteers (20-100). In this phase the medicinal product is administered first time in human body for identifying pharmacokinetic (absorption, distribution, metabolism, excretion and liberation) properties of drug. The main objective of phase 1 clinical trial is to assess the safety data and safe-dosing range of a drug.

Phase 2 clinical trials commonly known as therapeutic exploratory trials, performed on larger groups (100-300) after the establishment of initial safety of the study drug in Phase 1 clinical trials. The main objective of this phase is to collect the data for effectiveness and safety assessments in patients. Sometimes phase 2 trials are divided into: phase 2a trials and phase 2b trials. Phase 2a trials, commonly known as pilot trials, collect information about pharmacodynamic (dose-response, type of patient, frequency of dosing and find any other issues related to safety and efficacy) properties of drug in patients. Phase 2b trials commonly known as pivotal trials are well-controlled trials to evaluate safety and efficacy in large number of diseased subjects (500-1000), represent the most rigorous demonstration of efficacy.

Phase 3 clinical trials commonly known as therapeutic confirmatory trials usually involves 1,000 to 5,000 patients in multicentric setups. The main objective of this phase is to confirm safety, efficacy and identify adverse events related to drug molecule. Sometimes phase 3 trials are divided in 2 groups: Phase 3a trials and Phase 3b trials. Phase 3a trials are conducted before the new drug application (NDA) submission to the regulatory to generate additional data on safety and efficacy in relatively large numbers of patients in both controlled and uncontrolled trials. Phase 3b trials sometimes called as peri-approval trials are conducted after NDA submission to the regulatory but before the approval of marketing of the drug. Phase 3b trials may supplement earlier trials, complete earlier trials, or may be directed toward new types of trials (e.g. quality of life, marketing) or Phase IV evaluations.

Phase 4 trials commonly known as post-marketing surveillance, takes place after obtaining marketing approval for the drug. Phase IV trials involves the pharmacovigilance and technical support for the patients and medical professionals. The main objective of these trials is to set up, evaluate and collect long-term safety data for the drug in the form of PSUR (periodic safety update report) as a requirement of regulatory authorities.

Apart from these main 4 phases of clinical trials, 2 other phases of clinical trials - phase 0 and phase 5 - have been recently introduced in the field of clinical research, based on type of the drug or molecule. Phase 0 clinical trials are commonly known as micro-dosing trials, a very small dose of investigational drug is given to the healthy voluntears for the study of efficacy, toxicity and pharmacokinetic properties. Phase 5 clinical trials are also a type of post-marketing surveillance to study the comparative effectiveness research in a specific community or populations.

We at worksure provide all the solutions for the pre-clinical and clinical research, in terms of trial related document (Protocol, CRF, Investigator brochure, ICF & other)preparation, editing & review of sponsor prepared documents, investigator meetings & study result meetings arrangements, SOP preparation, developing QA/QC plan, clinical study reports prepration, abstracts and publication writing, poster/PPTs prepration for conferences and meta-analysis/systematic review prepration. We also provide regulatory solutions and clinical data management services for the clinical trials.


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