Introduction
Aims of pre-clinical studies
Main stages in clinical drug development and challenges from Phase I to Phase IV
Conclusion
- Minimum required contents of a clinical trial protocol.
Introduction
This document contains information related to aims of pre-clinical studies. A brief outline of the main stages in clinical drug development and challenges emerging from it will also be addressed. This would be done by highlighting developments occurring from phases I through IV. An exploration into the minimum required contents of a clinical trial protocol will also be embraced.
Aims of pre-clinical studies
Pre-clinical trials begin before the actual research. According to Talbot and Walker’s (2004) account of Stephens’ Detection of New Adverse Drug Reactions due to these major drug interactions and reactions it is imperative that the product, which is to be used in the accrual trial be safe for subjects to take as a medication. Drugs for example, must be tested to determine pharmacodynamics (PD) how the body responds to the chemicals contains in the medication (Talbot & Walker, 2008)
Main stages in clinical drug development and challenges from Phase I to Phase IV
Clinical trials are placed into stages namely Phase 1, Phase 2, Phase 3 and Phase 4. This largely depends on then life position of the new treatment when the trial begins.
Phase 1 (Phase I)
Phase 1 consist of the initial trials and can be considered to the early stages in the new drug treatment life. Importantly, these are small trials. Subject range from 25-30 patients, who are health and disease free adults or children whose parents have consented to their participation (Di Giovanna & Hayes, 2001).
.Aims/Objectives
These trials are conducted for obtaining data pertaining to a safe dosage as well as dose range for which the drug can be prescribed. It also detects actual and potential side effects of the medication. Excretion of the medication from the body is also evaluated as the pharmacokinetics of the drug is explored. This is the reason for using healthy volunteers because they will eventually be given larger doses of the rial medication to see how well they accommodate its dosage. As such, these subjects as in any other trial are assessed frequently and irregularities documented as evidence of side effects of the drug being administered at various dosages (Di Giovanna & Hayes, 2001).
.Concluding phase 1
Since Phase 1 trials primarily assess doses and side effects. It forms the foundation of the entire trial. This phase of the trial is very significant since it details the first step in finding new treatment interventions, which can be used in many disease conditions as a breakthrough therapy. After all of the Phase 1 study results have been analyzed and validated then researchers could proceed with Phase 2 of the study (Di Giovanna & Hayes, 2001).
Challenge
- Volunteers may put up reaction to drug.
Phase 2 (Phase II)
At least 70% of every 100 trial subjects tested with the new treatment in the Phase 1 level become eligible for moving forward into a Phase 2 trial. Precisely, these studies are very much larger studies are larger than Phase 1 studies because obtaining more safety data becomes extremely necessary. During this phase more precise responses to the drug are observed as well as clarification regarding data collected previously in phase 1. This relates specifically to dose range as well as district prescription doses at it maximum must be thoroughly evaluated (Di Giovanna & Hayes, 2001).
. Aims/Objectives
Phase 2 trials are conducted for obtaining data pertaining to whether the safe dosage as well as dose range for which the drug can be prescribed is effective towards bringing any resolution to the targeted disease. More in-depth evaluations of adverse effects are conducted. This step goes further into exploring how the most effective management of adverse effects as well as the dosage tolerance range to use from the range of doses discovered in the Phase I studies (Di Giovanna & Hayes, 2001).
Concluding phase 1
In the final assessment stages of Phase 2 trials researchers will identify whether the new novel drug is effective or, more importantly, better than the one being used for the disease at the time. If it proves effective or better the drug is then be moved into an expanded Phase 3 study
(Di Giovanna & Hayes, 2001).
Challenge
- During the trial many subject may become unsuitable to continue which alters the sample size.
Phase 3 (Phase III)
Phase 3 trials encompass quite a larger and wider sample of the population than Phases 1 or 2 of the trials. Thousands of subjects are recruited from all over the country and on many occasions across the world (Di Giovanna & Hayes, 2001).
Aims/objectives
The purpose of Phase 3 trials is for comparing the new drug treatment intervention with the most effective existing ones being used at the time known as the standard treatment. Various doses and methods of administering the standard medication are evaluated. Ultimately, the treatment schedule of the drug used in the trial is aligned to the standard drug procedure/dosage of administration during the comparative evaluation (Di Giovanna & Hayes, 2001).
Challenge
- Volunteers may not wish to continue the trial
Phase 4 (Phase IV)
Phase 4 trials are conducted after the trial drug has proven its effectiveness and received a product license by the MHRA. Primarily these trials compare available drug treatments for the particular disease drugs that are eligible to be prescribed by doctors and not those which are still going through trials (Di Giovanna & Hayes, 2001).
Aims/objectives
This phase is often undertaken by pharmaceutical companies because they want to further investigate phases 1, 2 and 3 particularly the side effects safety drug doses as well as the long term risks and benefits. Insidiously researchers evaluate the effectiveness of the drug from a broader perspective since the sample is much larger and more representative of the population
Challenges
- Subjects do not follow through with treatment guidelines
- Participating agencies are non-compliant with common reference document of the protocol.
Conclusion
Minimum required contents of a clinical trial protocol embody a rationale, which is scientific in nature; clearly stated objective; research design, methodology, statistical considerations as the organization responsible for conducting the trial (Cox Gad, 2009).
Further, According to Di Giovanna and Hayes (2001) there are 14 Good Clinical Practice (GCP) guidelines. They include:-
- ‘The rights, safety and well-being of the trial subjects shall prevail over the interests of science and society’ (Di Giovanna & Hayes, 2001 p 181).
- ‘A trial shall be initiated only if an ethics committee and the licensing authority comes to the conclusion that the anticipated therapeutic and public health benefits justify the risks and may be continued only if compliance with this requirement is permanently monitored policy’ (Di Giovanna & Hayes, 2001 p 181).
- ‘Clinical trials shall be conducted in accordance with the principles of the Declaration of Helsinki’ (Di Giovanna & Hayes, 2001 p 181).
- ‘The protocol shall provide for the definition of inclusion and exclusion of subjects participating in a clinical trial, monitoring and publication policy’ (Di Giovanna & Hayes, 2001 p 181).
References
Cox Gad, S (2009). Clinical Trials Handbook. John Wiley and Sons
Di Giovanna, I., & Hayes, G.(Eds) (2001) Principles of Clinical Research. Petersfield,
Wrightson Biomedical Publishing.
Cox Gad, S (2009). Clinical Trials Handbook. John Wiley and Sons
Talbot, J., &Waller, P. (2004) Stephens’ Detection of New Adverse Drug Reactions, 5th
edition. Chichester, J.Wiley & Sons Ltd.
