Features of clinical trials

the slide is about basic concept of the clinical trials

1. F eatures of clinical trials By Drashti P atel (15mph803) RA & QA, IPNU

2. Contents: What are clinical trials? Who are involved in clinical trials? Why are clinical trials performed ? Phases of clinical trials Elements of clinical trials Informed consent form Institutional Ethical C ommittee Recent scenario C onclusion

3. What are clinical trials? Clinical trials are research studies that explore whether a medical strategy, treatment, or device is safe and effective for humans. The Code of Federal Regulations (CFR) defined it as the clinical investigation of the drug that is administered or dispensed to one or more human subjects These studies also may show which medical approaches work best for certain illness or groups of people. It helps in advancing the patients care.

4. Clinical trial is the main stay for bringing out new drugs to the market. For every 10,000 to 30,000 drug molecule screened, only one reaches to the market. The four possible outcomes of clinical trials are: Positive trial: shows that the new treatment has a large beneficial effect and is superior to standard treatment. Non inferior trial: shows that the new treatment is equivalent to standard treatment.

5. Inconclusive trial: shows that the new treatment is neither clearly superior nor clearly inferior to standard treatment. Negative trial: shows that the new treatment is inferior to standard treatment.

6. Who are involved in clinical trials? Patient / Healthy volunteer Clinical Pharmacologist, Clinical Investigator & team: [Qualified and competent] Institution where trials are held : [ Approval required] Ethical Review Board or Institutional Ethical Committee: Sponsor Regulatory Authorities:

7. Why are clinical trials performed ? To provide evidence that the drug that has been discovered is safe and effective ,and this evidence can be given through clinical trials. Before clinical trials, preclinical trials are done.(i.e. testing on animals before human testing is permitted ) Acute, sub-acute and chronic toxicities are studied in pre-clinical trials.

8. Through preclinical studies we can know the therapeutic action and the pharmacokinetic action. It takes about 2 years on average to get data on Safety, Efficacy, Toxicity, Pharmacokinetics and pharmacodynamics studies. And after this we can file for IND (Investigational new drug) and can now start with clinical trial studies. Clinical trials are organized into different phases of research in order to build up a greater understanding of the new treatment, before it is approved or recommended for routine use.

9. Phases of clinical trials T here are 4 phases of clinical trials PHASE 1 : Objective : To assess a safe and tolerated dose. To detect any predictable toxicity. To assess a safe and tolerated dose, pharmacokinetics is studied. Collect data on : dose response relationship, safe dosage range, side effects Detection of any predictable toxicity

10. Contd ….phase 1 First in a small group of 20 to 25. But before starting with that, an ‘ informed consent ’ is must. Started with a small dose. Slowly increase the dose to find a safe tolerated dose. If safe  in a larger group of up to about 50 – 75. These trials are performed by clinical pharmacologist. Takes 3-6 months(70% success rate).

11. PHASE 2 : The drug or treatment is given to patients to see if it is effective and to further evaluate its safety We test whether the patient has desired therapeutic effects at doses that are tolerated by sick patient. Compares the effectiveness and safety of new drug with the standard existing drug. Early phase: (20-200 patient with relevant disease). Therapeutics benefits and ADR are evaluated. Establish a dose range to be used in late phase. Single blinded(only patient knows) comparision with standard drug.

12. Contd ….Phase 2 Late phase: double blinded. Compared with placebo or standard drug. Outcomes: Assesses efficacy against a defined therapeutic end point. Detailed pharmacokinetics and pharmacodynamic data. Establishes a dose and dosage form for future trials. Takes 6 months to 2 years.(35% success rate)

13. Phase 3 Large scale, Randomised, Controlled trials Target population: 250 – 1000 patients Performed by Clinicians in the hospital Minimises errors of phases I and II Here it is confirmed if the drug works in manner proposed for its ultimate general use. It also looks for further beneficial action. To compare experimental or new therapies with standard therapy or competitive therapies. Very large, expensive studies

14. There is comparision with older therapies The toxicity of drugs etc. are studied Vigilant recording of all data. Statistical evaluation of all clinical data. A ll these details are required by FDA for drug approval With all the information on NDA(New Drug Application), FDA evaluates a drug and takes decision on approval. It takes about 5 years. (25% success)

15. PHASE 4: It is also called as POST MARKETING SURVEILLANCE Studies are done after the drug or treatment has been marketed to gather information on the drug’s effect in various populations. Studies are also done on side effects associated with long term use. Helps to detect the rare ADR drug interaction. new uses of drugs.

16. Phase 4 studies may be require by regulatory authorities or may be undertaken by sponsoring company for competitive or other reasons. Harmful effects discovered by phase 4 trials may result in a drug being no longer sold, or restricted to certain uses. Recent eg. is of cerivastatin (baycol and lipobay) and rofecoxib ( V ioxx)

17. Elements of clinical trials Aim or objective Protocol : study design Ethics committee clearance Regulatory approval whenever required Informed consent Implementation of protocol Collection of data Compilation of data, analysis and interpretation Report writing

18. Informed consent form: Voluntary Explained in simple nontechnical language Translated in the native language of the subject Comprehensive information regarding the trials Benefit of new therapy over existing ones Alternative treatments available All possible adverse reactions Freedom to withdraw from the trial at any time, without giving any reason

19. Institutional Ethical Committe It is the committee that has been formally designated to approve, monitor and review biomedical and behavioural research involving humans. Resposibilities: To protect the dignity, rights & well being of patients / volunteers Ensure a competent review of the protocol Advise on all aspects of welfare & safety Ensure scientific soundness of the proposal

20. Composition of IEC 1. Chairperson 2. 1-2 basic medical scientists. 3. 1-2 clinicians from various Institutes 4. One legal expert or retired judge 5. One social scientist / representative of NGO 6. One philosopher / ethicist / theologian 7. One lay person from the community 8. Member Secretary Individuals from other institutions if required Adequate representation of age, gender, community,

21. Recent scenario In recent years, India has positioned itself as one of the major players in the clinical trials arena. Clinical trials constitutes nearly 70% Research and Development costs. A nd the total time taken for drug development constitutes 7-10 years .

22. According to the latest estimates made by the Tufts C entre for the Study of Drug Development, while total research cost have increased by 7.4% per year, the cost of clinical trials on human being has risen over 12%. Considering the relative cost of R&D in India, several MNC pharmaceutical companies, as well as global CRO are increasingly making India a clinical research and development hub.

23. C onclusions Clinical trials often yield important results that affect health and well being. Must follow guidelines and protocol. Must ensure well being of participants.

24. REFERENCE: https:// en.wikipedia.org/wiki/Clinical_trial https:// www.nlm.nih.gov/medlineplus/clinicaltrials.html http://www.centerwatch.com/clinical-trials / http:// www.ijrpc.com/files/36-297.pdf http:// www.ich.org/products/guidelines/efficacy/efficacy-single/article/general-considerations-for-clinical-trials.html http:// icmr.nic.in/bioethics/cc_biothics/presentations/haryana/session11.pdf

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