the slide is about basic concept of the clinical trials

1. Features of clinical trials
By Drashti Patel
(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 Committee
 Recent scenario
 Conclusion

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?
1. Patient / Healthy volunteer
2. Clinical Pharmacologist, Clinical Investigator & team:
[Qualified and competent]
3. Institution where trials are held : [Approval required]
4. Ethical Review Board or Institutional Ethical
Committee:
5. Sponsor
6. 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
There 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.
 All 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 (Vioxx)

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:
1. To protect the dignity, rights & well being of patients /
volunteers
2. Ensure a competent review of the protocol
3. Advise on all aspects of welfare & safety
4. 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.
 And the total time taken for drug development
constitutes 7-10 years.

22.  According to the latest estimates made by the Tufts
Centre 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. Conclusions
 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.pd
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25. THANK YOU