Clinical trials helps in the discovery and development of drugs which helps to improve health, drug discovery and development is a key aspect of medicine which ensure more improved drugs are been developed to improve health in the society

1. CLINICAL PHASE OF DRUG
DEVELOPMENT
DR. ORUBU C.O.
DEPARTMENT OF PHARMACOLOGY & THERAPEUTICS,
FACULTY OF BASIC MEDICAL SCIENCES,
DELTA STATE UNIVERSITY,
ABRAKA.

2. DAY 1

3. Drug development
Logical stepwise procedure in which information from early
studies is used to support and plan larger, more definitive
What is clinical trial?
Clinical trial is a systematic investigation in human subjects for
evaluating the safety and efficacy of any new drug.
Clinical trials are a set of tests that generate safety and
efficacy data for health interventions in human beings.

4. Clinical Trials are conducted only when
 Satisfactory information has been gathered on the quality of nonclinical
safety
 Health authority/ethics committee approval is granted in the country
where approval of the drug is sought.
Clinical trials,
 It is the mainstay for bringing out new drugs to the market.
 It answers critical research questions
 Find better treatments and ways to prevent disease
 Translate results of basic scientific research into better ways to prevent,
diagnose, or treat disease.

5. DRUG REVIEW STEPS
 Preclinical testing.
 An Investigational new drug (IND) application: Outlines what the
sponsor of a new drug proposes for human testing in clinical trials.
 Phase I studies
 Phase II studies
 Phase III studies
 Submission of New Drug Application (NDA) is the formal step asking the
FDA to consider a drugs for marketing approval.
 FDA reviewers will approve the application or find it not approvable.
 Phase IV: post-market surveillance

6.  The need for a structured regulation of drug development became evident in
the late 1950s and early 1960s following the discovery of phocomelia, a
congenital deficits that occurred following the use of Thalidomide. This was
marketed in Germany in 1957 as an over-the-counter drug for sleeplessness
(insomnia), cold and cough as well as morning sickness in pregenancy. It was
marketed as a ‘drug with safety profile’ for everyone, including pregnant
mothers and child. Animal studies were found to be safe but safety studies
on human were not preformed.
 Currently, it takes over 10 years in general for patent filing, through the pre-
clinical, clinical and then marketing phase.

8. DRUG REVIEW
 Before one can initiate testing in human beings, extensive preclinical or
laboratory research is required
 Research usually involves years of experiments in animal and human
cells.
 If this stages of testing is successful, the sponsor then approves this data
to the FDA requesting approval to begin testing in humans. This is called
an Investigational New Drugs (IND) Application.
 If approved by the FDA, testing in humans begins. This is done through
a formally written and approved protocol.

9. SOME ETHICAL ISSUES
Declaration of Helsinki
 The World Medical Association (WMA) has developed the Declaration of
Helsinki as a statement of ethical principles to provide guidance on
medical research involving human subjects. Medical research involving
human subjects includes research on identifiable human material or
data.
 The Declaration of Helsinki was adopted in 1964 by the 18th WMA
General Assembly, at Helsinki, the Capital of Finland.
 This declaration has been amended 7 times, with the current version
being that of 2013.
 Other versions include that of 1975, 1983, 1989, 1996 and 2008 which are
no longer referenced.

10. Declaration of Helsinki
Issues addressed in the Declaration include;
 Research with humans should be based on results from laboratory and
animal experimentation
 Research protocol should be reviewed by an independent committee
prior to initiation.
 Informed consent from research participants is necessary.
 Research should be conducted by medically/ scientifically qualified
individuals.
 Risk should not exceed the benefits.

11. Declaration of Helsinki
 The seventh revision added new rules designed to protect patients in
research studies, including provisions to compensate people who have
been harmed by their participation in medical research and to expand
their access to beneficial treatments that result from the study.

12. The Four Principles of Ethics
These include
 Autonomy
 Beneficence
 Non-malfeasance
 Justice
Although, they do not provide ordered rules, these principles help
doctors and other health related personnel to make decisions when
reflecting on ethical issues during clinical trials.

13. Autonomy
 This simply means respect for a patient in a clinical setting.
 All persons have intrinsic and unconditional worth, and therefore,
should have the power to make rational decisions and moral choices,
and each should be allowed to exercise his or her capacity for self-
determination.
 Every human being of adult years and sound mind has a right to
determine what shall be done with his own body.
 One can choose not to take part in a clinical trial.

14. Beneficence
 The principle of beneficence is the obligation of physician to act for the benefit of
the patient.
Non-maleficence
 Nonmaleficence is the obligation of a physician not to harm the patient. This
principle supports several moral rules – do not kill, do not cause pain or
do not incapacitate, and do not deprive others of the goods of life. The practical
application of nonmaleficence is for the physician to weigh the benefits against
burdens of all interventions and treatments, to eschew those that are
inappropriately burdensome, and to choose the best course of action for the
patient.

15. Justice
 Justice is generally interpreted as fair, equitable, and appropriate
treatment of persons.
 Of the several categories of justice, the one that is most pertinent to
clinical ethics is distributive justice.
 Distributive justice refers to the fair, equitable, and appropriate
distribution of health-care resources determined by justified norms.

16. STAGES OF DRUG DEVELOPMENT

17. PHASES OF CLINICAL TRIALS

18. PHASE 0 (MICRO-DOSING STUDIES)
 New viable tool in drug development
 Small sample size of 10 -15 subjects is required
 By definition, FDA –
“Use of 100 mcg of candidate drug or less than
1/100th of the pharmacological dose determined
from the animal models and in-vitro systems using
the test substance”

19. Why conduct micro dose studies ??
 To obtain information on human pharmacokinetics as early as possible.
 Compares absorption, distribution, metabolism and excretion (ADME)
parameters for several drug candidates where animal data may be
conflicting
 Helps in selecting the first dose for a Phase I study
 Validate animal model for pharmacology and toxicology
 Pharmacoeconomics – Cost benefit analysis

20. Goal of Phase 0 studies
 To assess whether the mechanism of action defined in pre-clinical studies
is achieved or not
 Determine special methods to assess the pharmacokinetics of the drug
 Develop novel models to evaluate the pharmacodynamic data prior to
phase I

21. Advantages of micro dosing
 Requires minute quantities of drug – not intended to produce any
pharmacological effect; risk of adverse events less
 Decreases time of drug development decreases cost significantly
 Reduces animal testing
 Helps patients and industry with earlier availability of test drugs

22. Limitations of micro dosing
 Insufficient information on body’s reaction to micro dose and
pharmacological dose
 Micro dosing may not predict kinetic parameters accurately
for drugs showing non-linear kinetics