The document discusses clinical trials, providing three key points: 1. Clinical trials are experiments conducted on human participants to evaluate new medical treatments and answer specific questions about interventions. They generate data on dosage, safety, efficacy and onset of action. 2. Clinical trials must receive approval from health authorities and ethics committees before being conducted to ensure the risk-benefit ratio is adequately vetted. Approval does not guarantee a therapy is safe or effective. 3. The document then outlines the different phases of clinical trials, from initial small-scale Phase I trials to evaluate safety, to larger Phase III trials to determine efficacy compared to existing standard treatments under controlled conditions.

1. Biostatistics
assignment
Clinical
trial Nidahira ch
21375038
Stat -
428

2. • Clinical trials are experiments or observations done in clinical research. Such prospective biomedical or behavioral
research studies on human participants are designed to answer specific questions about biomedical or behavioral
interventions, including new treatments (such as novel vaccines, drugs, dietary choices, dietary supplements, and
medical devices) and known interventions that warrant further study and comparison.
• Clinical trials generate data on dosage, safety, onset action* and efficacy*. They are conducted only after they have
received health authority/ethics committee approval in the country where approval of the therapy is sought. These
authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is
'safe' or effective, only that the trial may be conducted.
CLINICAL TRIALS
Efficacy ability to produce a desired result
Onset action the time it takes for a medicine to
start to work

3. DEFINITION (CLINICAL TRIAL)
A prospecture study comparing the
effect of intervention(s) against a
control in human beings.
A clinical trial participant receives
an injection
In the definition of clinical trials, there are some word
which meaning in medical field is :
• Prospective from now to forwarded time
• Retrospective form now to back warded
time
• Intervention the word itself contain some
terms or process or test which
help the word intervention to
complete the definition

4. INTERVENTIONS

5. Double blind if neither the physician nor the
patient knows what treatment he
or she is getting.
Single blind if the patient is blinded as to
treatment assignment but the
physician is not.
Unblinded if both the physician and patient
are aware of the treatment
assignment.

6. TYPES OF CLINICAL TRIALS
• Pilot studies and feasibility studies
• Prevention trials
• Screening trials
• Treatment trials
• Multi-arm multi-stage (MAMS) trials
• Cohort studies
• Case control studies
• Cross sectional studies

7. PHASES OF CLINICAL TRIALS

8. • The main goal is to identify(find) the safest dose and
to observe the side effects of a new drug.
• The Maximum Tolerance Dose (MTD) will be achieved
• Divide subjects into small cohorts.
• The duration of this phase will be up to one month.
• Unblinded and uncontrolled phase.
• The sample size will be in between 20 to 80 patients.
• If the new drug is found safe then it is considered
worthy for further study.
• For example, the study of a single dose of drug 'X’ in
normal subjects
PHASE I
Uncontrolled not confined to particular age
group

9. PHASE II
• The main objective of this phase is to evaluate effectiveness
and to identify common risks for a specific population and
disease.
• Drug-Disease interactions, safety of a patient and efficacy at
various doses are the key factors.
• The focus is to see the dose - response and tolerance,
adverse effects and efficacy.
• This phase contains two components i.e., phase IIA and IIB.
• Phase IIA, the effectiveness of the drug / treatment is
determined. If it is found effective, we proceed to IIB; else
stop.
• Phase IIB, is used to estimate the therapeutic effectiveness
of the drug.
• Around 200 to 300 patients are involved.

10. PHASE III
• In this phase also, drug-disease interactions, dosage intervals
efficacy and safety for subgroups are identified.
• The design features consists of randomized controlled experiments.
• It will take several years to complete and to move to next phase.
• Individuals will be with target disease, where few of them will
receive standard treatment and the remaining will receive standard
treatment and the remaining will receive new treatment which is
under study.
• This phase needs some planning and design such as time, number
of treatments, duration, treatment allocation ratio and so on.
• The number of patients usually ranges from hundreds to thousands.
• In this phase, major importance is given to statistical techniques
• Comparative study of drug 'X' versus standard treatment.
Comparative trial (intervention(s) vs control)

11. PHASE IV
• It is about the survivalance studies or post-marketing research
about a new drug which has been approved for marketing.
• This phase is processed either in hospitals or general practitioners
following the guidelines of Good Clinical Practice (GCP).
• The outcomes of this phase are monitored to collect data to
address issues that support product success in a real world clinical
practice. It is about the survivalance studies or post-marketing
research about a new drug which has been approved for marketing.
• The main reasons for processing this phase are to find out the side
effects and safety of the drug, risks and benefits in long term use of
drug.
• To observe how well the drug works when it is used more widely in
clinical practice.
• After obtaining approval from FDA, phase IV of a clinical trial will
commence.
• Observed in larger population
FDA food and drug administration (association)

13. THE
LOGICAL
PROCESS
OF
A
CLINICAL
TRIAL

14. DIFFERENCE BETWEEN IN VIVO AND IN VITRO STUDIES
Clinical trial falls under in vivo studies

15. Sometimes observational study evidence can lead to misleading conclusions about the efficacy or safety of a treatment, only to
be overturned by clinical trials evidence, with enormous public health implications. The Women’s Health Initiative (WHI) clinical
trial of hormone therapy is a dramatic example of that.21 Estrogen was approved by the FDA for relief of post-menopausal
symptoms in 1942, aggressively marketed in the mid 1960’s, and after 1980, generally combined with progestin for women
with a uterus because it was found that progestin offset the risks of estrogen for uterine cancer. In the meantime many large
prospective follow-up studies almost uniformly showed that estrogen reduced heart diseases by 30-50%. In the 1993 WHI
mounted a large clinical trial to really answer the question of long-term risks and benefits of hormone therapy. One part was
the study of estrogen alone for women had had a hysterectomy, and thus didn’t need progestin to protect their uterus, and
another part was of estrogen plus progestin (E+P) for women with an intact uterus. The E+P trial was a randomized, double
blind, placebo-controlled clinical trial meant to run for an average of 8.5 years. It included 16,608 women ages 50-79; such a
large sample size was deemed necessary to obtain adequate power. The trial was stopped in 2002, three years before its
planned completion, because the Data and Safety Monitoring Board or DSMB, (as described in Chapter 9) found estrogen plus
progestin caused an excess of breast cancer, and surprisingly, there was a significant and entirely unexpected excess of heart
attacks in the E+P group compared to placebo! Final results, reported in subsequent papers, showed that the adverse effects (a
24% increase in invasive breast cancer, 31% increase in strokes, 29% increase in coronary heart disease and more than a two-
fold increase in pulmonary embolism and in dementia) offset the benefits, (a 37% decrease in colorectal cancer and 34%
CLINICAL TRIAL AS “GOLD STANDARD”
The Gold Standard of clinical research is the randomized double-blind study, in which patients are assigned to
treatments at random and neither the patient nor the physician is aware of the treatment assignment.

16. Why such different results from a clinical trial than from observational longitudinal studies? The most likely explanation is
selection bias. Women who were taking hormones and then followed to observe their rates of heart disease, were in virtually
all the observational studies, healthier, thinner, more active, more educated, less overweight, than their non-hormone taking
counterparts, and their healthier lifestyle and better baseline health status, rather than the hormones per se, was what
accounted for their lower rates of heart disease.
The question now is answered using the “gold standard” the clinical trial: estrogen plus progestin does not protect against
heart disease, and in fact increases the risk. As noted before, the impact of this research is great since so many millions of
women were using the preparation tested

17. EXAMPLE
The sanocrysin treatment founded in 1923 for pulmonary tuberculosis
Purpose to reduce inflammation and also to slow the disease progression
Observation 1. side effect: itching, skin discoloring
2. efficacy : limited
3. onset action: very slow
There is a study on rabbit and monkey by giving or injecting the doses of 2mg, 1.5mg and
3mg sanocrysin drugs to check the tolerance

18. THANK YOU