Experimental study- Clinical trials

1. Experimental study /
Clinical trials
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2. What is Experiment?
• Experiment is a procedure carried out by researcher by manipulating
an object and observing the result of that manipulation.
The experiment can be pursued for various reasons:
• to test a hypothesis to offer an explanation for the phenomenon/ phenomena,
• to answer the “what if” question without expecting concrete results in
relation to what the experiment will show, or
• to confirm results of previous studies.

3. Design of experiment
• Experiment provides insight into cause-and-effect by demonstrating
which outcome occurs when a particular factor is manipulated.
• Well designed experiment include the independent variable which is
manipulated by the experimenter, and the dependent variable which is
measured.
• Experiments typically include controls, which are designed to minimize
the effects of other than the single independent variable, in order to
increase a reliability of the results.

4. What is an Experimental study?
Definition.
• Experimental study is a type of research in which a researcher performs
an intervention or artificially manipulates study factors or subjects in
order to reveal the effect of this manipulation.
• Experimental study allows cause and effect to be determined. The
manipulation of variables allows for researchers to be able to look at
various cause-and-effect relationships that a product, theory, or idea can
produce.

5. Purpose.
• The purpose of experimental study is to determine the causal effect of a certain
factor (on a certain effect). To do this, researcher involves the random
assignment (distribution) of study participants into two different groups
experimental group and control group.
• In other words, the purpose of experimental research is to determine the
relationship between two variables (dependent and independent). This
relationship is generally causal in nature.
• The data collected in experimental research has to be numeric or quantified. It
must be measurable, capable of statistical analysis, and comparable; so,
experimental research is quantitative in nature.

6. Some definitions to remind:
Dependent Variable
• Variable that is expected to be dependent on the manipulation of the independent
variable
• Criterion by which the results/outcome of the experiment are measured and judged
Independent Variable
• Variable that can be manipulated or changed independently of any other variable
• Variable that studied in research where causal effects are suspected

7. Experimental studies characteristics
There are three essential characteristics of experimental studies,
namely:
1. Looks at cause-and-effect relationship
2. Is highly controlled, objective, systematic study
3. Involves the measurement of independent and dependent variables

8. Relevance of experimental studies in the field of medicine
• Compared to the observational studies, experimental studies are considered the
gold standard in biomedical and social research, because researchers are able to
determine causal effects with most confidence than when using any other
research method.
• Applications of the experimental studies design:
The classical application of the experimental design to studies of human
populations is the clinical trial of the efficacy of a new drug or treatment
methods.
Other application of the experimental studies is to the testing of hypotheses
about the etiology of a disease, prevention and safety issues which are
already tested and corroborated from various forms of observational studies
(e.g. cohort studies).

9. Experimental study design
A true experimental study design must consist of the following three
characteristics:
• Manipulation
• Randomization
• Control

10. Brief glossary of terms
• Manipulation - is a conscious act of the researcher in which the researcher varies
the independent variables and then observes how the manipulation affects the
dependent variables of interest.
• Control - refers to use a control group in experiment for controlling the effect of
extraneous variables on the dependent variables in which researcher is
interested.
• Randomization - means that every subject has an equal chance being assigned
to experimental or a control groups on a random basis. Through randomization
the chances of systemic bias as well as the effect of extraneous variables on the
depended variables is eliminated.

11. Control in experimental studies
Purpose of control.
• Control in an experiment is designed to minimize the effects of variables other
than the independent variable. This increases the reliability of the results, often
through a comparison between control measurements and the other
measurements.
• There are three key elements of a well designed experiment: the control should
be carried out in the following directions:
I. Control for influential factors
II. Control for precision of distribution of subjects of the study
III. Control for correct replacement and constant errors

12. I. Control for all influential factors
The factors that may influence an experiment may be:
• Confounding variable - occurs when an experimenter cannot tell the difference
between the effects of different factors on a variable (e.g. what was the cause - junk food
or stress?)
• Extraneous variables - variables other than the manipulated variables that affect the
results of the experiment; can potentially invalidate the results
• Placebo effect - occurs when an untreated subject incorrectly believes that he/she is
receiving a treatment and reports an improvement in symptoms occurs when a subjects
acting favorable to a placebo even when they received no medication.
(Placebo – is an artificial treatment that looks like the real treatment (i.e. sugar pill). In clinical trials it
acts as a control factor)

13. II.a) Control for precision of subjects’ distribution –
randomization and blinding
Randomization
• Assignment of subjects and treatments to groups is
based on chance, so all individuals have equal
opportunity to be involved in study
• Provides “control by chance”
• Random assignment allows the assumption that the
groups are identical
with respect to all variables except the experimental
treatment
• Randomization is provided using computer, or coins,
dice or cards.

14. II.b) Control for precision of subjects’ distribution –
randomization and blinding
Blinding is a technique used:
• to control subjects’ knowledge of whether or not they have been given
the experimental treatment.
• tasting samples, placebos (chemically inert pills), etc.
Level of blinding:
• single-blind (participants do not know if they are receiving treatment or not),
• double-blind (neither participant nor doctor do not know about that), and
• triple-blind (in addition, also the institution which conducts study does not know
what are in the packages received from the pharmaceutical company for
studying)

15. III. Control for correct replacement and constant errors
Replacement:
• The repetition of an experiment using a large group of subjects.
• Have large group size!
Constant error - is error that occurs in the same experimental condition every
time the basic experiment is repeated, also called a systematic bias.

16. Ethical issues in experiment /clinical trial
• General moral principles in research with human and animal beings, defined
by the "Nuremberg Code“, deal with strict criteria for approval, endorsement
and evaluation of a clinical trial.
• Ethical considerations and requirements for consent of the experimental
subjects are of primary concern in the clinical trials, and those concerns set the
first and final limits for implementing a trial.

17. Experimental methods used in
medical investigations

18. Experimental research methods include:
• Clinical trials
• Randomized controlled trial

19. Clinical trials
• Clinical trial is a branch of healthcare science that determines the safety and
efficacy of medications, medical devices, diagnostic products and treatment
regimens intended for human use.
• Clinical trial is different from clinical practice. In clinical practice established
treatments are used, while in clinical trial evidence is collected to establish a
treatment.

20. Definition of clinical trials
• Definition. The term "clinical trial“ refers to the entire history of elaboration of a
drug (or device, or biologic test) from its inception in the laboratory to its
introduction to the consumer market and beyond.
• Process. After the promising candidate of drug or the molecule is identified in the
laboratory, it is subjected to pre-clinical studies or animal studies that examine
different aspects of an investigational drug test article are studied on the basis of
successive stages /phases.
• Clinical trial is often conducted at academic medical centers and affiliated
research study sites. These centers and sites provide the prestige of the academic
institution as well as access to larger metropolitan areas, providing a larger pool
of medical participants. These academic medical centers also oversee the ethical
conduct of medical trials.

21. Types of clinical trials
• The National Institute of Health (NIH), which is the primary organization
responsible for health related research, classifying clinical trials by their
purpose as follow:
Prevention clinical trials
Screening clinical trials
Diagnostic clinical trials
Treatment clinical trials

22. Types of clinical trials
Prevention clinical trials - are experimental research methods for looking for
better techniques to prevent disease. This include testing a methods to prevent
or lower the chances of contracting the disease in the future.
• An example is the Breast Cancer Prevention Trial (BCPT) (by National Cancer Institute,
USA) in where 13,000 women aged 35 or over were recruited to test whether taking the
drug tamoxifen can prevent breast cancer in women who are at an increased risk of
developing the disease.
Screening clinical trials – experimental research methods designed to develop
and assess screening tool to detect certain disease. and to detect whether finding
certain health conditions before symptoms emerge would help the treatment of
the disease.
• An example is the set of trials of number of screening tests including imaging tests, lab
tests and genetic tests elaborated by National Cancer Institute and widely used worldwide.

23. Types of clinical trials
Diagnostic clinical trials are research methods that surround developing tools that
can be used for recognizing or detecting a particular disease.
• An example is the imaging technologies to lung cancer such as magnetic resonance imaging
(MRI) or computed tomography (CT) provide researchers with information on changes in the
anatomy, but recently researchers have found that positron emission tomography (PET)
imaging, which uses biochemical processes, may be able to detect lung cancer before
anatomical changes occur.
Treatment clinical trials - are research methods that are used to test new drugs or
new combination of drugs, new treatments, or new types of surgery.
• For example, in the treatment of cancer, there are treatment trials being carried out, in terms
of a new drug to treat cancer, new approaches of surgery and new types of radiation
treatment.

24. Clinical trials
The use of clinical trials was first introduced the year 1025,
in the Canon of Medicine (The Law of Medicine) which was
14-volume medical encyclopedia written in Arabic by
scientist and physician Avicenna (Abu Ali ibn Sino, 980–
1037).
In this encyclopedia Avicenna wrote guidelines for
investigating and examining the effectiveness of new
medical drugs which still forms the basis of many modern
clinical trials.

25. Clinical trial design
Compare between groups
Compare Compare
within groups within groups
Compare between groups
Time 2:
Experimental group
of participants
after
treatment
Time 2:
Control group of
participants
after still not
receiving treatment
Time 1:
Experimental group
of participants
before
treatment
Time 1:
Control group of
participants at same time
before
experimental group is
treated
t

26. Type of clinical trial - Randomized control trials
• Randomized control trials (RCTs) are clinical trials that involve the approval
process for new drugs. They are most often used in all types of clinical studies
described above.
• Randomized control trials are the research designs that are considered to be of
a high quality standard, as it can provide researchers with some of the strongest
evidence that the treatment or intervention has had the expected effect on
treatment outcomes.

27. Phases of clinical trials (RCT)
Randomized control trials (RCT) are commonly classified into four phases (I, II, II, IV)
Characteristics of RCT:
o The process of drug-development will normally proceed through all four
phases.
o Each phase of the drug approval process is treated as a separate clinical trial.
o Each phase provide evidence to the next phase.
o If the drug successfully passes through phases I, II, and III, it will usually be
approved by the national regulatory authority for use in the general
population; phase IV are 'post-approval' studies.

28. Phases of clinical trials
Phase I.
- The purpose is to study the safety and dosage of new drug
- Includes 10-20 (up to 100) healthy volunteers.
- Typically lasts several months.
- Usually 70% of drugs advance to the next phase.
_________________________________________________
Phase II.
-The purpose is to look at the effectiveness of treatment.
- Includes larger number of participants – patients, ranging 100-300.
- Duration may be several months or years.

29. Phases of clinical trials (cont’d)
Phase III.
- The purpose is to test new treatment against existing standard treatments.
- Includes approximately 1,000-3,000 participants to collect more data about
narrow characteristics the drug.
- Duration may be several years.
_____________________________________
Phase IV.
- Used to further evaluate long-term safety and effectiveness of new treatment
- Usually takes place after drug is approved
- Is provided in different setting and called 'post-approval'/‘post-marketing’
studies

30. Phases of clinical trials

31. Process of clinical trials
General issues to consider:
- Clinical trial protocol
- Ethical consideration
- Informed consent
- Clinical trial design
- Releasing results

32. Clinical trial protocol
This is a written, detailed action plan that:
• Provides background about the trial
• Specifies trial objectives
• Describes trial’s design and organization
• Ethical consideration
• Institutional board approval
• Ensures that trial procedures are consistently carried out, focuses on:
• Minimize risks
• Ensure data integrity and control, to minimize biases and errors
• Releasing the results of clinical trials
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33. Ethical consideration
Ethical consideration is the set of relevant ethics considered in the conduct of
a clinical trial in the field of clinical research. It borrows from the broader fields
of research ethics and medical ethics.
Ethical consideration means that participants in clinical research have rights which
they should expect, including:
right to informed consent
shared decision-making
privacy for research participants
return of results
right to withdraw

34. Informed consent
• Informed consent is a process for getting permission before conducting a
healthcare intervention on a person, or for disclosing personal information.
• Informed consent is strictly required for all clinical trials. A health care
provider may ask a patient to consent to receive therapy before providing it, or
a clinical researcher may ask a research participant before enrolling that person
into a clinical trial.
• Informed Consent Form Templates can be found on the World Health
Organization (WHO) website for practical use.

35. Clinical trial design
Well designed clinical trails should be based on:
• Eligibility criteria.
• Can range from general (age, sex, type of cancer) to specific (prior
treatment, tumor characteristics, blood cell counts, organ function)
criteria. Eligibility criteria vary with trial phase and protocol.
• Endpoint.
• Measurable outcome that should indicate an effectiveness of
intervention. Should be described carefully in protocol.
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36. Releasing the results of clinical trials
 Published in peer-reviewed journals
 Public announcements
 Results not made public until end of trial
 Add in the existing guideline or elaborate the new one
 Once proven safe and effective in a clinical trial, an
intervention may become the new standard of care
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37. Barriers, benefits and risks
of participation in clinical trials

38. Barriers to participation in clinical trials
By the physician
Physicians may:
• Be unaware of appropriate trials
• Be unwilling to lose control of patient’s care
• Believe that standard therapy is best
• Believe that clinical trials are more work
• Worry on how the person will react to suggestion of clinical trial
participation
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39. Barriers to participation in clinical trials
By the patient
Patients may:
• Be unaware of clinical trials
• Lack access to trials
• Fear, distrust, or be suspicious of research
• Have practical or personal obstacles
• Face insurance or cost problems
• Be unwilling to go again

40. Benefits and risks of participating in clinical trials
Benefits
• Early access to new treatments
• Active role in own health care
• Participation in advancing medical
knowledge
Risks
• New treatments are not always
better than standard care
• Unexpected side effects
• May not work for everyone
• Additional cost
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41. Thank you!

42. References
1. J. Maltby et al. Research methods for Nursing and Healthcare.4’th edition. Sage.
2. John W. Creswell. Research design. Qualitative, Quantitative and Mixed Methods
Approaches.4th edition. Sage