A

PROJECT REPORT OF
REVIEW OF CLINICAL TRIALS

SUBMITTED IN
PARTIAL FULFILLMENT OF THE REQUIREMENTS
FOR THE DEGREE OF
BACHELOR OF PHARMACY

MANIK MAKANI

Registration No. PIET-BPH-2028

Supervisor: Mrs. Arti Soni

Department of Pharmacy

Panipat Institute of Engineering and Technology

Samalkha (Panipat) 132102

Affiliated to
Pt. B.D. SHARMA UNIVERSITY OF HEALTH SCIENCES, ROHTAK (HARYANA)
 DECLARATION

I hereby declare that the work reported in the project entitled “Review of Clinical Trials” has been
carried out by me under the supervision of Mrs. Arti Soni at Department of Pharmacy, Panipat
Institute of Engineering and Technology (Panipat) during the academic session 2023- 2024.

Place: PANIPAT MANIK MAKANI

Date: PIET-BPH-2028

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 CERTIFICATE

This is to certify that the project entitled “Review of Clinical Trials” has been carried out by
Mr. Manik Makani under my supervision at Department of Pharmacy, Panipat Institute of
Engineering and Technology, Samalkha, Panipat, Haryana during the academic session 2023- 2024.
He/ She has attended the stipulated number of days as per the prevailing rules.

Mrs. Arti Soni

Supervisor
Designation
Department of Pharmacy

Seal with date

Forwarded by:
Dr. Gaurav Agarwal
Principal

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 ACKNOWLEDGEMENT

At the start of every major task, initially difficulties seem overwhelming. But gradually, as we commence
gaiting on the chosen tract authentically and perseverance finding the presence of Almighty helping us at
every step we look. I have taken efforts in this project. However, it would not be possible without the
kind support and inspiration of many individuals. I would like to extent my sincere thanks to all of them I
am extremely thankful to Dr. Gaurav Agarwal, Principal, Panipat Institute of Engineering and
Technology (Panipat) pursue this research work with great ease. It is with Plum bless gratitude that
expresses my benevolent to my guide Mrs. Arti Soni, Associate Professor, Panipat Institute of
Engineering and Technology (Panipat), Haryana for permitting me to undertake dissertation under his
able guidance. I would like to express my special thanks of gratitude to my parents for giving
encouragement and invaluable assistance tone that enabled me to complete this work on time finally. I am
grateful to all those who helped me directly and indirectly to achieve this goal, to all those whom I have
not been able to express gratitude as an individual.

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 CONTENTS

S. No. Contents Page No.

1. Introduction

2. Literature Review

3. Aim and Objectives

4. Materials and Methods

5. Results and Discussion

6. Summary and Conclusion

7. Bibliography

List of Tables

List of Figures

List of Abbreviations and Symbols

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THE DAY WHERE IT ALL STARTED………

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NEW DRUG DEVELOPMENT: REVIEW OF CLINICAL
TRIALS

INTRODUCTION

Clinical trials, also known as clinical

studies, are research studies in which
scientists and doctors test new drugs
and treatments to see if they will
improve health. Many of today's
treatments for cancer are based on the
results of past clinical trials. Because of
progress made through clinical trials,
many people treated for cancer are now
living longer.
Clinical trials are divided into four phases.

WORLD HEALTH ORGANISATION DEFINITION

According to the World Health Organisation (WHO), a clinical trial is ' Any
research project that prospectively assigns human participants or groups to
one or more health- related interventions to evaluate the effects on health
outcomes.

CLASSIFICATION OR DIFFERENT TYPE OF CLINICAL TRIAL

There are several types of clinical trials:
 Prevention trials test new approaches, such as medications, vitamins, or
other supplements, that doctors believe may lower the risk of developing
a certain type of cancer. Most prevention trials are conducted with
healthy people who have not had cancer. Some trials are conducted with
people who have had cancer and want to prevent recurrence (return of
cancer), or reduce the chance of developing a new type of cancer.
 Screening trials study ways to detect cancer earlier. They are often
conducted to determine whether finding cancer before it causes
symptoms decreases the chance of dying from the disease. These trials
involve people who do not have any symptoms of cancer.
 Diagnostic trials study tests or procedures that could be used to identify
cancer more accurately. Diagnostic trials usually include people who have
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 signs or symptoms of cancer.

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 Treatment trials are conducted with people who have cancer. They are
designed to answer specific questions about, and evaluate the
effectiveness of, a new treatment or a new way of using a standard
treatment. These trials test many types of treatments, such as new
drugs, vaccines, new approaches to surgery or radiation therapy, or new
combinations of treatments.
 Quality-of-life (also called supportive care) trials explore ways to improve
the comfort and quality of life of cancer patients and cancer survivors.
These trials may study ways to help people who are experiencing
nausea, vomiting, sleep disorders, depression, or other effects from
cancer or its treatment.

DESIGNING OF CLINICAL TRIAL OBJECTIVES

Before going detailing into the other aspects of clinical trial, it is a must to
know about the several aspects of clinical trials like
 protocol and its development with expanded access protocol
 role of ethics
 participants criteria
 eligibility criteria
 informed consent
 placebo
 control and control group
 safety of participants
 sponsors
 place of clinical trials
 do consider before participating in a trial

1. Protocol and its development

What is a protocol?
“ A protocol is a study plan on which all clinical trials are based. The plan is carefully
designed to safeguard the health of the participants as well as answer specific
research questions. A protocol describes what types of people may participate in the
trial; the schedule of tests, procedures, medications, and dosages; and the length of
the study. While in a clinical trial, participants following a protocol are seen
regularly by the research staff to monitor their health and to determine the
safety and effectiveness of their treatment.”

-For example, the protocol includes:

o The reason for doing the trial
o How many people will be in the trial
o Who is eligible to take part in the trial
o What study drugs participants will need to take
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 o What medical tests participants will have and how often
o What information will be gathered
Protocols are written by the trial sponsors (those conducting the trial)
and must first be reviewed by an Institutional Review Board (IRB) at each
participating hospital or medical centre before they can begin. IRBs are
committees that oversee the safety of people who take part in clinical
trials.
2. ETHICS COMMITEES
Research Ethics Committees (RECs) are independent groups, founded
and governed by local Health Authorities or the Department of Health.
Research cannot be started until the Research Ethics Committees has given
its approval.
Researchers must consider the ethical implications and psychological
consequences for the participants in their research. Threats to their
psychological well-being, health, values or dignity should be removed.
 The researcher should inform all participants of all aspects of the research.
 The withholding of information or the misleading of participants is
unacceptable if the participants are likely to object or show unease once
debriefed.
 Participants should know their right to withdraw from the research at any
time.
 Information obtained about a participant during an investigation is
confidential unless otherwise agreed in advance.
 Researchers have a primary responsibility to protect participants from
physical and mental harm during the investigation.

3. PARTICIPANTS CRITERIA
An ethics committee must approve every survey or experiment a
psychologist wishes to run. It is important to obtain ethical approval for each
survey to ensure that the questions asked are appropriate and do not cause
people offence.
Participants in psychological research should have confidence in the
researchers. They should be supplied with all the relevant information about
the study, the method of data gathering (e.g. questionnaire, computer test),
the sample group (students, children, general public) and the object of the
research.
4. ELIGIBILITY CRITERIA
Each study protocol has guidelines for who can or cannot participate in the
study.
These guidelines, called eligibility criteria, describe characteristics that must
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be shared by all participants. The criteria differ from study to study. They
may include age, gender, medical history, and current health status.
Enrolling participants with similar characteristics helps to ensure that the
results of the trial will be due to what is under study and not other factors. In
this way, eligibility criteria

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help researchers achieve accurate and meaningful results. These criteria also
minimize the risk of a person condition becoming worse by participating in
the study.

5. CONSENT
Informed consent is a process by which people learn the important facts
about a clinical trial to help them decide whether to participate. This
information includes details about what is involved, such as the purpose of
the study, the tests and other procedures used in the study, and the possible
risks and benefits. In addition to talking with the doctor or nurse, people
receive a written consent form explaining the study. People who agree to
take part in the study are asked to sign the informed consent form. However,
signing the form does not mean people must stay in the study. People can
leave the study at any time" either before the study starts or at any time
during the study or the follow-up period.
The informed consent process continues throughout the study. If new
benefits, risks, or side effects are discovered during study, the researchers
must inform the participants.
They may be asked to sign new consent forms if they want to stay in the study.
6. PLACEBO
A placebo is an inactive pill, liquid, or powder that has no treatment value.
In clinical trials, experimental treatments are often compared with placebos
to assess the experimental treatment's effectiveness. In some studies, the
participants in the control group will receive a placebo instead of an active
drug or experimental treatment.
7. CONTROL OR CONTROL GROUP
A control is the standard by which experimental observations are
evaluated. In many clinical trials, one group of patients will be given an
experimental drug or treatment, while the control group is given either a
standard treatment for the illness or a placebo.
8. SAFETY OF PARTICIPANTS
During the trial, review committees such as Institutional Review Boards
(IRBs), make sure that the plan is being followed and participants are being
protected. Researchers performing studies are required by law to inform
patients about a study's treatment and their possible benefits and risks
before a patient decides whether to take part in the study. This process is
called informed consent
The ethical and legal codes that govern medical practice also apply to
clinical trials. In addition, most clinical research is federally regulated with
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built in safeguards to protect the participants. The trial follows a carefully
controlled protocol, a study plan which details what researchers will do in the
study. As a clinical trial progresses, researchers report the results of the trial
at scientific meetings, to medical journals, and to various government
agencies. Individual participants' names will remain secret and will not be
mentioned in these reports

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 9. SPONSORS
Government agencies, such as the National Cancer Institute (NCI) and other
parts of the National Institutes of Health (NIH), the Department of Defence,
and the Department of Veterans Affairs, sponsor and conduct clinical trials.
In addition, organizations or individuals, such as physicians, medical
institutions, foundations, volunteer groups, and pharmaceutical companies,
also sponsor clinical trials.
NCI sponsors a large number of clinical trials and has a number of programs
designed to make clinical trials widely available in the United States. These
programs include the following:
 The Cancer Centres Program provides support to research-oriented
institutions, including those that have been designated as NCI
Comprehensive or Clinical Cancer Centres for their scientific excellence.
 The Specialized Programs of Research Excellence (SPOREs) bring together
scientists and researchers to design and implement research programs
that can improve prevention, detection, diagnosis, and treatment of
specific types of cancer. More information about SPOREs is available on
the Internet.
 The Cancer Trials Support Unit (CTSU) makes NCI-sponsored phase III
treatment trials available to doctors and patients in the United States and
Canada . Doctors who are not affiliated with an NCI-sponsored Clinical
Trials Cooperative Group (see above) must complete an application
process, which includes credential verification and site preparedness
assessment, to become members of the CTSUs National Network of
Investigators.
 The Community Clinical Oncology Program (CCOP) makes clinical trials
available in a large number of communities across the United States.
Local hospitals throughout the country affiliate with a cancer centre or a
cooperative group. This affiliation allows doctors to offer people
participation in clinical trials more easily, so they do not have to travel
long distances or leave their usual caregivers. The Minority-Based
Community Clinical Oncology Program focuses on encouraging minority
populations to participate in clinical trials. More information about the
CCOP can be found in the NCI fact sheet Community Clinical Oncology
Program: Questions and Answers, which is available on the Internet.

10. Places of clinical trials

Depending on the type of trial, patients may be treated at one or hundreds
of clinical sites at the same time. Clinical sites can include large specialty
treatment centres, university hospitals, local medical centres or a doctor's
office. Each patient takes part in the trial under the guidance of a team
including his/her own doctor and other health care professionals, who report
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the patient's experience back to the centre responsible for the trials' overall
coordination. Experts then use the information from all participants to see if
the treatment being tested is safe and effective.

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 Do consider before participating in a trial!
People should know as much as possible about the clinical trial and feel
comfortable asking the members of the health care team questions about it,
the care expected while in a trial, and the cost of the trial. The following
questions might be helpful for the participant to discuss with the health care
team. Some of the answers to these questions are found in the informed
consent document.
 What is the purpose of the study?
 Who is going to be in the study?
 Why do researchers believe the experimental treatment being
tested may be effective? Has it been tested before?
 What kinds of tests and experimental treatments are involved?
 How do the possible risks, side effects, and benefits in the study
compare with my current treatment?
 How might this trial affect my daily life?
 How long will the trial last?
 Will hospitalization be required?
 Who will pay for the experimental treatment?
 Will I be reimbursed for other expenses?
 What type of long-term follow up care is part of this study?
 How will I know that the experimental treatment is working? Will results
of the trials be provided to me?
 Who will be in charge of my care?

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 DIFFERENT PHASES OF CLINICAL TRIALS

(1.)Human Pharmacology (Phase I) .-

(i) The objective of studies in this Phase is the estimation of safety and
tolerability with the initial administration of an investigational new drug into
human(s). Studies in this Phase of development usually have non-
therapeutic objectives and may be conducted in healthy volunteers subjects
or certain types of patients. Drugs with significant potential toxicity e.g.
cytotoxic drugs are usually studied in patients. Phase I trials should
preferably be carried out by Investigators trained in clinical pharmacology
with access to the necessary facilities
to closely observe and monitor the Subjects.
(ii)Studies conducted in Phase I, usually intended to involve one or a
combination of the following objectives:-
(a) Maximum tolerated dose: To determine the tolerability of the dose range
expected to be needed for later clinical studies and to determine the nature
of adverse reactions that can be expected. These studies include both single
and multiple dose administration.

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(b) Pharmacokinetics, i.e., characterization of a drug's absorption,
distribution, metabolism and excretion. Although these studies continue
throughout the development plan, they should be performed to support
formulation development and determine pharmacokinetic parameters in
different age groups to support dosing recommendations.
(c) Pharmacodynamics: Depending on the drug and the endpoints studied,
pharmacodynamics studies and studies relating to drug blood levels
(pharmacokinetic/ pharmacodynamics studies) may be conducted in healthy
volunteer Subjects or in patients with the target disease. If there are
appropriate validated indicators of activity and potential
efficacy, pharmacodynamics data obtained from patients may guide the
dosage and dose regimen to be applied in later studies.
(d) Early Measurement of Drug Activity: Preliminary studies of activity or
potential therapeutic benefit may be
conducted in Phase I as a secondary objective. Such studies are generally
performed in later Phases but may be
appropriate when drug activity is readily measurable with a short duration
of drug exposure in patients at this early
stage.
(2) Therapeutic exploratory trials (Phase II).-
(i) The primary objective of Phase II trials is to evaluate the effectiveness of a
drug for a particular indication or indications in patients with the condition
under study and to determine the common short-term side-effects
and risks associated with the drug. Studies in Phase II should be conducted in
a group of patients who are selected by relatively narrow criteria leading to a
relatively homogeneous population. These studies should be
closely monitored. An important goal for this Phase is to determine the
dose(s) and regimen for Phase III trials. Doses used in Phase II are usually
(but not always) less than the highest doses used in Phase I.
(ii) Additional objectives of Phase II studies can include evaluation of
potential study endpoints, therapeutic regimens(including concomitant
medications) and target populations (e.g. mild versus severe disease) for
further studies in PhaseII or III. These objectives may be served by
exploratory analyses, examining subsets of data and by including multiple
endpoints in trials.
(ii) If the application is for conduct of clinical trials as a part of multi-national
clinical development of the drug, number of sites and the patients as well as
the justification for undertaking such trials in India shall be provided to the
Licensing Authority.
(3) Therapeutic confirmatory trials (Phase III).-
(i)Phase III studies have primary objective of demonstration or confirmation
of therapeutic benefit(s). Studies in Phase III are designed to confirm the
preliminary evidence accumulated in Phase II that a drug is safe and
effective for use in the intended indication and recipient population. These
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studies should be intended to provide an adequate basis for marketing
approval. Studies in Phase III may also further explore the dose-response

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 relationships (relationships among dose, drug concentration in blood and
clinical response), use of the drug in wider populations, in different stages of
disease, or the safety and efficacy of the drug in combination with other
drug(s).
(ii) For drugs intended to be administered for long periods, trials involving
extended exposure to the drug are ordinarily conducted in Phase III, although
they may be initiated in Phase II. These studies carried out in Phase III
complete the information needed to support adequate instructions for use of
the drug (prescribing information).
(iii) For new drugs approved outside India, Phase III studies need to be
carried out primarily to generate evidence of efficacy and safety of the drug
in Indian patients when used as recommended in the prescribing information.
Prior to conduct of Phase III studies in Indian subjects, Licensing Authority
may require pharmacokinetics studies to be undertaken to verify that the
data generated in Indian population is in conformity with the data already
generated abroad.
(iv)If the application is for the conduct of clinical trials as a part of multi-
national clinical development of the drug, the number of sites and patients
as well as the justification for undertaking such trials in India should be
provided to the Licensing Authority along with the application.
(4) Post Marketing Trials (Phase IV).- Post Marketing trials are studies (other
than routine surveillance)performed after drug approval and related to the
approved indication(s). These trials go beyond the prior demonstration of the
drug’s safety efficacy and dose definition. These trials may not be considered
necessary at the time of new drug approval but may be required by the
Licensing Authority for optimizing the drug's use. They may be of any type
but should have valid scientific objectives. Phase IV trials include additional
drug-drug interaction(s), dose-response or safety studies and trials designed
to support use under the approved indication(s), e.g. mortality/morbidity
studies, epidemiological studies etc.

 What are the potential risks and benefits of clinical trials?

>Potential benefits include:
1. Access to investigational new drugs and therapies before they are available on
the market
2. A more active role in your own health care
3. Close monitoring of your health care and any side effects
4. An opportunity to make a valuable contribution to medical research
5. Potential risks include:
6. Investigational new drugs and therapies may have unknown side effects
7. Side effects may be worse than with standard therapies
8. Even if the approach has benefits, it may not work for you
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 What is informed consent?
Informed consent is a process in which a patient learns all the key facts
about the clinical trial before deciding whether to take part. A doctor or

research nurse may explain all that

is involved. In addition, these facts will be given to you in a written consent
form that you may take home to read and discuss. The consent form will
included details about:
 Who is eligible to take part in a clinical trial?
Each study has guidelines for who can take part. These are called eligibility
criteria. Generally those who take part in the study are alike in certain
aspects such as type and stage of disease, age, gender or previous
treatments. The eligibility criteria are included in the study plan (also called a
protocol).
 What are your rights if you take part in a clinical trial?
Taking part in a study is voluntary. You may choose not to take part or may
leave the study at any time. Leaving the study will not result in any penalty
or loss of benefits to which you are entitled.
The study sponsor (those running the trial) will tell you about new
information that may affect your health, welfare, or willingness to stay in the
study.

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 Clinical Trials Research Pharmacist
The Clinical Trials Research Pharmacist (CTRP) is a licensed
pharmacist who has received his or her Doctor of Pharmacy,
and has been trained in providing pharmaceutical care to
patients enrolled in clinical trials. The advantages of utilizing
this service in clinical trials are tremendous.
The initial benefits include increased patient compliance and patient
retention.
The CTRP™ is able to provide continued positive reinforcement
for patients participating in clinical studies through one-on-one contact.
This positive reinforcement, coupled with the relationship the patients
develop with the CTRPhelps improve patient satisfaction and will likely
impart a positive outlook for participation in future studies. Long-term
benefits include improved quality of the data collected, which may
improve the statistical power and quicker approval of the study
medication.

 Data and Safety Monitoring Board

The Data and Safety Monitoring Board (DSMB), also called data monitoring
committee (DMC), is an expert committee, independent of the sponsor,
chartered for one or more clinical trials. The mandate of the DSMB is to
review on a regular basis the accumulating data from the clinical trial to
ensure the continuing safety of current participants and those yet to be
enrolled. The DSMB may review efficacy data at predefined interim points
to assess whether there’s overwhelming evidence of efficacy or the lack
thereof, such that the clinical equipoise at the beginning of the trial is no
longer justified. DSMB has the additional responsibilities to advise the
sponsor regarding the continuing validity and scientific merit of the trial.
Not all clinical trials require a formal DSMB. DSMBs are most common in
double blind randomized phase
3 trials. Members of the DSMB typically include clinical trial experts,
including physicians with the appropriate specialty, at least one
biostatistician and possibly person(s) from other disciplines, such as
biomedical ethics, basic science/pharmacology or law.

 PHARMACOVIGILANCE - SAFETY MONITORING IN CLINICAL TRIALS

Pharmacovigilance is majorly known as drug safety. It is a main integral
part of clinical research. Throughout the product life cycle clinical trials
safety and postmarking pharmacovigilance plays a critical role. The word
pharmacovigilance is derived from two words one is a Greek word which
means "drug" and another “vigilance” is a Latin word which means to
keep awake or to keep watch." Pharmacovigilance is "defined” as the
pharmacological science relating to the detection, understanding,
assessment of adverse effects, particularly long term and short term
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 adverse effects of medicines”. According to WHO Pharmacovigilance (PV)
is the pharmacological science relating to

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 the detection, evaluation, understanding and prevention of adverse effects,
especially long term and short term side effects of medicines.
Aims of Pharmacovigilance
1. To improve patient care & safety

2. To contribute to assessment of benefit, harm & effectiveness of medicine

3. To Identify previously unrecognized adverse effects of the drugs
4. To Promote rational & safe use of medicine
5. To Promote education & clinical training
6. To Identify patient related risk factors of ADR such as dose, age, gender
7. Any response to a drug which is unintended, occurs at particular doses
8. To diagnose or therapy of disease, or the modification, of
physiological characteristics.

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 SCHEDULE Y (DRUG AND COSMETIC ACT 1940,RULES 1945)
REQUIREMENTS AND GUIDELINES FOR PERMISSION TO IMPORT AND /
ORMANUFACTURE OF NEW DRUGS OR TO UNDERTAKE CLINICAL TRIAL

The Drugs and Cosmetics Act, 1940 is an act of the Parliament of India
which regulates the import, manufacture and distribution of drugs in
India. The primary objective of the act is to ensure that the drugs and
cosmetics sold in India are safe, effective and conform to state quality
standards.
Requirements of clinical trial

(1) Approval for clinical trial

(I) Clinical trial on a new drug shall be initiated only after the permission has
been granted by the Licensing Authority under rule 21 (b), and the approval
obtained from the respective ethics committee(s). The Licensing Authority as
defined shall be informed of the approval of the respective institutional
ethics committee(s) as prescribed in Appendix VIII, and the trial initiated at
each respective site only after obtaining such an approval for that site. The
trial site(s) may accept the approval granted to the protocol by the ethics
committee of another trial site or the approval granted by an independent
ethics committee (constituted as per Appendix VIII), provided that the
approving ethics committee(s) is/are willing to accept their responsibilities
for the study at such trial site(s)and the trial site(s) is/are willing to accept
such an arrangement and that the protocol version is same at all trial sites.
(ii) All trial Investigator(s) should possess appropriate qualifications, training
and experience and should have access to such investigational and
treatment facilities as are relevant to the proposed trial protocol. A qualified
physician (or dentist, when appropriate) who is an investigator or a sub-
investigator for the trial, should be responsible for all trial- related medical
(or dental) decisions. Laboratories used for generating data for clinical trials
should be compliant with Good Laboratory Practices. If services of a
laboratory or a facilities outside the country are to be availed, its/their
name(s), address(s) and specific services to be used should be stated in the
protocol to avail Licensing Authority’s permission to send clinical trial related
samples to such laboratory and/or facility(ies). In all cases, information about
laboratory(ies) / facilities to be used for the trial, if other than those at the
investigation site(s), should be furnished to the Licensing Authority prior to
initiation of trial at such site(s).
(iii)Protocol amendments if become necessary before initiation or during the
course of a clinical trial, all such amendments should be notified to the
Licensing Authority in writing along with the approval by the ethics
committee which has granted the approval for the study. No deviations from
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or changes to the protocol should be implemented without prior written
approval of the ethics committee and the Licensing Authority except when it
is necessary to eliminate immediate hazards to the trial Subject(s) or
when change(s)

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involve(s) only logistic or administrative aspects of the trial. All such
exceptions must be immediately notified to the ethics committee swell as to
the Licensing Authority. Administrative and/or logistic changes in the
protocol should be notified tithe Licensing Authority within 30 days.
(2) Responsibilities of Sponsor.-
(i) The clinical trial Sponsor is responsible for implementing and maintaining
quality assurance systems tonsure that the clinical trial is conducted and
data generated, documented and reported in the protocol and Good Clinical
Practice (GCP) Guidelines issued by the Central Drugs Standard Control
Organization, Directorate General of Health Services, Government of India as
well as with all applicable statutory provisions. Standard operating
procedures should be documented to ensure compliance with GCP and
applicable regulations.
(ii) Sponsors are required to submit a status report on the clinical trial to the
Licensing Authority at the prescribed periodicity.
(iii) in case of studies prematurely discontinued for any reason including lack
of commercial interest in pursuing the new drug application, a summary
report should be submitted within 3 months. The summary report should
provide a brief description of the study, the number of patients exposed to
the drug, dose and duration of exposure, details of adverse drug reactions
(Appendix XI), if any, and the reason for discontinuation of the study or non-
pursuit of the new drug application;
(iv) Any unexpected serious adverse event (SAE) (as defined in GCP
Guidelines) occurring during clinical trial should be communicated promptly
(within 14 calendar days) by the Sponsor to the Licensing Authority and to
the other Investigator(s) participating in the study (see Appendix XI).
(3) Responsibilities of the Investigator(s).- The Investigator(s) shall be responsible
for the conduct of the trial according to the protocol and the GCP Guidelines
and also for compliance as per the undertaking given in Appendix VII.
Standard operating procedures are required to be documented by the
investigators for the tasks performed by them. During and following a
subject’s participation in a trial, the investigator should ensure that adequate
medical care’s provided to the participant for any adverse events.
Investigator(s) shall report all serious and unexpected adverse events to the
Sponsor within 24 hours and to the Ethics Committee that accorded approval
to the study protocol within 7 working days of their occurrence.

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Research work:
 The Future Of Clinical Trials: How AI is helping in improvement.

 How Covid-19 has affected clinical trial tech adoption.

Testing new drugs is a slow and expensive process. AI has the potential to
disrupt clinical trials from patient recruitment to adherence monitoring and
data collection and Covid-19 has catalyzed its adoption.

 Why faster clinical trials are critical for pharma companies

Bringing a drug to market is a long and arduous process. Studies

estimate that the clinical trial process — where new drugs are tested on
patients before the FDA approves them — lasts 9 years and costs $1.3B
on average. Clinical trials are conducted in multiple phases, with cost
and complexity increasing from Phase I to Phase III. Up

Despite the time and capital invested in trials, only 1 in 10 drugs that enter
Phase I of a clinical trial will be approved by the FDA.

Clinical trials fail for a variety of reasons, including failure to recruit

enough trial participants, mid-trial patient drop out, side effects, and

inconsistent data. Naturally, trials that fail at a later stage prove more

costly.
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 The current state of clinical trials

After commercially available treatments have failed, patients must

navigate a complicated process to find, enroll, and participate in a clinical
trial. In the infographic below, we map out a typical patient journey.

Furthermore, many clinical studies use rudimentary data collection and

verification methods — which often put the onus on the patient — such as:
sending patient medical records via fax, manually counting leftover pills in
bottles, and relying on patients’ diary entries to determine medication
adherence.

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 How AI could change every stage of clinical trials

Artificial intelligence-powered technology has the potential to change every

stage of the clinical trials process, from finding a trial to enrollment to
medication adherence.

1. Finding a clinical trial

Matching the right trial with the right patient is a time-consuming and
challenging

Patients may occasionally get trial recommendations from their doctors if

the physician is aware of an ongoing trial. Otherwise, the onus of scouring
through ClinicalTrials.gov
— a comprehensive federal database of past and ongoing clinical trials —
often falls on the patient.

 Natural language processing (NLP) can help extract and analyze relevant
information from a patient’s EHR records, compare with eligibility criteria
for ongoing trials, and recommend matching studies.

In fact, extracting information from medical records — including EHRs and lab
images
— is one of the most sought-after applications of artificial intelligence in
healthcare.

However, solutions accessing patient data face a number of challenges,

including unstructured healthcare data and disparate data sources that
don’t communicate with each other.

The EHR interoperability challenge

Despite a $27B federally funded incentive program to encourage hospitals

and providers to adopt EHRs, there is no standard format or centralized
repository of patient medical data.

In fact, it’s still difficult for patients to access their own records from
all the health institutions they’ve visited.

Under the Health Insurance Portability and Accountability Act (HIPAA), data
sharing is allowed with patient consent.

This creates opportunities for AI startups to analyze medical data and

suggest eligible patients within minutes — a process that would otherwise
take months.

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However, issues with securely sharing health information between
institutions and software systems — or interoperability — persist.

The Covid-19 pandemic has underscored this issue and has driven investor
attention to the EHR ecosystem. News mentions for EHRs have also
skyrocketed.

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Different hospitals and providers treating the same patient may not use the
same EHR software to enter data. In many clinical trials, researchers still fax
requests for patient records to hospitals, who often send the data back as
PDFs or images (including pictures of handwritten notes).

This poses a challenge for AI technology. As one study by researchers

from MIT, Harvard, Johns Hopkins, and NYU highlights:

 Startups are approaching the patient recruitment problem from multiple

angles.

Deep 6 AI uses NLP to extract clinical data — such as symptoms, diagnoses,

and treatments — from patient records. Its software can even identify
patients with conditions not explicitly mentioned in EHR data, improving the
match rate between patients and clinical trials. Deep 6 AI was valued at over
$140M in its latest fundraise.

Clinical trial marketplaces, such as the one SubjectWell offers, are another
approach. SubjectWell’s platform allows researchers access pre-screened
patients.

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 to

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A smaller group of companies is attempting to work around interoperability
hurdles with a direct-to-consumer approach. For example, Clara Health
offers a patient-friendly solution to find new treatment options. Its solution
not only matches patients to trials but offers ongoing support throughout the
process, improving retention as well. The company is backed by Founders
Fund and Khosla Ventures.

Established players in other areas of healthcare are also entering the clinical
trials recruitment space. 23andMe is now offering recommendations about
what studies might be a good fit for its 12M+ customers based on their
genetics.

Other emerging consumer-focused recruitment solutions include:

 Disease-specific social networking platforms like Be the Partner

 Open-source frameworks like Google Health Studies, which researchers
can use to create their own apps for conducting research studies

 Acquisitions as a strategy to get patient data

Flatiron Health tackled the interoperability problem by acquiring an

oncology-focused electronic medical record (EMR) company Altos
Solutions in 2014.

At the time, Flatiron was selling its cloud analytics platform to healthcare
and life science companies, and Altos’ EMR was being used by oncology
institutions like Florida Cancer Specialists. The deal gave Flatiron direct
access to raw patient data, instead of relying solely on access to third-party
EMRs.

Roche subsequently acquired Flatiron for $2B+ in 2018 to gain access to its
real-world evidence — insights generated from EHRs, claims, and wearable
sensors. Roche plans to use this data to improve its cancer treatment
pipeline development.

Meanwhile, biopharma companies continue to partner to gain access to

patient data. For example, Janssen Pharmaceuticals partnered with
Tempus in November 2020 to gain access to its clinical and molecular
patient database and improve patient identification.

2. Challenges with enrollment

o Unfortunately, enrollment challenges do not end when a patient

chooses a clinical trial.

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o To confirm eligibility, the patient must complete a preliminary phone
screen and then undergo examination by a participating site in person or
virtually.

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o Every trial includes inclusion and exclusion criteria that each patient
must meet in order to participate. These terms are often riddled with
medical jargon, as can be seen in the below screenshot of eligibility
criteria from a Phase II breast cancer trial.

In the above example, patients must go through evaluations, like laboratory and
imaging tests, to make sure they meet all the inclusion and exclusion criteria.
Depending on their availability and how far they live from a trial site, some patients
may be able to complete these procedures in less than a week. But for others with
children, inflexible jobs, or long commutes, the process could take multiple visits.
 Telehealth services could help streamline
this process. For example, Deaconess
Health System partnered with TytoCare in
2020 to integrate the startup’s connected
exam tools with Deaconess Clinic LIVE, the
health system’s proprietary virtual care
platform.
o Tyto’s device and accompanying
smartphone app allow quarantined patients
to carry out their own exams by capturing
data from the heart, lungs, throat, ears,
skin, and abdomen. They can then share
their results in real time with remote
physicians.

3. Medication adherence

Once patients enroll in a study, they receive the experimental study drug (or
placebo).
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Patients go home with the first course of the medication (for example, a 30-
day pill bottle with instructions on dosage) and a diary to fill out daily.
Many clinical studies still use paper diaries instead of electronic systems.
Patients are asked to note when they took the study drug, what other
medications were taken on those days, and any adverse reactions (including
headache, stomach ache, or muscle aches).

This process is plagued with inefficiencies:

 Reliance on patient memory.

 Outdated recording system.
 Risk of drop out.
 Additional payments..

Non-adherence can have adverse effects on a patient’s health, incur

costs if a study has to recruit new patients, and interfere with the
accuracy of study outcomes.
Generally, adherence rates of 80% or more are required for therapeutic
efficacy. However, up to 50% of medications prescribed in the US are taken
incorrectly. In response, clinical study sponsors are investing in emerging
technology to minimize non- adherence.

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 Visual, auditory, and digital phenotyping for medication adherence assessment

Some startups are providing visual confirmation of medication administration.

Platforms like AiCure use an interactive medical assistant (IMA) to identify
patients at risk of non-adherence based on visual data collection. Patients
use their phones to take a video of themselves swallowing a pill, and AiCure
confirms that the right person took the right pill.
The company raised a $24.5M Series C led by Baird Capital in late 2019 and
partnered with Science 37 in April 2020 to enable virtual clinical trials.

Other emerging technologies include digital phenotyping and speech analytics

for medication adherence assessment.
ARCH Venture Partners-backed mental health startup Mindstrong uses digital
phenotyping technology to measure mood based on how users interact with
their mobile device.
Aural Analytics, which uses speech detection to identify subtle changes in
users’ brain health, recently partnered with Mass General Hospital for an
amyotrophic lateral sclerosis (ALS) trial.

 AI and IoT for remote patient monitoring

To enable remote patient monitoring for clinical trials, some startups are
developing their own monitoring devices and sensors, then adding a layer of
machine learning to interpret the data. Others are only developing the AI
software and integrating with third- party at-home monitoring devices.
 Connected devices can facilitate real-time study medication adherence.
For example, optimize.health (previously Pillsy) launched a smart
medication bottle with

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 a corresponding mobile application that provides reminders,
educational content, dose tracking, and patient-reported data
capabilities for providers. The company, which is now positioned as a
remote patient monitoring platform, raised a $15M Series A in August
2020.
 Other solutions focus on capturing
physiological data. AliveCor’s wearable
electrocardiogram (EKG) device applies
machine learning to real- time data to
detect abnormal heart rhythms, such as
atrial fibrillation (AF). In April 2020, the
company partnered with Medable to
enable decentralized cardiology-focused
clinical trials. AliveCor most recently
raised a $65M Series E round in
November.

 Meanwhile, Sequoia Capital-

backed Biofourmis uses wearable medical
devices to track users’ vitals on its AI
platform and provide predictive insights
into their health.
The startup partnered with the University of
Hong Kong to capture the temperature, heart
rate, and
oxygen levels of patients infected with Covid-19 to detect subtle changes in
health and help accelerate virus research.

 How Covid-19 has affected clinical trial tech adoption

The Covid-19 pandemic has catalyzed the adoption of technologies that
can improve the efficiency and cost of clinical trials.

 Study design

Adaptive design — which involves a more flexible approach to conducting a

trial — has been a key trend as researchers grapple with Covid-19.

While traditional studies can be rigid about key endpoints and dosing
regimens before commencing the next phase, an adaptive design allows
researchers to modify such metrics as trials progress.

Regeneron Pharmaceuticals‘ and Sanofi’s trial evaluating an antibody

treatment for Covid-19 patients followed an adaptive design. The World
Health Organization’s SOLIDARITY trial has also adopted this model by using
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a randomized, non-double- blind model to emphasize speed. (In double-blind
studies, neither the researcher nor the patient knows which treatment the
patient is receiving.)

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 Another trend in Covid-19 study initiatives is the use of open research
forums to expedite potential findings and conclusions.

For example,

1. AI-based clinical trials company Mendel.ai partnered with DCM Ventures to

create a Covid-19 search engine where researchers can pull data to run their
respective studies.

2. Owkin also launched its Covid-19 Open AI Consortium (COAI), which

promotes collaboration in key research areas such as cardiovascular
complications.

As clinical trial designs come under the microscope during this global pandemic,
these initiatives could provide learning opportunities for researchers as
alternative methods to traditional study design practices are challenged.

 Virtual trials

1. The Covid-19-driven adoption of telemedicine and remote monitoring

solutions has spurred interest in virtual or decentralized clinical trials.The
remote model is not compatible with all types of clinical trials, such as those
that require frequent diagnostic imaging or other in-person assessments.
However, this model presents an opportunity to better accommodate
patient participation.

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The potential benefits of virtual trials include reduced costs, a wider network of
eligible patients, and better patient retention rates.

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One company in this space is Science 37, which offers end-to-end clinical
trial services using its virtual Metasite model. It leverages a network of
investigators, mobile nurses, and study coordinators with the aim of making
studies more accessible to patients.

In April 2020, the company announced a partnership with Innovo Research

to decrease the time required to begin a Covid-19 clinical trial. The initiative
plans to do this by leveraging Innovo’s national network of sites and patients
and applying Science
37’splatform. The novel coronavirus has spurred new discussions around how
technology can address key gaps in today’s clinical trial landscape. As
reliance on these technologies grows, future trials could be reshaped by
these software platforms.

(Reference –cbinsights Research paper about FUTURE OF CLINICAL TRIALS)

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Conclusion
Advances in biomedical research have produced significant opportunities to
improve cancer prevention, detection, and treatment. Insights about the
genomic and molecular mechanisms of disease have enabled basic scientists
to identify new therapeutic targets and develop new agents that are
changing the paradigm of cancer research from nonspecific, broadly toxic
chemotherapies to highly targeted combinations of therapies. However, the
ability to translate biomedical discoveries into advances in care for patients
with cancer remains dependent on the clinical trials system. Clinical trials
provide an essential link between scientific discovery and clinical practice.
These trials are crucial to the translation of new knowledge into tangible
benefits for patients, and the knowledge gained in a clinical trial can also
inform and guide further research into the biology of the disease.

 REFERENCES

 Essentials of Medical pharmacology , KDTRIPATHI 7 TH EDITION ,

Jaypee brothers Medical publisher pvt ltd.
 Orphanet journal of rare diseases.
 CDSCO document SCH Y (Drug and cosmetic act,1940 and Rules 1945).
 “ TEXTBOOK OF REGULAYORY AFFAIRS “ peevee publications.
 An article from “Oxford Handbook of clinical and healthcare research”.
 Indian Journal of pharmacology by WOLTER KULVERS –
MedKnow publications.
 European journal of pharmaceutical and medical research-
An article on “PvPI – A study”.
 Cbinsights research paper –“ FUTURE OF CLINICAL TRIALS.

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