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					                                      Clinical Trial in Gastroenterology




                                Clinical Trial in Gastroenterology



Biljana Iliev

biljana.iliev@yahoo .com
Home Tel :( 416) 421-7421



Summary:

In health care, clinical trials (Synonyms clinical studies, research protocols and clinical research) are
conducted to allow safety and efficacy data to be collected for new drugs or devices. These trials can only
take place once satisfactory information has been gathered on the quality of the product and its non-
clinical safety, and Health Authority/Ethics Committee approval is granted in the country where the trial
is taking place.

In planning a clinical trial, the sponsor or investigator first identifies the medication or device to be tested.
Usually, one or more pilot experiments are conducted to gain insights for design of the clinical trial to
follow.

Choosing to participate in a clinical trial is an important personal decision. All clinical trials have
guidelines about who can participate. Using inclusion/exclusion criteria is an important principle of
medical research that helps to produce reliable results.

Except for very small trials limited to a single location, the clinical trial design and objectives are written
into a document called a clinical trial protocol. The protocol is the 'operating manual' for the clinical trial,
and ensures that researchers in different locations all perform the trial in the same way on patients with
the same characteristics. (This uniformity is designed to allow the data to be pooled.) A protocol is always
used in multicenter trials.

Currently, most clinical trial programs follow ICH guidelines, aimed at "ensuring that good quality, safe
and effective medicines are developed and registered in the most efficient and cost-effective manner.
These activities are pursued in the interest of the consumer and public health, to prevent unnecessary
duplication of clinical trials in humans and to minimize the use of animal testing without compromising
the regulatory obligations of safety and effectiveness."
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History

Moviegoers in the '30s and '40s were regularly treated to the high drama of a dying patient whose only
hope lay in an experimental drug--usually called a "serum"--that had to be flown through a raging storm,
at night, to the patient's bedside

Beginning in the 1980s, harmonization of clinical trial protocols was shown as feasible across countries of
the European Union. At the same time, coordination between Europe, Japan and the United States led to a
joint regulatory-industry initiative on international harmonization named after 1990 as the International
Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human
Use (ICH).

In 1987, FDA changed its regulations on investigational new drugs (INDs) to specifically authorize
treatment use of such agents. The term "Treatment IND" highlights the fact that an investigational agent
is being administered not primarily to gain information about its safety and effectiveness, as in a
controlled study, but to treat certain seriously ill patients.

As of August 1994, 29 agents had been granted Treatment IND status. At press time, 24 of these drugs
had been approved by FDA and are on the market.

Types

One way of classifying clinical trials is by the way the researchers behave.

         In an observational study, the investigators observe the subjects and measure their outcomes. The
          researchers do not actively manage the experiment. This is also called a natural experiment. An
          example is the Nurses' Health Study.
         In an interventional study, the investigators give the research subjects a particular medicine or
          other intervention. Usually, they compare the treated subjects to subjects who receive no
          treatment or standard treatment. Then the researchers measure how the subjects' health changes.

Another way of classifying trials is by their purpose. The U.S. National Institutes of Health (NIH)
organizes trials into five (5) different types:

         Prevention trials: look for better ways to prevent disease in people who have never had the
          disease or to prevent a disease from returning. These approaches may include medicines,
          vitamins, vaccines, minerals, or lifestyle changes.
         Screening trials: test the best way to detect certain diseases or health conditions.
         Diagnostic trials: conducted to find better tests or procedures for diagnosing a particular disease
          or condition.
         Treatment trials: test experimental treatments, new combinations of drugs, or new approaches to
          surgery or radiation therapy.
         Quality of life trials: explore ways to improve comfort and the quality of life for individuals with
          a chronic illness (a.k.a. Supportive Care trials).
         Compassionate use trials: provide experimental therapeutics prior to final FDA approval to
          patients whose options with other remedies have been unsuccessful. Usually, case by case
          approval must be granted by the FDA for such exceptions.
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Design

A fundamental distinction in evidence-based medicine is between observational studies and randomized
controlled trials. Types of observational studies in epidemiology such as the cohort study and the case-
control study provide less compelling evidence than the randomized controlled trial. In observational
studies, the investigators only observe associations (correlations) between the treatments experienced by
participants and their health status or diseases.

A randomized controlled trial is the study design that can provide the most compelling evidence that the
study treatment causes the expected effect on human health.

Currently, some Phase II and most Phase III drug trials are designed as randomized, double blind, and
placebo-controlled.

Of note, during the last ten years or so it has become a common practice to conduct "active comparator"
studies (also known as "active control" trials). In other words, when a treatment exists that is clearly
better than doing nothing for the subject (i.e. giving them the placebo), the alternate treatment would be a
standard-of-care therapy. The study would compare the 'test' treatment to standard-of-care therapy.

Although the term "clinical trials" is most commonly associated with the large, randomized studies
typical of Phase III, many clinical trials are small. They may be "sponsored" by single physicians or a
small group of physicians, and are designed to test simple questions. In the field of rare diseases
sometimes the number of patients might be the limiting factor for a clinical trial. Other clinical trials
require large numbers of participants (who may be followed over long periods of time), and the trial
sponsor is a private company, a government health agency, or an academic research body such as a
university.

Clinical trial protocol

A Clinical Trial Protocol is a document that describes the objectives, design, methodology, statistical
considerations, and organization of a clinical trial. The protocol gives the background and reason the trial
is being conducted.

It defines a study plan on which the clinical trial is based. The plan is designed to monitor the health of
the participants as well as answer specific research questions. The protocol mainly focuses on the types of
people who may participate in the trial, the schedule of tests, procedures, medications, and the length of
the study. During the clinical trial, study participants are seen regularly by the research team which
usually is consisted of medical doctors and nurses to monitor their health and to determine the safety and
effectiveness of the treatments they are receiving.

The format and content of clinical trial protocols in the United States, Canada and Australia are written to
follow the Good Clinical Practice Guidelines issued by ICH,International Conference on Harmonisation,
an international body that defines standards, which governments can transpose into regulations for clinical
trials involving human subjects.

The existence of a clinical trial protocol allows researchers at different locations to perform the study in
exactly the same way, so that their data can be combined as though they were all working together. The
                                      Clinical Trial in Gastroenterology



protocol also gives the study administrators as well as the local researchers a common reference
document for the researchers' duties and responsibilities during the trial.



Design features

Informed consent

The process of learning the key facts about a clinical trial before deciding whether or not to participate. It
is also a continuing process throughout the study to provide information for participants. To help
someone decide whether or not to participate, the doctors and nurses involved in the trial explain the
details of the study.
Then the research team provides an informed consent document : A document that describes the rights of
the study participants, and includes details about the study, such as its purpose, duration, required
procedures, and key contacts. Risks and potential benefits are explained in the informed consent
document. The participant then decides whether or not to sign the document. Informed consent is not a
contract, and the participant may withdraw from the trial at any time.



Categorize All Studies in Clinical Trials

    Main Category:
        Conditions by Category
        Condition by Disease

Digestive System Diseases:

ConditionAcalculous Cholecystitis,Adenoma, Islet Cell,Alagille Syndrome ,Appendiceal Neoplasms
,Barrett Esophagus ,Bile Duct Neoplasms,Biliary Atresia ,Biliary Tract Diseases,Carcinoma,
Hepatocellular,Carcinoma, Pancreatic Ductal ,Celiac Disease,Cholangitis, Sclerosing Cholecystitis,
AcuteCholedocholithiasis ,Cholestasis,Cholestasis, Intrahepatic,Colitis, Collagenous,Colitis,
LymphocyticColitis, UlcerativeColonic Diseases, FunctionalColorectal Neoplasms,Crohn Disease,Cystic
Fibrosis,Digestive System Abnormalities,…….


Phases

DIFFERENT PHASES OF GASTROENTEROLOGY CLINICAL TRIALS


Gastroenterology involves the diagnosis and treatment of disorders of the digestive system. These
disorders may affect the esophagus, stomach, small intestine, large intestine (colon), rectum, liver,
gallbladder or pancreas. New experimental medications in the gastroenterology field are indicated for
constipation, acid reflux, irritable bowel syndrome (IBS), ulcerative colitis, gastroesophageal reflux
disease (GERD) and Crohn's disease.
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Conditions                                              Prevalence (U.S.)
Constipation                                            4.5 million
Acid reflux                                             60 million
Gastroesophageal reflux disease                         19 million
Irritable bowel syndrome                                15 million
Ulcerative colitis                                      < 1 million
Crohn's disease                                         < 1 million




Pre-clinical Testing

To prove that the compound works as is hypothesized (assumed) and does not produce any negative side
effects, it is first thoroughly tested in animals (i.e., mice, rats, dogs and monkeys). This stage of testing is
commonly referred to as the "pre-clinical" stage. The purpose of these animal studies is to prove that the
drug is not carcinogenic (causes cancer), mutagenic (causes mutations), or teratogenic (causes
malformations), and to understand how the drug is absorbed and excreted. Once a pharmaceutical
company proves that the compound appears to be safe, and possibly effective in animals, the company
will provide this information to the Food and Drug Administration (FDA) in USA or Therapeutic
Products Directorate (TPD) in Canada, requesting approval to begin testing the compound (experimental
drug) in humans via an Investigational New Drug (IND) application.

Clinical Trials/Studies in Humans (Phase 0)

The clinical testing (investigation) of experimental drugs (previously unproven in humans, therefore
"experimental") in humans is normally done in three phases (Phase I, II and III) with more and more
people included in each subsequent phase. Distinctive features of Phase 0 trials include the administration
of single subtherapeutic doses of the study drug to a small number of subjects (10 to 15).Before moving
to the next phase of development the data are carefully analyzed to ensure the experimental drug is at
least safe and well tolerated. After successful completion of Phase I-III testing, a company will submit the
results of all of the studies to the FDA or TPD to obtain a New Drug Approval (NDA). Once the FDA or
TPD grants a company with a NDA, the company can market the drug (medication) to the public.
Additional testing (post-marketing or late phase III/phase IV) to look at the ongoing-term safety
continues. Phase 0 is a recent designation for exploratory, first-in-human trials conducted in accordance
with the U.S. Food and Drug Administration’s (FDA) 2006 Guidance on Exploratory Investigational New
Drug (IND) Studies.[11]


In Phase I clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for
the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

There are different kinds of Phase I trials:

SAD
        Single Ascending Dose studies are those in which small groups of subjects are given a single dose
        of the drug while they are observed and tested for a period of time. If they do not exhibit any
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        adverse side effects, and the pharmacokinetic data is roughly in line with predicted safe values,
        the dose is escalated, and a new group of subjects is then given a higher dose. This is continued
        until pre-calculated pharmacokinetic safety levels are reached, or intolerable side effects start
        showing up (at which point the drug is said to have reached the Maximum tolerated dose (MTD).
MAD
        Multiple Ascending Dose studies are conducted to better understand the pharmacokinetics &
        pharmacodynamics of multiple doses of the drug. In these studies, a group of patients receives
        multiple low doses of the drug, whilst samples (of blood and other fluids) are collected at various
        time points and analyzed to understand how the drug is processed within the body. The dose is
        subsequently escalated for further groups, up to a predetermined level.
Food effect
        A short trial designed to investigate any differences in absorption of the drug by the body, caused
        by eating before the drug is given. These studies are usually run as a crossover study, with
        volunteers being given two identical doses of the drug on different occasions; one while fasted,
        and one after being fed.


In Phase II clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see
if it is effective and to further evaluate its safety.

EXAMPLE FOR II Phase

Tabular View:


Descriptive Information Fields

Brief Title          Combination Chemotherapy Plus Trastuzumab in Treating Patients With Advanced,
                     Recurrent, or Metastatic Colorectal Cancer

Official Title       Phase II Study Evaluating the Combination of 5-Fluorouracil, Leucovorin,
                     Oxaliplatin, and Herceptin in the Treatment of Patients With Metastatic Colorectal
                     Cancer Who Have Progressed After 5-FU and/or Irinotecan-Containing Therapy

Brief Summary        RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells
                     from dividing so they stop growing or die. Monoclonal antibodies such as
                     trastuzumab can locate tumor cells and either kill them or deliver tumor-killing
                     substances to them without harming normal cells.

                     PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy
                     plus trastuzumab in treating patients who have advanced, recurrent, or metastatic
                     colorectal cancer.

Detailed             OBJECTIVES:
Description
                            Determine the response rate of patients who overexpress HER-2/neu with
                             metastatic colorectal adenocarcinoma who have progressed on at least 1
                             prior, but no more than 2 prior, chemotherapy regimens for metastatic
                             colorectal cancer treated with fluorouracil, leucovorin calcium, oxaliplatin,
                             and trastuzumab (Herceptin).
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                         Determine the time to progression of these patients treated with this regimen.
                         Determine the overall toxicity of this regimen in these patients.

               OUTLINE: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days
               1, 8, 15, and 22, followed by oxaliplatin IV over 2 hours on days 1 and 15, and then
               followed by leucovorin calcium IV over 2 hours on days 1, 8, and 15. Fluorouracil IV
               is administered at the midpoint of the leucovorin calcium infusion on days 1, 8, and
               15. Treatment continues every 28 days in the absence of unacceptable toxicity or
               disease progression.

               PROJECTED ACCRUAL: A total of 20-45 patients will be accrued for this study.

Study Phase    Phase II

Study Type     Interventional

Study Design   Treatment

Condition      Colorectal Cancer

Intervention   Drug: fluorouracil
               Drug: leucovorin calcium
               Drug: oxaliplatin
               Drug: trastuzumab

Eligibility    DISEASE CHARACTERISTICS:
Criteria       Histologically confirmed advanced, recurrent, or metastatic colorectal
               adenocarcinoma
               Resected CNS metastases stable greater than 1 month after completion of
               radiotherapy for CNS metastases eligible
               No existing CNS metastases allowed
               Measurable disease
               At least 1 dimension as at least 20 mm with conventional techniques OR
               At least 10 mm with spiral CT scan
               No truly nonmeasurable lesions:
               Bone lesions
               Leptomeningeal disease
               Lymphangitis cutis/pulmonis
               Abdominal masses not confirmed and followed by imaging techniques
               Cystic lesions
               Must have progressed on at least 1 prior, but no more than 2 prior, fluorouracil and/or
               irinotecan containing treatment regimens for metastatic colorectal cancer
               Must have documented HER-2/neu overexpression by immunohistochemistry
               staining
               Staining score at least 2+
               PATIENT CHARACTERISTICS:
               Age:
               18 and over
               Performance status:
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                  ECOG 0-2
                  Life expectancy:
                  Not specified
                  Hematopoietic:
                  Granulocyte count at least 1,500/mm3
                  Platelet count at least 100,000/mm3
                  Hepatic:
                  Bilirubin no greater than 2.0 mg/dL
                  AST no greater than 2.5 times upper limit of normal
                  Renal:
                  Creatinine normal OR
                  Creatinine clearance at least 60 mL/min
                  Cardiovascular:
                  No history of cardiac ischemia or congestive heart failure
                  LVEF at least 50% by ECG or MUGA
                  Other:
                  Not pregnant or nursing
                  Fertile patients must use effective contraception
                  No concurrent second malignancy except nonmelanoma skin cancers or carcinoma in
                  situ of the cervix unless completed therapy and considered to be at less than 30% risk
                  of relapse
                  PRIOR CONCURRENT THERAPY:
                  Biologic therapy:
                  Not specified
                  Chemotherapy:
                  See Disease Characteristics
                  No prior platinum containing chemotherapy
                  At least 3 weeks since prior chemotherapy and recovered
                  No other concurrent chemotherapy
                  Endocrine therapy:
                  Not specified
                  Radiotherapy:
                  At least 3 weeks since prior radiotherapy and recovered
                  Surgery:
                  Not specified

Gender            Both

Ages              18 Years and older

Accepts Healthy   No
Volunteers

Study Sponsor     Cancer and Leukemia Group B

Collaborators     National Cancer Institute (NCI)

Investigators     Hospital
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In Phase III clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to
confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect
information that will allow the drug or treatment to be used safely.




EXAMPLE FOR III Phase




Descriptive Information Fields

Brief Title          Safety of Daily Dose Esomeprazole for GERD for Pediatric and Adolescent Patients

Official Title       A Phase III, Multicentre, Randomized, Double-Blind, Parallel-Group Study to
                     Evaluate the Safety of Once Daily Esomeprazole for the Treatment of Clinically
                     Diagnosed Gastroesophageal Reflux Disease (GERD) in Pediatric and Adolescent
                     Patients 12 to 17 Years of Age, Inclusive.

Brief Summary        This study is a phase III, multi-centre, randomized, double-blind study to assess the
                     safety and tolerability of once daily treatment with esomeprazole 20 or 40 mg in
                     pediatric and adolescent patients 12 to 17 years of age, inclusive, with clinically
                     diagnosed GERD. The treatment period will be up to 8 weeks.

Study Phase          Phase III

Study Type           Interventional

Study Design         Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety
                     Study

Primary Outcome      To evaluate safety & how tolerable a once daily treatment with esomeprazole is in
Measure              pediatric & adolescent patients
                     12 to 17 years of age, inclusive, with clinically diagnosed Gastroesophageal Reflux
                     Disease (GERD)

Secondary            To evaluate the clinical outcome of once daily treatment with esomeprazole in
Outcome              relieving gastroesophageal reflux disease (GERD)-associated signs & symptoms in
Measure              pediatric & adolescent patients 12 to 17 years of age
                     - Assessment of changes from baseline in daily patient symptom assessment as
                     reported by the patient.
                     - Assessment of changes from baseline in Physician Global Assessment.

Condition            Gastroesophageal Reflux Disease (GERD)

Intervention         Drug: Esomeprazole

Enrollment           140
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Eligibility          Inclusion Criteria:
Criteria
                             Provision of signed written informed consent from the patient’s
                              parent/guardian, and assent from the patient prior to conducting of any study-
                              related procedures.
                             Patients must be male or female between the age of 12 and 17 years,
                              inclusive.
                             Patients must have a clinical diagnosis of GERD made by the investigator
                              based on any of the following factors: history, physical examination, review
                              of systems, laboratory test results, or information from diagnostic testing.

                     Exclusion Criteria:
                             Patients who have used a PPI within 14 days prior to randomization,
                              including over-the-counter Prilosec®.
                             Patients who have used any prescription or over-the-counter treatment for
                              symptoms of gastroesophageal reflux disease (GERD), such as Histamine 2
                              Receptor Antagonists (H2RA) or prokinetics, within 3 days prior to
                              randomization. Antacids may be used, except for those containing bismuth.
                             Patients with a known hypersensitivity, allergy, or intolerance to any
                              component of esomeprazole or omeprazole.


Gender               Both

Ages                 12 Years to 17 Years

Accepts Healthy      No
Volunteers

Links to all studies - primarily for crawlers
In Phase IV clinical trials, post marketing studies delineate additional information including the drug's
risks, benefits, and optimal use.

EXAMPLE FOR Phase IV


Descriptive Information Fields

Brief Title        Patient's Perception of Treatment Outcome With Darifenacin by Patients With
                   Overactive Bladder

Official Title     A 12-Week, Open-Label, Non-Randomized, Multicenter Study to Evaluate the
                   Patient's Perception of Outcome After Treatment With Darifenacin in Overactive
                   Bladder (OAB) Patients Dissatisfied With Prior Anticholinergic Therapy

Brief Summary      This study will evaluate safety, efficacy and patient's perception of outcome after
                   treatment with darifenacin (7.5 mg once daily (o.d.) with voluntary increase up to 15
                   mg o.d.) in patients with OAB who are dissatisfied with prior oxybutynin extended
                   release (ER) or tolterodine extended release (ER) therapy.
                                   Clinical Trial in Gastroenterology



Study Phase       Phase IV

Study Type        Interventional

Study Design      Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment,
                  Safety/Efficacy Study

Primary           Change from baseline in the patient's perception of outcome at Week 13 using the
Outcome           Patient Perception Bladder Condition questionnaire (PPBC).
Measure

Secondary         Patient's perception of outcome using the PPBC questionnaire at Week 7.
Outcome           Patient's satisfaction by using the Patient Satisfaction Treatment Benefits questionnaire
Measure           (PSTB, Part I) at Week 13.
                  Assessment of efficacy of darifenacin with respect to change from baseline in:
                  Number of micturitions per day at Weeks 7 and 13
                  Number of urgency episodes per day at Weeks 7 and 13
                  Number of urge urinary incontinence episodes (UUIE) per week at Weeks 7 and 13
                  Assessment of safety and tolerability

Condition         Overactive Bladder (OAB)

Intervention      Drug: Darifenacin

Recruitment Information Fields

Recruitment       Completed
Status

Enrollment

Start Date

Completion
Date

Eligibility       Inclusion Criteria:
Criteria
                         • Symptoms of OAB for at least six months prior to randomization
                              o    ≥ 8 micturitions on average/24 hours
                              o    ≥ 1 urgency episodes on average/24 hours
                              o    with or without UUIE
                                           Patients dissatisfied with prior oxybutynin ER or tolterodine
                                            ER treatment. Patients must have been on either treatment for
                                            at least 1 week and up to 12 months preceding this study. It is
                                            required that either oxybutynin ER or tolterodine ER was the
                                            most recent OAB medication taken.
                                           Patients without prior darifenacin treatment
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                    Exclusion Criteria:

                           • A mean daily urinary volume >3000 mL or a mean volume
                            voided/micturition of >300 mL as verified in the micturition diary for two
                            consecutive days prior to Baseline
                                 o   Males with post-void residual (PVR) urinary volume >200 mL at
                                     Baseline
                                 o   Clinically predominant and bothersome stress urinary incontinence, as
                                     determined by the investigator
                                 o   Urinary retention or clinically significant bladder outlet obstruction as
                                     determined by the investigator

                    Other protocol-defined inclusion / exclusion criteria may apply

Gender              Both

Ages                18 Years and older

Investigators       Study Chair: Pharmaceutical Corporation         PC


Recruitment Information Fields include the desire for same information except information for Eligibility
Criteria are different.


Length

Clinical trials are only a small part of the research that goes into developing a new treatment. Some
reasons a clinical trial might last from 6 months to several years.

Clinical trials that do not involve a new drug usually have a much shorter duration. (Exceptions are
epidemiological studies like the Nurses' Health Study.)

Administration

Clinical trials designed by a local investigator and (in the U.S.) federally funded clinical trials are almost
always administered by the researcher who designed the study and applied for the grant. Small-scale
device studies may be administered by the sponsoring company. Phase III and Phase IV clinical trials of
new drugs are usually administered by a contract research organization (CRO) hired by the sponsoring
company. (The sponsor provides the drug and medical oversight.)

Ethical conduct

Clinical trials are closely supervised by appropriate regulatory authorities. All studies that involve a
medical or therapeutic intervention on patients must be approved by a supervising ethics committee
before permission is granted to run the trial. The local ethics committee has discretion on how it will
supervise noninterventional studies (observational studies or those using already collected data). In the
U.S., this body is called the Institutional Review Board (IRB). Most IRBs are located at the local
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investigator's hospital or institution, but some sponsors allow the use of a central (independent/for profit)
IRB for investigators who work at smaller institutions.

To be ethical, researchers must obtain the full and informed consent of participating human subjects. (One
of the IRB's main functions is ensuring that potential patients are adequately informed about the clinical
trial.)

In some U.S. locations, the local IRB must certify researchers and their staff before they can conduct
clinical trials. They must understand the federal patient privacy (HIPAA) law and good clinical practice.
International Conference of Harmonisation Guidelines for Good Clinical Practice (ICH GCP) is a set of
standards used internationally for the conduct of clinical trials. The guidelines aim to ensure that the
"rights, safety and well being of trial subjects are protected".

Informed consent is clearly a necessary condition for ethical conduct but does not ensure ethical conduct.

Safety

Responsibility for the safety of the subjects in a clinical trial is shared between the sponsor, the local site
investigators (if different from the sponsor), the various IRBs that supervise the study, and (in some cases,
if the study involves a marketable drug or device) the regulatory agency for the country where the drug or
device will be sold.

1. Data and Safety Monitoring Board

2. Safety Monitoring Committee (SMC)

3. Independent Safety Monitor (ISM)

Sponsor

Clinical trials are sponsored or funded by a variety of organizations or individuals such as physicians,
medical institutions, foundations, voluntary groups, and pharmaceutical companies, in addition to federal
agencies such as the National Institutes of Health (NIH), the Department of Defense (DOD), and the
Department of Veteran's Affairs (VA). Trials can take place in a variety of locations, such as hospitals,
universities, doctors' offices, or community clinics. Clinical trials follow a standardized process.

National health agencies such as the U.S. National Institutes of Health offer grants to investigators who
design clinical trials that attempt to answer research questions that interest the agency. In these cases, the
investigator who writes the grant and administers the study acts as the sponsor, and coordinates data
collection from any other sites. These other sites may or may not be paid for participating in the study,
depending on the amount of the grant and the amount of effort expected from them.


IRBs

Approval by an IRB, or ethics board, is necessary before all but the most informal medical research can
begin.
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       In commercial clinical trials, the study protocol is not approved by an IRB before the sponsor
        recruits sites to conduct the trial. However, the study protocol and procedures have been tailored
        to fit generic IRB submission requirements. In this case, and where there is no independent
        sponsor, each local site investigator submits the study protocol, the consent(s), the data collection
        forms, and supporting documentation to the local IRB. Universities and most hospitals have in-
        house IRBs. Other researchers (such as in walk-in clinics) use independent IRBs.
       The IRB scrutinizes the study for both medical safety and protection of the patients involved in
        the study, before it allows the researcher to begin the study. It may require changes in study
        procedures or in the explanations given to the patient. A required yearly "continuing review"
        report from the investigator updates the IRB on the progress of the study and any new safety
        information related to the study.

Regulatory agencies

       If a clinical trial concerns a new regulated drug or medical device (or an existing drug for a new
        purpose), the appropriate regulatory agency for each country where the sponsor wishes to sell the
        drug or device is supposed to review all study data before allowing the drug/device to proceed to
        the next phase, or to be marketed. However, if the sponsor withholds negative data, or
        misrepresents data it has acquired from clinical trials, the regulatory agency may make the wrong
        decision.
       In the U.S., the FDA can audit the files of local site investigators after they have finished
        participating in a study, to see if they were correctly following study procedures. This audit may
        be random, or for cause (because the investigator is suspected of fraudulent data). Avoiding an
        audit is an incentive for investigators to follow study procedures.

Different countries have different regulatory requirements and enforcement abilities. "An estimated 40
percent of all clinical trials now take place in Asia, Eastern Europe, central and south America.

Investigators

Many clinical trials do not involve any money. However, when the sponsor is a private company or a
national health agency, investigators are almost always paid to participate. These amounts can be small,
just covering a partial salary for research assistants and the cost of any supplies (usually the case with
national health agency studies), or be substantial and include 'overhead' that allows the investigator to pay
the research staff during times in between clinical trials.

Patients
Choosing to participate in a clinical trial is an important personal decision. All clinical trials have
guidelines about who can participate.

In Phase I drug trials, participants are paid because they give up their time (sometimes away from their
homes) and are exposed to unknown risks, without the expectation of any benefit. In most other trials,
however, patients are not paid, in order to ensure that their motivation for participating is the hope of
getting better or contributing to medical knowledge, without their judgment being skewed by financial
considerations. However, they are often given small payments for study-related expenses like travel or as
compensation for their time in providing follow-up information about their health after they are
discharged from medical care.
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References:

   1. www.fda.gov
   2. www.jnci.oxfordjournals.org
   3. www.ccnap.org.uk
   4. www.ama-assn.org
   5. www.ncbi.nlm.gov
   6. www.sahealthinfo.org
   7. www.actmagazine.findpharma.com
   8. www.nci.nih.gov
   9. www.pediatrics.aapublications.org
   10. www.ku.edu
   11. www.cancer.gov
   12. www.deathrefrence.com
   13. www.clinicaltrials.gov

				
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