Clinical trials
RajaSekhar Red Poonuru
[Link] (Ph.D)
Glossary
Clinical Trial: A way to test new medications Phases: Stages Placebo: Dummy tablet Protocol: A written plan for the clinical trial
Study sample: People to be studied in the clinical trial
Volunteers: People willing to join the trial
What is a clinical trial
Definition: A clinical trial is a prospective study comparing the effects and value of intervention(s) against a control in humanbeings.
Clinical Research/Trial in general
Any experiment or study in which one or more human subjects receive(s) a drug, biologic, device or procedure for the purpose of determining its potential
beneficial effects, and/or safety and efficacy for diagnostic, therapeutic, or preventative use.
How is a Clinical Trial done?
Identify a health question.
Develop a plan.
Enroll volunteers and follow the plan.
Study the information collected.
Share the results with others.
Improve treatment.
Why is a clinical trial for
Clinical trials are the fastest and safest way to find treatments that work in people and ways to improve health. Interventional trials determine whether experimental treatments or new ways of using known therapies are safe and effective under controlled environments.
Observational trials address health issues in large groups of people or populations in natural settings.
Who can participate in clinical trials
All clinical trials have guidelines about who can participate.
Inclusion/exclusion criteria is principle behind reliable results.
The factors that allow someone to participate in a clinical trial called "inclusion criteria" and those that disallow someone from participating are called "exclusion criteria". These criteria are based on such factors as age, gender, type and stage of a disease, previous treatment history, and other medical conditions. It is important to NOTE that inclusion and exclusion criteria are not used to reject people personally.
Who Can Participate?
Why participate in a clinical trial?
Participants in clinical trials can play a more active role in their own health care, gain access to new research treatments before they are widely available, and help others by contributing to medical research.
What happens during a clinical trial?
Clinical trial team include doctors , nurses, social workers and other health care professionals who check the health of the participant at the beginning of the trial, give specific instructions for participating in the trial, monitor the participant carefully during the trial, and stay in touch after the trial is completed.
Clinical trial participation is most successful when the PROTOCOL is carefully followed and there is frequent contact with the research staff.
What is informed consent?
Informed consent is the process of learning the key facts about a clinical trial before deciding whether or not to participate.
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 that includes details about the study, such as its purpose, duration, required procedures, and key contacts. 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.
What should people consider before participating in a 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?
What are the benefits and risks of participating in a clinical trial
????????
Well-designed and Well-executed Clinical trials are the best approach for eligible participants to: Play an active role in their own health care. Gain access to new research treatments before they are widely available. Obtain expert medical care at leading health care facilities during the trial. Help others by contributing to medical research. Risks There may be unpleasant, serious or even life-threatening side effects. The experimental treatment may not be effective for the participant. The protocol may require more of their time and attention including trips to the study site, more treatments, hospital stays or complex dosage requirements.
What kind of preparation should a potential participant make for the meeting with the research coordinator or doctor?
Plan ahead and write down possible questions to ask.
Ask a friend or relative to come along for support and to hear the responses to the questions. Bring a tape recorder to record the discussion to replay later.
What is an Institutional Review Board (IRB)?
An IRB is an independent committee of physicians, statisticians, community advocates, and others that ensures that a clinical trial is ethical and the rights of study participants are protected.
Every clinical trial must be approved and monitored by an Institutional Review Board (IRB) to make sure the risks are as low as possible and check the worth of any potential benefits.
Where do the ideas for trials come from
From researchers.
After researchers test new therapies or procedures in the laboratory and in animal studies, the experimental treatments with the most promising laboratory results are moved into clinical trials. During a trial, more and more information is gained about an experimental treatment, its risks and how well it may or may not work.
Who sponsors clinical trials?
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, doctor's offices, or community clinics.
Clinical Research Partnerships
Rx Sponsors Regulatory Approval Publications Enhanced Healthcare Sales & Profits CROs/Monitors Fee for Service Expand research capability Work satisfaction
BENEFITS
Investigators Fee for Service Expand research capability Academic interest/recognition Publications Training & special services Patient care alternatives Patients Improved care Decreased expenses New therapies Contribute to science
What are the different types of clinical trials?
Treatment trials test experimental treatments, new combinations of drugs, or new approaches to surgery or radiation therapy. 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. Diagnostic trials are conducted to find better tests or procedures for diagnosing a particular disease or condition. Screening trials test the best way to detect certain diseases or health conditions. Quality of Life trials (or Supportive Care trials) explore ways to improve comfort and the quality of life for individuals with a chronic illness.
What are the phases of clinical trials?
(collecting information)
In Phase I trials, researchers test an experimental drug in a small group of people (20-80) for the first time to pharmacologic actions of drugs, determine the metabolism, evaluate its safety, a safe dosage range, identify side effects.
Phase II trials
In Phase II trials, the experimental 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..
and to determine the common short-term side effects and risks
Phase III trials
In Phase III trials, the experimental 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 experimental drug or treatment to be used safely. provide and adequate basis for physician labeling.
Phase IV trials
In Phase IV trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use
Clinical Trial Phases
PHASE I PHASE II PHASE III Question What are the longterm results in lots of people? Riskiest-First trials in Moderate risk Lowest risk More humans. Performed in Some safety information about information about the safety and volunteers. Used to drug is known. effectiveness is determine doses. known. Shortest A few Medium Length Longest May last weeks to a few Usually about a year. for two to three years. months. Few participants About one hundred At least several participants hundred participants. Is the treatment safe? Does the treatment work?
Risk
Length
Number of participants
Phases of Clinical Trials
Phase I: Safety (1530 people)
A
A A
A A
Phase II: Safety and Effectiveness (Fewer than 100 people)
A A
Phase III: Effectiveness compared to standard of care; Safety (More than 100 to a few thousand)
A
A A
A A
A A
A A
A A
A A
Drug Discovery
Synthesis, Development & Screening (2 10 Years)
NDA Filing FDA Approval
5,000 10,000
compounds screened
Pre-Clinical Testing
Laboratory and Animal Testing (Animal Safety/Efficacy, Bioavailability, Pharmacokinetics, Toxicology)
250
enter pre-clinical testing
Phase I
20 80 healthy volunteers: Determine safety and dosage
5
enter clinical testing
Phase II
100 300 patient volunteers: Assess efficacy and side effects
Phase III
1,000 5,000 patient volunteers: Monitor efficacy and adverse reactions to long-term use
FDA Review & Approval
File IND
1 approved by the FDA Phase IV & V
$800M
Years 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Post-marketing studies and product surveillance
15
Source: PhRMA
26
PRTM 2005
Research Protocol
Who
How
What
Protocol
Why Where When
What is a control group?
A control is the standard by which experimental observations are evaluated. The control group is given either a standard treatment for the illness or a placebo.
What is a HYPOTHESIS?
A Supposition or Assumption advanced as a basis for reasoning or argument, or as a guide to experimental investigation.
Control Group
Randomisation
A
A A
B
B
Investigational Group
Randomization
Advantages Eliminate selection bias Averages out potential bias due to unknown factors Groups are alike on average Guarantees that statistical tests will have valid [Link] levels Make causal statements
Conclusion
Though plenty of molecules discovered everyday proper and systematic and chronological (time based ) study is required for the approval of the drug moieties through the process of preclinical trials in animal based models followed by clinical trials in human volunteers for the release of foolproof drugs and safer molecules for Prophylactic, Diagnostic" and Therapeutic purposes.
Scope of clinical trials (future prospects)
As high as sky and as deep as sea
Ultimate goal
Protecting the mankind
References
[Link] HP, Dale MM, Ritter JM, Moore PK (2003). Pharmacology 5 ed. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4 [Link] R, (1999). Cancer Clinical Trials: Experimental Treatments and How They Can Help You., Sebastopol: O'Reilly & Associates. ISBN 1-56592-566-1 [Link] S-C and Liu JP (2004). Design and Analysis of Clinical Trials : Concepts and Methodologies, ISBN 0-471-24985-8 [Link] SJ (2004), Clinical Trials: A Practical Approach, John Wiley & Sons, ISBN 0-471-90155-5
Rewards
at the top
Yeah!!
Acknowledgements
Thank you
