Clinical Trials- An Overview
What is an IRB?
What is Informed Consent?
What are the phases of a Clinical Trail?
Glossary of Clinical Trial terms
CLINICAL TRIALS — AN OVERVIEW
Clinical trials are the most reliable research studies available for proving whether new drugs, devices, or surgical procedures are beneficial in the treatment and prevention of human illness.
For the results to be widely applicable, clinical trials need to include a broad range of people — men, women, and children of different races and ethnicities.
Clinical trials typically compare a new drug, device, or surgical procedure against usual care (the best treatment currently available). They have an important impact on clinical practice as well as the health of the general public regarding the treatment and prevention of human illness. Participants in clinical trials may be randomly assigned or randomized, (meaning assigned by chance, or luck of the draw) to a treatment strategy. They receive either the new treatment under study or usual care. Because neither the patient nor the researcher knows which group offers the better treatment until the trial has concluded, randomization provides the most powerful test as to which strategy is ultimately the most beneficial to humans.
Clinical trials have helped medicine make great strides in treating and preventing human illness. As more knowledge accumulates, the quantity and quality of treatment and prevention strategies available to all of us will continue to improve.
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WHAT IS AN IRB?
An Institutional Review Board is a committee of people appointed to function as a watchdog over participants in clinical trials. The Food and Drug Administration (FDA), requires that these committees periodically review all research. IRBs try to assure that patients enrolled in a trial are protected. No patients can be enrolled in a trial without the prior approval of the IRB. Many hospitals appoint their own IRBs, but smaller institutions, such as ours, that do not have their own IRB, often use an independent IRB who serves the same purpose.
What is the basic objective of IRBs? IRBs are comprised of medical professionals as well as nonmedical professionals and laypersons that review all research with the basic objective to protect trial participants. Specifically, they try to uphold three principles, respect for persons, beneficence, and justice.
Respect for persons requires them to assure that patients are provided with all of the information they need in order to decide if they should enroll.
Beneficence requires them to protect the patients from harm, and maximize the potential benefit.
Justice requires that participants not assigned at random to the new drug, device, or procedure be offered usual medical care of proven benefit.
Why are they qualified to do it? The FDA requires that the IRB should be diverse in terms of gender, ethnicity, and professional experience. An IRB must be composed of a minimum of five members. Many are health professionals — physicians, nurses, pharmacists, and other scientists. They must have at least one non-science committee member, and it is common to see legal professionals and clergy members on an IRB. Also, there must be at least one member not affiliated with the institution either directly or through family ties.
Additionally, no one who may directly benefit financially from the approval of a new therapy may be a voting member of an IRB. In other words, employees of any sponsoring company cannot participate in IRB decisions concerning a particular trial. Further, investigators conducting a trial likewise cannot participate in IRB decisions concerning that trial.
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Before you enroll in a clinical study, the physician — principal investigator, or his/her representative — responsible for your care while on the study must execute what is known as informed consent. This is the information that must be provided to the patient detailing all study obligations, procedures, and potential risks/benefits, as they are known.
The language must be understandable and may not be exculpatory, meaning that you will not waive your legal rights, and the physician, the investigating institution, and the sponsoring company are not released from liability or negligence.
The physician or study coordinator will review the informed consent document in detail with you. This document is required under federal law to include information pertaining to the following:
A statement that the study involves research including the purpose of the research, the duration of your involvement, and the procedures that will be completed.
A description of any known risks or foreseeable discomforts to the patient.
A description of any expected benefits to the patient or to others as a result of participation in the trial.
A disclosure of appropriate alternative treatments or procedures that might be beneficial to the patient.
An explanation of whom to contact with any questions or concerns pertaining to the research, your rights as a research subject, and to report any events you feel may be related to the research.
A statement that participation is voluntary, and that you may discontinue participation at any time without penalty.
A statement regarding confidentiality, explaining that your identity will be guarded, but that blinded medical records will be available to the Food and Drug Administration for their review.
Should the research involve more than minimal risk, a statement explaining what compensation or treatment will be available to you should injury occur during the trial, and where you may obtain further information concerning compensation and treatment.
The above information has been reviewed by an Institutional Review Board (IRB) prior to the enrollment of any patients. The purpose of the IRB is the review, approval, and continuing review of all clinical investigations. Specifically, the goal of this continual review is the protection of the study subjects.
Before the facility conducting the study is able to enroll any patients, these documents must be carefully prepared, reviewed, and approved; all specific to each individual clinical trial. The physician, or their representative is required to review this with you, and you are encouraged to clarify any questions or concerns you have at this time. This is not a contractual agreement, and you may still decide to withdraw from the study at your discretion. This is simply a statement, which demonstrates that the details of the study were disclosed to you, and that you elected to participate. If you decide to participate and sign the consent form, you should receive a copy of the consent with all the appropriate signatures, such as your signature, the person who performed the consent discussion with you and the investigator who is running the trial.
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THE FOUR PHASES OF CLINICAL TRIALS
Phase I trials are the first step in testing a new treatment in humans and are primarily concerned with assessing safety by monitoring for any harmful side effects. In these trials, researchers look for the best way to administer a treatment; such as whether by mouth (orally), by injection into the blood (intravenously), by injection into the muscle (intramuscularly), and also look at the frequency at which a treatment should be administered (e.g., how many times a day, etc.). Phase I trials typically require a relatively small number of participants.
Phase II trials continue safety monitoring, as for example, dosage levels are increased to determine the optimal benefit to risk range (the range of doses at which humans receive optimal benefits with minimal risk). As in Phase I, these trials also typically require a relatively small number of participants.
Phase III trials typically compare the outcome of participants randomized to the new treatment (the Intervention Group) with those assigned to the best available standard drug, device, or surgical procedure (Comparison or Control Group).
Many Phase III trials utilize a placebo, an inactive or inert substance that appears identical to the product under investigation. The use of the placebo allows for an unbiased assessment of side effects from the new treatment.
Many Phase III trials use a double-blind design, meaning that neither the participant nor the researcher knows who is getting the new intervention and who is getting usual care. However, if some extreme effect emerges (either beneficial or harmful) the external Data and Safety Monitoring Board (DSMB), which oversees the clinical trial, can recommend either its early termination or alteration of the design.
Phase III trials typically enroll large numbers of participants, ranging from hundreds to tens of thousands of people. They may be conducted simultaneously at many sites across the United States as well as in other countries, at facilities including major medical centers, community hospitals and clinics, doctors' offices and veterans' and military hospitals.
At the end of the Phase III trial, researchers analyze the data to assess the benefits of the new treatment, inform the participants, and publish their findings in peer reviewed medical journals for the medical community as well as the general public. If the new treatment is beneficial, the clinical trial results are submitted to the US Food and Drug Administration (FDA), which considers whether to grant approval for its use.
Phase IV trials are conducted after the FDA has granted approval to monitor long term effectiveness of a treatment and its impact on quality of life, as well as to compare its cost effectiveness relative to other treatments.
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GLOSSARY OF CLINICAL TRIALS TERMINOLOGY
Clinical Trial: The most rigorous method for evaluating the safety and efficacy of a new drug, device, or surgical procedure on a group of individuals who are willing to participate and meet the eligibility requirements to be randomized. (See Randomization, below.)
Clinical Research Associate (CRA): A representative of either the sponsor or contract research organization (CRO) that is responsible for monitoring the quality of the conduct of the clinical trial.
Contract Research Organization (CRO): A company funded by the sponsor to manage the day-to-day aspects of the clinical trial.
Control (Comparison) Group: The group of participants in a clinical trial who have been randomly assigned to the treatment group receiving the usual standard of care. (See Standard of Care, below).
Data and Safety Monitoring Board (DSMB): An external, independent, multi-disciplinary group of experts who monitor a clinical trial's progress as well as accumulating data for the emergence of any early benefit or harm. The DSMB usually recommends continuation, but may recommend alteration or early termination in which case there is immediate reporting of findings.
Food and Drug Administration (FDA): The US government regulatory agency responsible for monitoring and enforcing policies that regulate the manufacturing, testing, and marketing of the drugs and devices. The FDA must approve all drugs and devices prior to their commercial availability.
Informed Consent: A process by which the researcher explains all potential risks and benefits of a clinical trial to potentially willing and eligible participants. The Institutional Review Board (IRB) must approve the informed consent and all potential participants must sign the form in advance of starting the clinical trial.
Institutional Review Board (IRB): IRBs are composed of medical professionals as well as non-medical professionals and lay persons who review all research to protect participants. Specifically, they try to uphold three principles, namely respect for persons, beneficence and justice.
Placebo: An inactive or inert substance, which is identical in appearance to the product under investigation.
Principal Investigator: The medical researcher who has the overall authority and responsibility for the clinical trial.
Protocol: The outline for the clinical trial, which includes the specific objectives, the eligibility criteria, and the procedures to be completed. An IRB must approve the protocol before a participant can be randomized into the clinical trial.
Randomization: The method of assigning patients by chance (luck of the draw) to either the treatment under investigation or to the existing standard of care. This is the only reliable means of verifying the small to moderate benefits of new treatments.
Sponsor: The pharmaceutical, research, or health organization that funds the clinical trial.
Standard of Care: The current best available drug, device, or surgical procedure in medical practice.
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