Welcome to the Knowledge Center, designed to give you immediate access to timely and relevant information about clinical trials. Here, you will find frequently asked questions, podcasts, a glossary of clinical trial terms, clinical trial articles, and much more – all to keep you informed and aware.
Clinical Trials Frequently Asked Questions
Clinical Trial Glossary
A B C D E F G H I J K L M
N O P Q R S T U V W X Y Z
|2 Oct 2009||Alzheimer's Clinical Studies: Clear Guidance On Recruiting Volunteers||Medical News Today||Best Practices|
|1 Sep 2007||Smart Clinical Research Protocols||Journal of Clinical Research Best Practices||Best Practices|
|1 Dec 2006||Making Informed Consent Work for All||Journal of Clinical Research Best Practices||Best Practices|
|2 Nov 2009||Benefits Of Taking Part In Clinical Trials||MedicalNews Today||Benefits/Risks|
|1 Nov 2009||Blazing New Trials: Participants In Drug Tests Balance Risks With Hopes For Breakthrough||Hartford Courant||Benefits/Risks|
|26 Jul 2009||Are Clinical Trials Safe?||Parade||Benefits/Risks|
|4 Aug 2009||Patient Stories: Narratives from Participants in Cancer Clinical Trials||National Cancer Institute||Benefits/Risks|
|Effect on the Family||National Heart Lung and Blood Institute||Benefits/Risks|
|2 Aug 2009||Lack of Study Volunteers Hobbles Cancer Fight||New York Times||Challenges|
|15 Mar 2009||New Report Examines Obstacles to Non-Commercial Clinical Trials||Medical News Today||Challenges|
|9 Jan 2009||Participants In Clinical Trials Should Be Viewed As Partners In Research||Medical News Today||Challenges|
|18 Jan 2008||Study probes why U.S. blacks wary of medical trials||Will Dunham, Reuters||Challenges|
|23 Sep 2009||Should You Join a Research Study? 9 Tips for Volunteers in Clinical Trials||U.S. News and World Report||Overview|
|4 Jun 2006||Milestones in Clinical Research||Journal of Clinical Research Best Practices|
|Clinical Trials – Information for Participants||National Institute of Mental Health||Overview|
|23 Dec 2009||Overcoming Lupus: 2009: A Year of Many Firsts||Lupus Foundation of America||Disease Specific|
|13 Mar 2009||Billionaire Google Co-Founder To Back Large Parkinson's Study||Catharine Paddock, Ph.D., Medical News Today||Disease Specific|
|1 Jan 2006||Clinical Trial Agreement Trivia||Journal of Clinical Research Best Practices||Regulation|
Clinical trials are conducted by medical personnel, such as doctors and nurses. Doctors who conduct clinical trials are also called investigators. The clinical trial team, or site staff, may also include social workers and other specialized health care professionals.
The investigators will:
Check your general health at the beginning of the trial
Give you specific instructions for participating in the trial
Closely monitor your safety and check your progress throughout the trial
Stay in touch with you after the trial is completed
What happens in a clinical trial depends on the trial itself. However, you will most likely need to visit the trial clinic at some point to receive instructions and have tests or evaluations performed. In some clinical trials, there may be more tests and trial-related visits than you would normally have for a particular illness or medical condition. These additional medical tests and clinic visits help site staff monitor your general health and safety throughout the trial carefully.
- Treatment trials test investigational treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.
- Prevention trials look for better ways to prevent a given disease from occurring in people who have never had the disease or prevent the disease from returning. These approaches may include medicines, vitamins, vaccines, minerals or lifestyle changes.
- Diagnostic trials are conducted to find better medical tests or procedures for diagnosing a particular disease or medical 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 chronic illnesses.
- Interventional: During this type of trial, you are given a specific treatment defined by the protocol, and the results are measured by investigators.The investigators in interventional studies take an active role by administering a drug or a medical device and measuring its effects.
- Observational: In this type of trial, you are not given any specific treatment; but you are observed by the site staff and any changes in your medical condition are closely monitored. The results of this trial are measured by investigators. In observational studies, the investigators take a passive role, only observing associations between volunteers’ current treatments and their health status. No treatments are administered related to the trial.
- Play an active role in your own health care
- Gain access to new medical treatments before they become widely available
- Obtain expert medical care at leading healthcare facilities during the trial
- Help others by contributing to medical research
However, every clinical trial has some risks, including:
- There may be unpleasant, serious or even life-threatening side effects to the investigational treatment
- The investigational treatment may not be effective for you
- The protocol may require more of your time and attention then would a non-protocol treatment, including trips to the clinic, more medical treatments, hospital stays or complex dosage requirements
Any potential risks related to a clinical trial will be fully explained to you before you enroll in the study.
- Phase I Trials – In Phase I trials, researchers test an investigational drug or treatment in a small group of people (20-80) to evaluate its safety, determine a safe dosage range, and identify any side effects. Many times Phase I trials are conducted using only healthy volunteers. Phase I trials are the first time an investigational treatment is tested on humans; however, substantive research with and testing of the investigational medication has already occurred, with favorable results, to get to this stage of the process.
- Phase II Trials – In Phase II trials, the investigational drug or treatment is given to a larger group of people (100-300) with the targeted medical condition to see if it is effective and to further evaluate its safety.
- Phase III Trials – In Phase III trials, the investigational drug or treatment is given to large groups of people (1,000-3,000) with the targeted medical condition to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the investigational treatment to be used safely.
- Phase IV Trials – In Phase IV trials, additional information, including the drug’s risks, benefits, and optimal use, is collected.
Trials can take place in a variety of locations, such as hospitals, universities, doctors’ offices or community clinics.
Also, many participants qualify for multiple trials. However, you normally cannot participate in more than one trial at a time, and there is a minimum waiting period between trials. This waiting period is known as the “wash-out period” and normally varies between one and four months, depending on the medicine that was tested. Also, if you are a blood donor, you will need to meet a minimum wash-out period for blood donation, which will vary from trial to trial.
- Who may participate in the clinical trial
- The schedule of tests, procedures, medications and dosages
- The length of the clinical trial
- How often and when you are to be seen by the site staff so they can monitor your health and determine the safety and effectiveness of your treatment
In many clinical trials, one group of patients will be given an investigational drug while the control group is given either a standard treatment for the illness or a placebo, a substance that looks like the investigational drug but contains no active medication. It is very important that clinical trial participants and site staff do not know which treatment the participant receives. This ensures that any existing opinions about the investigational drug and/or placebo do not affect final trial results.
The investigator, or clinical trial doctor, will provide you with detailed information about the trial to allow you to decide whether or not to participate. The process of understanding the risks and benefits of a trial is known as informed consent. The doctor will continue to keep you informed throughout the trial and will provide you up-to-date information.
The investigator will provide an informed consent document that includes details about the study, such as:
- Purpose of the research
- Trial duration/how long it will last
- Details about the investigational treatment
- Medical tests and procedures required by the trial
- Key trial contacts
- Risks of participation
- Potential benefits of participation
You should know as much as you can about the clinical trial and feel comfortable asking your doctor any questions you may have related to the trial. Once you are comfortable with your understanding of what is involved, you will have the opportunity to decide whether or not to sign the informed consent document, stating that you are willing to participate. However, keep in mind that the informed consent document is not a contract, and you may withdraw from the clinical trial at any time and for any reason.
- Identify appropriate participants
- Protect participants’ safety
- Help ensure that investigators will be able to answer their research questions
Guidelines for participation can be based on:
- For some studies, the type and stage of your disease
- Previous or current treatments and medications
- Other existing medical conditions
Every clinical trial in the United States must be approved and monitored by an Institutional Review Board (IRB) to make sure the risks are as low as possible and are worth any potential benefits. An IRB is an independent committee of physicians, statisticians, community advocates and others that ensures a clinical trial is ethical and the rights of participants are protected. Many countries have similar review boards and regulations.
- Write down any possible questions you might have
- Ask a friend or relative to come along for support and to hear the responses to your questions
- Bring a tape recorder to record the discussion and to replay later
You can also find a list of questions for the study doctor on the Questions to Ask Your Doctor page.
- Professional development: Be on the cutting edge of your therapeutic area of expertise, meet other investigators, exchange ideas, plan future collaborations, and work with investigational medications and processes that are not yet approved by the FDA.
- Professional recognition: Use your role as an investigator to co-author articles for publication and be recognized as a thought leader within the medical community.
- Personal satisfaction: Offer your patients new medical treatments that may only be available through participation in clinical trials
- New revenue stream: Add additional revenue to your medical practice, based on compensation provided by sponsors for your time spent conducting clinical trials.
- Role in the advancement of medicine: Be a leader in your field by potentially bringing breakthrough drugs and medical devices – products that could impact the health of people around the world – to market.
You can learn more about GCP and how to become a certified investigator through the Academy of Pharmaceutical Physicians and Investigators. However, certification is not required to become a clinical trial investigator. The Drug Information Association is also a good resource.
When considering a specific trial, you may want to ask yourself:
- Does this trial fit my patient population?
- Is there an adequate patient population to meet enrollment goals?
- Do I have the necessary equipment to conduct this trial?
- Does my practice have the ability to store investigational products properly?
- Do I have adequate staff to perform the responsibilities of this trial?
- What would be the compensation to me for participating?
- Am I, along with my staff, committed to all that will be involved in this trial?
- Signed statement of investigator (Form FDA 1572)
- Applicable regulations
An investigator is also responsible for:
- Protecting the rights, safety and welfare of all study participants
- Controlling and accounting for the drugs being studied/stored at the study site
- Obtaining the informed consent of each study participant
- Progress reports: The investigator furnishes all reports to the study sponsor or the sponsor’s representative. The results are collected, evaluated and submitted to regulatory agencies.
- Safety reports: An investigator promptly reports (to the sponsor) any adverse effect that may reasonably be regarded as caused by, or probably caused by, the study drug. If the adverse effect is alarming, the investigator must report the adverse effect immediately.
- Final report: An investigator provides the sponsor with an adequate report shortly after completion of the investigator’s participation in the study.
- Financial disclosure reports: The investigator provides the sponsor or the sponsor’s representative with sufficient and accurate financial information to allow the sponsor to submit complete and accurate certification or disclosure statements. The clinical investigator should promptly update this information if any relevant changes occur during the course of the study and for one year following the completion of the study.
An investigator is required to prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the study for each individual trial participant. The case history for each individual shall document that informed consent was obtained prior to participation in the study.
In the United States, an investigator retains records for a period of two years following the date that a marketing application is approved for the drug and for the indication for which it was being investigated. If no application is filed, or if the application is not approved for the indication, the investigator must keep records until two years after the study is discontinued.
- Target Identification. Drugs usually act on either cellular or genetic chemicals in the body, known as targets, which are believed to be associated with disease. Scientists use a variety of techniques to identify and isolate individual targets to learn more about their functions and how they influence disease. Compounds are then identified that have various interactions with the drug targets that might be helpful in treatment of a specific disease.
- Target Prioritization/Validation. To select targets most likely to be useful in the development of new treatments for disease, researchers analyze and compare each drug target to others based on their association with a specific disease and their ability to regulate biological and chemical compounds in the body. Tests are conducted to confirm that interactions with the drug target are associated with a desired change in the behavior of diseased cells. Research scientists can then identify compounds that have an effect on the target selected.
- Lead Identification. A lead compound or substance is one that is believed to have potential to treat disease. Laboratory scientists can compare known substances with new compounds to determine their likelihood of success. Leads are sometimes developed as collections, or libraries, of individual molecules that possess properties needed in a new drug. Testing is then done on each of these molecules to confirm its effect on the drug target.
- Lead Optimization. Lead optimization compares the properties of various lead compounds and provides information to help biopharmaceutical companies select the compound or compounds with the greatest potential to be developed into safe and effective medicines. Often during this same stage of development, lead prioritization studies are conducted in living organisms (in vivo) and in cells in the test tube (in vitro) to compare various lead compounds and how they are metabolized and affect the body.
- Preclinical Technology. During the preclinical development of a drug, laboratory tests document the effect of the investigational drug in living organisms (in vivo) and in cells in the test tube (in vitro).
- Chemistry Manufacturing and Controls (CMC)/Pharmaceutics. The results of preclinical testing are used by experts in pharmaceutical methods to determine how to best formulate the drug for its intended clinical use. For example, a drug that is intended to act on the sinuses may be formulated as a time-release capsule or as a nasal spray. Regulatory agencies require testing that documents the characteristics – chemical composition, purity, quality and potency – of the drug’s active ingredient and of the formulated drug.
- Pharmacology/Toxicology. Pharmacological testing determines effects of the candidate drug on the body. Toxicology studies are conducted to identify potential risks to humans.
Results of all testing must be provided to the FDA in the United States and/or other appropriate regulatory agencies in order to obtain permission to begin clinical testing in humans. Regulatory agencies review the specific tests and documentation that are required to proceed to the next stage of development.
- Investigational New Drug (IND)/Clinical Trial Exception (CTX)/Clinical Trial Authorization (CTA) Applications. INDs (in the United States), CTXs (in the U.K.) and CTAs (in Australia) are examples of requests submitted to appropriate regulatory authorities for permission to conduct investigational research. This research can include testing of a new dosage form or new use of a drug already approved to be marketed.
In addition to obtaining permission from appropriate regulatory authorities, an institutional or independent review board (IRB) or ethical advisory board must approve the protocol for testing as well as the informed consent documents that study volunteers sign prior to taking part in a clinical study. An IRB is an independent committee of physicians, community advocates and others that ensures a clinical trial is ethical and the rights of study volunteers are protected.
Clinical testing is usually described as consisting of Phase I, Phase II and Phase III clinical studies. In each successive phase, increasing numbers of people are tested.
- Phase I Clinical Studies. Phase I studies are designed to verify safety and tolerability of the candidate drug in humans and typically take six to nine months. These are the first studies conducted in humans. A small number of people, usually from 20 to 100 healthy volunteers, take the investigational drug for short periods of time. Testing includes observation and careful documentation of how the drug acts in the body – how it is absorbed, distributed, metabolized and excreted.
- Phase II Clinical Studies. Phase II studies are designed to determine effectiveness and further study the safety of the candidate drug in humans. Depending upon the type of investigational drug and the condition it treats, this phase of development generally takes from six months up to three years. Testing is conducted with up to several hundred people who suffer from the condition the investigational drug is designed to treat. This testing determines safety and effectiveness of the drug in treating the condition and establishes the minimum and maximum effective dose. Most Phase II clinical trials are randomized, or randomly divided into groups, one of which receives the investigational drug, one of which gets a placebo containing no medication and sometimes a third group that receives a current standard treatment to which the new investigational drug will be compared. In addition, most Phase II studies are double-blinded, meaning that neither volunteers nor researchers evaluating the compound know who is receiving the investigational drug or placebo.
- Phase III Clinical Studies. (underlined words are a link to the glossary or have a pop-up explanation) Phase III studies provide expanded testing of effectiveness and safety of an investigational drug, usually in randomized and blinded clinical trials. Depending upon the type of drug candidate and the condition it treats, this phase usually requires one to four years of testing. In Phase III, safety and efficacy testing is conducted with several hundred to thousands of people who suffer from the condition the investigational drug treats.
- New Drug Application (NDA)/Marketing Authorization Application (MAA). NDAs (in the United States) and MAAs (in the U.K.) are examples of applications to market a new drug. Such applications document safety and efficacy of the investigational drug and contain all the information collected during the drug development process. At the conclusion of successful preclinical and clinical testing, this series of documents is submitted to the FDA in the United States or to the applicable regulatory authorities in other countries. The application must present substantial evidence that the drug will have the effect it is represented to have when people use it or under the conditions for which it is prescribed, recommended or suggested in the labeling. Obtaining approval to market a new drug frequently takes between six months and two years.
- Phase IIIb/IV Studies. Phase IIIb trials, which often begin before approval, may supplement or complete earlier trials by providing additional safety data or they may test the approved drug for additional conditions for which it may prove useful. Phase IV studies expand testing of a proven drug to broader patient populations and compare the long-term effectiveness and/or cost of the drug to other marketed drugs available to treat the same condition.
- Post-Approval Studies. Post-approval studies test a marketed drug in new age groups or patient types. Some studies focus on previously unknown side effects or related risk factors. As with all stages of drug development testing, the purpose is to ensure the safety and effectiveness of marketed drugs.
- Information gathered at the beginning of a study from which variations found in the study are measured.
- A known value or quantity with which an unknown is compared when measured or assessed.
- The initial time point in a clinical trial, just before a participant starts to receive the experimental treatment which is being tested. At this reference point, measurable values, such as CD4 count, are recorded. Safety and efficacy of a drug are often determined by monitoring changes from the baseline values.
Source: The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)
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.
- Not yet recruiting: participants are not yet being recruited or enrolled
- Recruiting: participants are currently being recruited and enrolled
- Enrolling by invitation: participants are being (or will be) selected from a predetermined population
- Active, not recruiting: study is ongoing (i.e., patients are being treated or examined), but enrollment has completed
- Completed: the study has concluded normally; participants are no longer being examined or treated (i.e., last patient’s last visit has occurred)
- Suspended: recruiting or enrolling participants has halted prematurely but potentially will resume
- Terminated: recruiting or enrolling participants has halted prematurely and will not resume; participants are no longer being examined or treated
- Withdrawn: study halted prematurely, prior to enrollment of first participant
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Information included in the Glossary is from Clinicaltrials.gov, which uses content from AIDSinfo, CenterWatch, Inc., ECRI, Eli Lilly and Company, MediStudy.com, Inc. and National Cancer Institute.