About Clinical Trials

A Clinical Trial is a research study that uses human subjects to evaluate the effect of interventions or exposures on biomedical or health-related outcomes. There are two types of clinical studies, interventional studies (or clinical trials) and observational studies. ^[1] This could be a treatment that:

• is already used to treat something else
• might have been modified for a new use
• is innovative and just has not been tested on humans yet

While there are advantages to considering participation in clinical trials for treatment, it is important to do everything you can to be aware of dangers and benefits for treatment before participating in a medical trial. There are different phases of clinical trials. Each phase or step for the approval of a drug or treatment is carefully monitored. The different phases of a trial, including testing, follow up with doctors running a trial between treatments and dose changes, is to help determine the effectiveness and possible side effects of each treatment.

In the United States, the Food and Drug Administration (FDA) monitors Clinical Trials to help prevent serious risks to individuals participating. During later phases of clinical trials, the risks of complications may go down. Trials and treatments already successfully used to treat other conditions also help minimize the chances of potential risks or serious complications. With the knowledge of fewer long-term side effects, doctors would know what to look for as possible complications if and when they arise. Every clinical trial in the U.S. 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. ^[2]

1. Informed Consent

Informed Consent is a procedure in which researchers communicate with possible and enrolled partakers about a clinical study. Informed Consent is when researchers explain the following:

• offer all the important material about the study, so that potential participants can elect to enroll (or if already enrolled, to elect to continue participating);
• make sure that potential participants comprehend the risks and possible benefits of participating in the study, and the other choices to the research being conducted;
• emphasize that participating in (and staying in) a clinical study is completely voluntary. Due to the fact that giving consent to join a trial in research does not reach the level of a contract, participants can leave a trial at any time.

The aim of the informed consent procedure is to safeguard participants. It begins when a possible participant first asks for material about a trial and lasts throughout the study until the study ends. The study researcher and possible participant have consultations that include answering the participant's questions about the research study. In addition, all of the significant material about the trial must also be given to the possible participant. It must be a written document that is clear and easy to comprehend. This informed consent document is reread and approved by the human subjects review board for a study trial before it is given to possible enrollees. Usually, a subject must sign an informed consent document to participate in a clinical study.

2. Phases of Clinical Trials^{[3] [4]}

For a treatment to become a drug on the market, it must first go through 3 or 4 clinical trial phases. The early phases are done to make sure the treatment is safe. Future phases try to show if it works better than the standard treatment. You do not have to participate in all phases.

Phase	Purpose	Number of People
Phase 0	Acute Studies: Short Term Effects, 24 Hours Repeated Dose Studies (Subacute Studies): Longer Term Effects, 90 Days Genetic Toxicity Studies: DNA Damage Reproductive Toxicity Studies: Effects on Fertility, Embryonic and Postnatal Development Carcinogenicity Studies: Long Term Effects, 18 to 24 Months Toxic Kinetic Studies: Effects of Toxic Doses to Estimate the Clinical Margin of Safety (There are FDA Rules on Animal Safety)	0 people; variety of animals instead
Phase 1	To find a safe dose To decide how the new treatment should be given, pill form, IV, IM To see how the new treatment affects the human body To determine if the new treatment has an effect on a certain cancer To see how the new treatment affects the human body To compare the new treatment (or new use of a treatment) with the current standard treatment To further assess the long-term safety and effectiveness of a new treatment	15-30 people
Phase 2	To determine if the new treatment has an effect on a certain cancer To see how the new treatment affects the human body	Less than 100 people
Phase 3	To compare the new treatment (or new use of a treatment) with the current standard treatment	From 100 to several thousand people
Phase 4	To further assess the long-term safety and effectiveness of a new treatment	Several hundred to several thousand




3. Pros - Advantages and Benefits of Trial Participation^[5]

• Access to a Promising New Treatments: Participation gives you the ability to receive promising new treatments not available outside of a clinical trial.
• Possibly Better Than Current Choices: Chance of fewer side effects and better results than current treatments.
• First to Benefit from Promising Treatment: When you have a condition that can't be treated by any other method, this offers some possibility to be the first to benefit from an innovative treatment.
• Help Others: Participation means you would be helping others with the same condition.
• Free Treatment: Cost of treatments in a clinical trial is free, and also gives participants free follow-up care you might have needed even if you weren't in a trial.



4. Cons - Disadvantages, and Dangers of Trial Participation^[6]

• Out of Pocket Cost: Trials often mean a lot more time traveling to medical facilities for follow-up tests and treatment.
• Placebo: You may not know if you are receiving the experimental treatment, a previously approved treatment, or a placebo.
• Unexpected Side Effects: There could either be unexpected short or long term side effects to the treatment, including death. No clinical trial is 100% safe.
• May Not Work: New doesn't always mean better. The treatment could be completely ineffective and taken away time to receive a treatment that would have worked just as well or better.
  Notes - For conditions that involve tumors, medications to manage a tumor need to be stopped one month or longer before surgery would be possible. This can result in devastating consequences.



5. Questions to Ask the Researchers^[7]

Anyone interested in participating in an NF2 clinical study or another study should know as much as possible about the trial and feel comfortable asking the research team questions about the study, the related procedures, and any expenses. Some of the following questions might be helpful during a discussion with a research team. Answers to some of these questions are probably provided in the informed consent document.^[8] An informed consent document is a legal document, signed by the patient who explains the treatment, the risks, benefits, and possible alternatives. It is the process by which patients agree to treatment. Many of these questions are specific to clinical trials, but some also apply to observational studies, such as the study being run at the NIH looking at the natural history of tumor growth over a five (5) year period.

• What is being investigated?
• Why do researchers believe the intermediation being tested might be effective? Why might it not be effective? Has it ever been tested before?
• What are the possible interventions that I might get during the study?
• How will it be determined which interventions I receive (for example, by chance)?
• Who will know which intervention I get during the study trial? Will I know? Will all members of the research team know?
• How do the conceivable risks, side effects, and benefits of this trial compare with those of my current treatment?
• What will be expected of me; what will I have to do?
• What tests are involved?
• How frequently will I have to go to the hospital or clinic?
• Will hospitalization be necessary?
• How long will the trial last?
• Who will pay for my involvement?
• Will I be reimbursed for other expenditures?
• What kinds of long-term follow-up is included in the trial?
• If I benefit from the intervention, will I be permitted to continue receiving it after the trial ends?
• Will I get to see the results of the study?
• Who will manage my medical care while I am in the trial?
• What are my alternatives if I am injured during the study?



6. Glossary of Terms^[9]

1. Clinical Trial: a research study that uses human subjects to evaluate the effect of interventions or exposures on biomedical or health-related outcomes. There are two types of clinical studies, interventional studies (or clinical trials) and observational studies.
2. Data: The material collected by investigators during an investigation that will help to understand the study topic.
3. Dose-escalating: A dose-escalating investigation is done with new medicines to help understand how much medicine should be given to an individual. Dose-escalating means slowly increasing the quantity of medicine until the correct amount is determined.
4. Double-blind or Blinded: A blinded investigation is designed so that the human subjects do not know which treatment arm they are on; the doctor knows. A double-blind study is one designed so neither the physician nor the participant knows which treatment arm the individual is taking during the study.
5. Exclusion Criteria: Factors that will prevent a human subject from participating in a specific investigation. Factors can include such things as a subject's safety or to make it easier to understand the study outcomes. Examples of such factors include someone liver problems, or if that subject has already used a drug that is being studied.
6. Inclusion Criteria: Requirements that a subject must meet to be included in a specific study. Examples include T-cell count, viral load, age, weight or other laboratory values.
7. IM Treatment: Integrative Medicine. Alternative Treatments.
8. Informed Consent: A legal document, signed by the patient that explains the treatment, the risks, benefits, and possible alternatives. It is the process by which patients agree to treatment.
9. Observational study: A study that observes study participants and collects information about their medical history, but does not dispense treatments or interfere with their health care.
10. Open-label: An investigational study in which the subjects know which treatment arms and medicines they are on.
11. Placebo: A substitute sugar pill that looks like the drug being studied, but does not contain active medicine.
12. Placebo-controlled: An investigation that provides some subjects with a placebo and some subjects with the medicine so that the effect of the medicine can be compared statistically to no treatment.
13. Power: The number of patients enrolled in a study has a large bearing on the ability of the study to reliably detect the size of the effect of the study intervention. This is described as the "power" of the trial. The larger the sample size or a number of participants in the trial, the greater the statistical power.
14. Protocol: A scientific proposal that describes the purpose for doing a study, how it will be done and the goals of the study.
15. Randomized: This refers to the way people are assigned to different arms of a study. Like tossing a coin, subjects are assigned randomly or by chance to a study arm.
16. Study Arm: An arm of an investigation is a detailed treatment being studied and comprises a group of people usually being compared to another group, or arm, of the study.
17. Treatment-experienced: A term that describes a subject who has already taken at least one antiretroviral medication to treat his or her HIV disease.
18. Treatment-naive: A term that describes a subject who has never taken antiretroviral medications to treat his or her HIV disease.



7. Reference Sources

1. Last Reviewed (August 2012). U.S. National Institutes of Health [ClinicalTrials.gov]. Glossary of Common Site Terms. Web Site: http://clinicaltrials.gov/ct2/about-studies/glossary
2. Last Reviewed: (April 21, 2008). U.S. National Library of Medicine. FAQ: ClinicalTrials.gov - What Protections Are There?. Web Site: http://www.nlm.nih.gov/services/ctprotection.html.
3. Last Reviewed (2008). U.S. National Library of Medicine. ClinicalTrials.gov - Clinical Trial Phases. Web Site: http://www.nlm.nih.gov/services/ctphases.html.
4. Posted (September 01, 2011). National Cancer Institute, U.S. Department of Health and Human Services, National Institutes of Health. Clinical Trials Take Place in Phases. Web Site: http://www.cancer.gov/clinicaltrials/learningabout/Taking-Part-in-Cancer-Treatment-Research-Studies/page3.
5. Last reviewed (February2013). National Cancer Institute, U.S. Department of Health and Human Services, National Institutes of Health. Cancer Clinical Trials. Number 12. Web Site: http://www.cancer.gov/cancertopics/factsheet/clinicaltrials/clinical-trials.
6. Last reviewed (February2013). National Cancer Institute, U.S. Department of Health and Human Services, National Institutes of Health. Cancer Clinical Trials. Numbers 1, 2, 4, 7, 9, 15. Web Site: http://www.cancer.gov/cancertopics/factsheet/clinicaltrials/clinical-trials.
7. Retrieved (2013). U.S. National Institutes of Health [ClinicalTrials.gov]. Considerations. Web Site: http://clinicaltrials.gov/ct2/info/understand#Considerations.
8. Retrieved (2013). U.S. National Institutes of Health [ClinicalTrials.gov]. Informed Consent Form. Web Site: http://clinicaltrials.gov/ct2/help/glossary/informed-consent.
9. Retrieved (November 23, 2013). The Ohio State University Wexner Medical Center. Clinical Trial Glossary. Web Site: http://medicalcenter.osu.edu/research/clinicaltrials/glossary/Pages/index.aspx.