1. Clinical Trials and You Ellen Valentine, M.S., CCC-SLP Community Outreach and Education Program Science Park Research Division, Smithville, Texas

2. What Are Clinical Trials? A type of research study carried out on people. Designed to learn about a potential new treatment, devices or other medical procedures and their effects. They follow strict government guidelines to protect participants and provide solid proof of the effectiveness of a new medical procedure or drug.

3. What Is The Purpose? The role of clinical trials is to sort through the thousands of ideas ( for drugs, medical procedures and devices) developed every year and select those that will have actual benefits to patients without toxic or minimal side effects.

4. Examples Of Clinical Trials: The typical and most common example is the validation (tests the effectiveness of and identifies the negative side effects) of new drugs developed against human diseases. In addition to drugs, other medical procedures (for ex.; using new surgery techniques or instruments during surgery) or medical devices (implants, pacemakers, etc.) are also validated in clinical trials. Prevention strategies for a disease can also be the subject of a clinical trial.

5. The Tragic Story Of Thalidomide What Happens if a clinical trial is not properly carried out? A cautionary tale of the dangers of forgoing testing. In the late 1950s and early 1960s, pregnant women in Europe and other countries were given the drug Thalidomide to prevent morning sickness or anxiety Consequently, more than 10,000 children were born with deformities. In the USA, the Food and Drug administration (FDA) had not made Thalidomide available. FDA officer, Dr. Frances Oldham Kelsey, strongly opposed the drug approval because clinical testing had been inadequate.

6. How New Ideas For Clinical Trials Develop Usually come from researchers in academic or research settings. The most promising new compounds, devices or procedures are moved into pre-clinical and clinical trials.

7. Developing A New Medical Procedure Phase III Idea Preclinical trial Phase I Phase I I Phase IV FDA* Approval FDA* Approval Production Marketing From Bench to Bed *FDA: Food and Drug administration

9. Terms To Know: Food and Drug Administration (FDA): a branch of the U.S. Department of Health and Human Services agency responsible for ensuring the safety and effectiveness of all drugs, vaccines and medical devices. It also protects our nation’s blood supply.

10. More Terms: Control – may be a placebo (an inactive, harmless pill, powder or treatment) or the current established treatment of choice. It will be compared to the experimental procedure, drug or device.

11. More Terms: Toxicity: an adverse effect produced by a drug that is detrimental to a client’s health. Remember – “ It’s the dose that makes the poison.”

12. What Are Clinical Trial Protocols? A Clinical Trial Protocol is a document that describes such things as the objectives, design, methods, organization of a clinical trial, etc. Designed to safeguard the health of the participants and to guarantee that the trial is scientifically solid. It describes such things as who may participate, how the study will be conducted and why each part of the study is necessary.

13. Randomized Control Trials (CRT) Randomized Trials: A study in which participants are randomly assigned (i.e., by chance) to the arms (different groups) of the clinical trial. Most clinical studies are conducted as randomized trials.

14. Double Blind Trial In addition to randomizing the patients, most clinical studies are carried out following the procedure know as a “Double Blind” study.

15. Double Blind Studies: A clinical study in which neither the participants nor the study staff know which clients are receiving a placebo and which are receiving the trial medicine. It increases the objectivity of the study since the expectations of the doctors and participants do not adversely affect or bias the study. What is a double blind study?

16. Why Does It Take So Long? In order to assure a thorough evaluation of a drug or medical procedure, the clinical trials are usually performed in stages (phases). Why is this done?:  For safety reasons and to improve the quality of the research.  For economical purposes.

17. Example of a Phase III study in Breast Cancer Protocol development and approval Patient recruitment Patient recruitment Randomization Placebo + Letrozone (Control) Placebo + Letrozone (Control) Lapatinib + Letrozone (Experimental) Lapatinib + Letrozone (Experimental) Patient evaluation Statistical analysis Patient evaluation Statistical analysis

18. As we can see, clinical trials are not only expensive but also take a long time. The clinical trials for most drugs, procedures or medical devices usually take more than 10 years before they are approved by the FDA and can be marketed.

19. Patient Recruitment

20. Who Participates in Clinical Trials : Only volunteers - nobody can be forced into participating in a clinical trial. Economical incentives can be used, however; they can not be so large as to provide someone with an incentive to do something he or she would not normally do. Recruitment is done strictly following the clinical trial protocol (age, gender, clinical conditions, etc.)

21. Informed Consent An agreement that describes the rights of the participant and the details of the studies. Risks and benefits are explained; the participant then decides whether or not to sign.

22. May benefit one’s own health. Can gain access to medical treatment before it’s available to the public. Can benefit others by your participation.

23. What Are the Risks of Participating? May have unpleasant, serious or even life- threatening side effects. You may be randomized into a placebo group or the treatment in the experimental group may not be as effective as you had hoped. The protocol may require more of your time & attention then you have available.

24. How Am I Protected? Clinical Studies are governed by the same medical/ethical codes used in medicine. Federal regulations, as well as the safety and ethics of the study, are reviewed by the Institutional Review Board (IRB). IRB approval is mandatory for any study involving humans. Every participant has to sign an informed consent where information on the clinical trial is provided as well as the potential risks to the participant. Results (but not names) for each participant are given to federal agencies, medical journals and/or medical associations (your identity is protected).

25. Some Examples Of Things To Ask When Considering Participation In A Clinical Trial: Why is the study being conducted? Why do the researchers believe this particular treatment would be effective? What are the side effects or possible risks? How much time is involved? How long will it last? What recourses do I have if I experience negative side effects ?

26. Can I Leave a Trial If I Experience Negative Side Effects? Yes – but you need to let the research team know when you’re leaving and why. However, be aware, it may adversely affect the outcome of the study (ex.; sample size too small).

27. Want To Participate In A Clinical Trial? Want To Know More? GO TO: WWW.ClinicalTrials.Gov

28. The end

29. Clinical Trials

31. Study Protocols

32. PhaseStudy Sample SizePurposeDuration PreclinicalNo human subjects Tissue Cultures and animal studies Conduct molecular studies and animal trials. 3-4 years Phase ISmall sample of 20-100 patients Assess safety, toxicity and drug behavior. 3-4 years Phase IISmall number of patients affected with the disease Assess treatment effectiveness and adverse effects and determine optimal doses. 3-4 years Phase IIILarge number of patients with the disease Compare new treatments to the current standard of care. 4 years FDA approvalFDA officials review all the information Approve drugs or treatments that are considered safe and efficient..5-2 years Phase IVN/AFind adverse effects while drug is in the market Indefinite