DSI Newsletter: How Drugs are Studied

DSI Newsletters, Issue 66:
How Drugs are Studied

How Will Treatment in a Clinical Research Study Differ from the Treatment Your Own Doctor Provides?
Clinical research often involves providing treatment. Yet, treatment research is different from the care that you would get from your own doctor. Usually, when you go to a doctor, you want help with a particular problem. You count on your doctor to do what is best for you. You know that anything your doctor suggests is meant to make you well. Ideally he has all the time in the world to spend with you providing you with thorough explanations concerning your particular medical condition, how to treat it, which treatment options are available, and how to prevent that particular aliment along with other ailments from affecting you in the future.
A treatment research project, however, is different. The investigator (the doctor conducting the clinical research) wants to learn about your illness, and not just treat you. Of course, a researcher will try very hard to see that you benefit from the treatment research and that any risk will be small. Yet one goal remains important: learning how well a new treatment works for someone with your illness while assuring the patient that has stepped forward to volunteer for an experimental drug study that they understand all the risks, benefits and alternative procedures and are safeguarded from harm and helped as much as possible.
In research, the design of a study may call for standardized procedures. For instance, when a researcher studies a medicine, or drug, the research plan may require that only the drug under study be available to you. It may mean that you will receive it only in a fixed dose; that is, the researcher cannot tailor the amount of a medication to your immediate needs. Or, standardized procedures may mean that you will receive a medication only in one specific way for example, by a shot or as a pill.
In such a study, or drug trial, the treatment you will receive likely will be based on your random assignment to a particular medication or, sometimes, to an inactive pill (a placebo). You will be told what is known about the relative benefits and risks of each treatment used in the research study. You will also be told what is known about alternative treatments that might be given outside a research project. In contrast, treatment outside of a research study seldom uses random choice of treatment and never uses a placebo; your doctor will always prescribe a treatment that he or she believes would be good for you. However, situations remain where no one may know what treatment is best, and that is one instance where the importance of research is clear.
The placebo effect can be enormous. If a doctor gives you an M and M and reassures you that your illness will be cured, it will be about 40% of the time. Like wise if you are concerned that a particular treatment will cause a side effect it will about 40 % of the time. This is the problem with the untested "alternative medicines" one can purchase without a prescription that seem to have no side effects. That is, because they were never formally studies. If you compare placebo A to placebo B, there will be about 40% incidence of side effects (adverse events) that are associated with them. And sometimes treatments that we "suspect" are better than placebo are proven to worse. Take for example the case of the antiarrhythmic drug Enkaid or the hormone Premarin which have a higher chance of mortality than placebo. The relative risks and benefits would not be known if someone didn't step forward and volunteer to help study them. Modern medicine can not move forward without placebo controlled trials and the person who volunteers for them is held in the highest esteem by medical researchers and is protected and cared for with extreme diligence.
It should help to know that even investigational treatments are well-tested for safety before their use in a clinical study. Also, remember that you always can decide to withdraw from a study. You, or someone close to you, should know whom to contact if you want to do so at any time.
Checklist of Questions for Clinical Trials Participants
So you have been asked to take part in a research study! This can be a very satisfying experience, allowing you to help yourself now and to help others in the future. After all, without research, treatment cannot improve, and without those who take part, there would be no research! You are the one who makes research possible.
But how do you know if you want to take part? What questions should you ask? The researcher should answer these basic questions clearly for you. Others undoubtedly will arise during the discussion.

Why do you want me in your study?
What is the research about? How will this research help in treating or understanding my disorder?
What do I need to do and how much time will this take?
How might this study help me, my relatives, or other people with my disorder?
What possible risks are there to me or my relatives if I take part?
How will this be different from the care I am getting now, and do I have other options or choices?
Could my illness become worse during the study? What will happen if it does?
What will happen to me at the end of the study?
What should I do if I want to drop out of the study?
May I get back to you after I discuss this with my family/friend/case manager/doctor?

Remember to ask again if you do not understand the explanation to any question you have. And, if you forget the answers to these questions during the study, just ask them again. The research doctor will be happy to spend all the time you and your family require to feel good about volunteering.
What is a Placebo Controlled Trial?
Studies of new drugs often compare the effects of an investigational drug with the effects of a placebo. If you are considering whether to take part in a drug trial, the director of the study must tell you if the study will use a placebo control. The informed consent form that you will sign if you agree to join the study must also explain any plans to use a placebo control.
The reason for using a placebo control is that the benefits and side effects from taking medications are not always due to the drug itself. These benefits and side effects are called "placebo effects." An example is when an investigator's enthusiasm about a new medication sometimes influences (biases) the patient’s response.
A researcher must be able to separate placebo effects from the actual effects of the drug being studied. When equal numbers of patients receive either a placebo or another standard drug that will help treat their symptoms, the researcher can better judge the actual effects of the drug being tested.
In a "double-blind, placebo-controlled" research design, the doctors and nurses working directly with patients in the study will not know which group patients are in. Only members of the research team not involved in providing day-to-day clinical care will know which patients are receiving an active treatment or a placebo. The DSMB (Data Safety Monitoring Board) has access to all the information. This information is shared only when there is a medical necessity to do so to protect the patient and at the end of the study. The double-blind, placebo controlled trial is considered the gold standard. Anything less has biases that can effect the results and lead to error like allowing a potentially dangerous drug on the market.
Some scientists have questioned the use of placebo controls in clinical research. They argue that if any drug is effective in treating a given condition, then only that drug, and not a placebo, should be given as the control. Other researchers, however, believe that without a placebo control, it is harder to know whether an investigational medication is better than existing drugs. The choice depends on what is being studied, the medicine, and the illness.
If, during a study, an investigational drug seems to work very well, the researcher may stop using the placebo. In some instances participants may have a chance to use the investigational drug after a study is completed. This is referred to as an extension trial. Here as a reward for helping the drug company in the double-blind portion, everyone receives the real drug in an open label fashion usually for a year to say thank you for participating and to obtain data on long term use.
It is important that the director of a medication trial explain thoroughly any planned use of a placebo. Ask how the researcher plans to keep track of your symptoms. Also, ask if there is a possibility that your symptoms could become severe during the research project. If your symptoms worsen, at what point will the researcher decide to remove you from the study and provide standard treatment? In talking about these possibilities with the researcher, you must remember that participating in a study does not guarantee that you will receive a promising new medication. Indeed, you must consent to that fact. Also, you should remember that even if you receive an investigational drug, it may not be helpful for you. Remember you can always withdraw from a study for any reason at any time without any loss of benefits that you might have enjoyed prior to beginning the study.
The one benefit you receive in a clinical trial is education. You medical condition is thoroughly explained to you along with all the possible alternatives. Risks that are very rare are included especially is they are severe. For example, we routinely tell subjects that looking at the needle when we draw blood could be deadly. It sounds hard to believe but some people get faint when the look at a needle and could faint and hit there head and be injured. Well these things are described in what’s called the ICF (Informed Consent Form).
People who volunteer for a clinical trial are given more time to explain and educate them regarding there particular health issue. This education empowers them to make improved healthcare decisions for the rest of their life.
In conclusion, placebo really does make the world go round. It is related to the saying, "perception is reality."

Sincerely:
Joseph Saponaro, MD, DABIM, FACP, CPI, CCI, CCTI, CCRC, CCRP
PI (Principal Investigator), DSI (Drug Study Institute)
Board Certified Internist, JPMC (Jupiter Preventive Medicine Center)
DABIM (Diplomat American Board of Internal Medicine)
FACP (Fellow American College of Physicians)
CPI (Certified Physician Investigator) by the AAPP (American Academy of Pharmaceutical Physicians)
CCTI (Certified Clinical Trial Investigator) by the ACRP (Association of Clinical Research Professionals)
CCI (Certified Clinical Investigator) by the DIA (Drug Information Association)
CCRC (Certified Clinical Research Coordinator) by the ACRP (Association of Clinical Research Professionals)
CCRP (Certified Clinical Research Professional) by SoCRA (Society of Clinical Research Associates)
Member, SIMPD (Society for Innovative Medical Practice Design)
Member, ACPM (American College Preventive Medicine)
Ethics Committee Member, Jupiter Medical Center
IRB Member, Jupiter Medical Center
Founder, CertifiedResearchers.com

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