Who conducts a clinical trial?

There are many different people involved with conducting clinical trials, with each person responsible for doing their part to ensure the completion of a safe and efficient study.  Some of the positions include the following:

• Principal Investigator (PI)
• Responsible for the conduct of the clinical trial at the study site
• Assumes overall responsibility for the management of the study
• Assigns responsibilities for other members of the team
• Ensures that informed consent is properly obtained from the study volunteers
• Serves as the liaison for major patient care issues with the sponsor and the institutional review board (IRB), an oversight committee, and ensures that the IRB is informed of all safety issues
• Makes medical assessments, evaluating the efficacy of the study medication and whether adverse events are study related or not
• Ensures the accuracy of the data that are submitted
• Subinvestigators
• Assume the responsibility for patient care assessments
• Less likely to be saddled with the administrative responsibilities of the PI
• Clinical Research Coordinator or Study Coordinator
• In charge of managing the individual study site
• Helps assess study feasibility
• Handles, prepares and tracks document submission
• Manages the day-to-day logistics of everything

Who else is involved in a clinical trial?

• Subjects
• Trial participants
• Also referred to as patients or volunteers
• Institutional Review Board (IRB)
• Committee designated to review the participation of subjects in research studies
• Oversees the regulatory, ethical and safety aspects of a trial at the individual study site
• Decides what constitutes informed consent
• Food and Drug Administration (FDA)
• Department of the U.S. government
• Provides regulatory oversight for the pharmaceutical industry
• Provides assurances to the public for the quality and safety of all the drugs dispensed in the U.S.
• Sponsors
• Pharmaceutical company (drug company)
• Group who controls the finances
• Develops the drug, overseeing its growth from initial identification of the chemical entity through manufacturing and testing of the product in people.
• Provides management of the trial
• Designs the trial
• Provides materials
• Collects data
• Monitors the trial
• Audits all procedures and data submitted to support the application for approval from the government
• Keep investigators informed of new information about the trial drug

The sponsor's team may include the following positions:

• Clinical Research Associate (CRA)
• Often referred to as the monitor
• Acts as an agent of the drug company
• Monitor how the trial is being conducted at the study sites
• Medical Research Associate (MRA)
• Functions like a CRA, but is in-house at the sponsor's facility
• Medical Monitor
• Physician on call for protocol questions or safety issues
• Ideally, knows something about the investigational area in question
• Should be willing to learn on the job

Information taken from "Conducting Clinical Research" by Judy Stone, M.D. Copyright 2006.

Phases of Drug Development in Clinical Trials

The processes involved in a clinical trial can vary greatly depending on which phase of the study is currently active, from the number of people being studied to the length of each phase.

• Early Development
• Phase 1
• Phase 2
• Phase 3
• Phase 4

Early Development - lasts 3-6 years

This phase is intended to study a drug's action and metabolism and to evaluate the drug for obvious toxicities before it is given to people.

• Preclinical development
• Test tube or computer-based discovery
• New agents are tested in animals, typically mice or rats
• Drugs are then tested in larger animals, such as dogs
• Permission to test the drug in humans is then requested from the FDA
• If permission is granted, then the clinical research in humans can begin

Phase 1 - lasts months

• 20-100 healthy volunteers are given increasingly larger amounts of the study drug
• Tests the following for the study drug:
• safety
• tolerability
• pharmacokinetics (how long the drug lasts in the body; details about its distribution, metabolism and excretion)
• pharmacodynamics (details of the drug's activity)

Phase 2 - lasts months to years

• Hundreds of patients are given the study drug
• Patients are generally not very ill, nor do they typically have many other conditions or take many other medications that could interfere with the effects of the study drug
• Sponsor determines effectiveness of drugs for its intended use
• Tries to find the best dose for condition
• May include comparator drugs or a placebo to study the differences in results between the current treatment plan and the drug being studied

Phase 3 - lasts 2-3 years

• Thousands of patients are given the study drugs at multiple study sites.
• Studies the effectiveness and safety of the drug on a larger scale
• Includes more real-world patients who have other medical problems in addition to the one being studied
• Patients receive either the new study drug or medication that is already on the market
• Depending on the study, one group may receive a placebo (fake medication or no treatment)
• Placebos are never given to seriously ill patients if an alternative therapy is available.  To do so would be both unethical and illegal.
• The Data Safety Monitoring Board can halt the trial at any time due to safety concerns or significant results showing one group is responding better to treatment than the other.

Phase 4 - lasts 3-4 years

• Number of patients in study varies
• Marketing driven
• Compares the study drug to major market competitor
• Gathers more safety information
• Attempts to expand the approved uses to other conditions
• Can lead to a change in the drug's status from prescription to over-the-counter
• May target new groups of study participants including different age, sexes or ethnicities
• After a drug is marketing, the safety of the drug is still monitored and can still be pulled from the market or have warnings added if any serious side effects are discovered

Information taken from "Conducting Clinical Research" by Judy Stone, M.D. Copyright 2006.

Physician Spotlight - Larry L. Blankenship, M.D.

    A severe case of appendicitis at the age of seven that nearly took his life led to what Dr. Blankenship refers to as the “hero worship” of his surgeon. It was this incident that sparked his interest in becoming a doctor. Never veering from the path needed to achieve his goals, this interest grew into a reality. A practicing neurologist for over 15 years, Dr. Blankenship serves as CEO of Central Indiana Neurology in Anderson in addition to his work with Community Clinical Research Center.

   Known for his hard work, Dr. Blankenship had a strong work ethic instilled in him from a young age, attributing this to his father, a steel worker. He recalls his dad facing a lot of job insecurity due to a tough economy, saying this often led to a lot of stress within his family. Having witnessed this struggle growing up, Dr. Blankenship speaks of how he prayed to God to always provide him with work, promising to never complain as long as he had the opportunity to work hard. Keeping his promise, despite a hectic schedule, he remains grateful for the opportunity and ability to work in the profession that he loves everyday.

   Despite the work and stresses doctors face, from increasing numbers of patients to decreasing insurance reimbursements, Dr. Blankenship still believes that medicine remains one of the most rewarding professions one can practice. His love for medicine can be seen in the fact that he encourages his own children to enter the field, hoping they too can have a rewarding professional experience.

   Having practiced neurology in Anderson since 1995, Dr. Blankenship began his work as a principal investigator for CCRC in 2004. He felt his involvement in clinical research would be good for the hospital, expanding its services, as well as adding a new dimension to his own practice. Specializing in neurological clinical trials, he has been involved in studying conditions such as migraines, stroke and Parkinson’s disease.

   According to Dr. Blankenship, the benefits for patients choosing to participate in clinical trials can include receiving health care options they would not have otherwise, having a greater investment in treating their disease by giving up themselves for treatment and study, as well as helping patients to come to terms with their condition. Knowing they are working toward treating their condition while helping others to learn more about the condition can also help improve the self-esteem of many patients.

   In addition to his professional achievements, Dr. Blankenship is also an accomplished musician, having played saxophone as first chair in the West Virginia High School All-State Band. He still enjoys playing when he gets the chance and also enjoys exercising.

   CCRC would like to thank Dr. Blankenship for his hard work and dedication to medicine and clinical research.

Information About Atrial Fibrillation

What is atrial fibrillation?

Atrial fibrillation is an irregular and often rapid heart rate that can lead to complications in the body. Specifically, atrial fibrillation occurs when the heart’s two upper chambers, the atria, beat irregularly, out of coordination with the two lower chambers, the ventricles. According to Americanheart.org, atrial fibrillation can be found in about 2.2 million Americans, with about 15% of strokes occurring in people with atrial fibrillation.  Below are illustrations from Mayoclinic.org that show the difference in the functioning of a normal heart and the heart of someone with atrial fibrillation.

    

Normal Heart

Atrial Fibrillation

What are the symptoms of atrial fibrillation?

Symptoms of atrial fibrillation may include palpitations (racing, uncomfortable, irregular heartbeats or flopping in your chest) of the heart, decreased blood pressure, weakness, lightheadedness, confusion, shortness of breath or chest pain. Some people with the condition have no symptoms and do not know they have it until it is discovered through a physical examination.

It is also important to note that atrial fibrillation may be occasional or chronic. Occasional atrial fibrillation involves symptoms that come and go, only lasting from minutes to hours, and stopping on their own. Chronic atrial fibrillation includes symptoms that are continuous, only stopping with treatment.


What causes atrial fibrillation?

Atrial fibrillation is caused by abnormalities or damage to the structure of the heart. According to Mayoclinic.com, these causes can include:

• High blood pressure
• Heart attacks
• Abnormal heart valves
• Congenital heart defects
• An overactive thyroid or other metabolic imbalance
• Exposure to stimulants such as medications, caffeine, tobacco or alcohol
• Sick sinus syndrome (improper functioning of the hearts natural pacemaker)
• Emphysema or other lung diseases
• Previous heart surgery
• Viral infections
• Stress due to pneumonia, surgery or other illnesses
• Sleep apnea


What factors may increase my risk for atrial fibrillation?

• Age – as you grow older, your risk of developing atrial fibrillation increases.
          – 3-5% of people over 65 have atrial fibrillation
• Heart disease – includes valve problems, history of heart attack and heart surgery
• High blood pressure
• Other chronic conditions – thyroid problems, sleep apnea, etc.
• Drinking alcohol – binge drinking puts you at an even higher risk for atrial fibrillation
• Family history


What can happen if atrial fibrillation is left untreated?

If left untreated, atrial fibrillation can eventually lead to two major complications including stroke and heart failure.

Stroke
The chaotic rhythm of the heart that occurs in atrial fibrillation may cause blood to collect in the atria and form clots. These clots can then dislodge from your heart and travel to your brain where it could potentially block blood flow, resulting in a stroke.

The risk of having a stroke due to atrial fibrillation is heightened when joined with high blood pressure, diabetes or a history of heart failure or stroke.

Heart Failure
Atrial fibrillation can weaken the heart which can lead to heart failure or a condition in which your heart cannot circulate enough blood to meet the needs of your body.


What can I do to lower my risk of atrial fibrillation?

Suggestions for lowering your risk of suffering from atrial fibrillations include:
• Stopping or reducing the amount of caffeinated and alcoholic beverages you consume
• Monitoring the over-the-counter medications you take, as some contain stimulants that can trigger atrial fibrillation
• Following a healthy diet, low in saturated fat, trans fat and cholesterol; high in whole grains, fruits and vegetables
• Not smoking
• Taking part in regular physical activity
• Maintaining a healthy weight
• Receiving regular medical care


What are the treatments for atrial fibrillation?

Treatments for atrial fibrillation can include the use of medications, electrical procedures, surgeries and catheterization.

Dr. Preetham Jetty, a leading cardiologist in the state, conducts cardiac clinical trials at Community Clinical Research Center (CCRC) in Anderson, including those that study new treatments for atrial fibrillation.

The benefits of participating in a clinical trial can include:

• Big city medicine in a small town environment.
• Access to new research treatments before they are widely available
• Study-related medication at no cost.
• Access to leading, world-class physician care
• Qualified participants will be compensated for time and travel

For more information on clinical trials, contact CCRC at 765-298-2040.