7. Clinical Research

Clinical research is a process to find new and better ways to understand, detect, control and treat health conditions. The scientific method is used to find answers to difficult health-related questions.

Types of clinical studies:

• Observational study: A type of study in which people are observed or certain outcomes are measured. No attempt is made by the researcher to affect the outcome. For example, researchers may collect data through medical exams, tests, or questionnaires about a group of older adults over time to learn more about the effects of different lifestyles on cognitive health. These studies may help identify new possibilities for clinical trials.
• Clinical trial (interventional study): During clinical trials, researchers learn if a new test or treatment works and is safe. Treatments studied in clinical trials might be new drugs or new combinations of drugs, new surgical procedures or devices, or new ways to use existing treatments. 
• Medical records research. Medical records research involves the use of information collected from medical records. By studying the medical records of large groups of people over long periods of time, researchers can see how diseases progress and which treatments and surgeries work best

Types of clinical trials:

There are many types of clinical trials:

• Prevention studies look at ways to stop diseases from occurring or from recurring after successful treatment.
• Screening studies compare detection methods for common conditions.
• Diagnostic studies test methods for early identification of disease in those with symptoms.
• Treatment studies test new combinations of drugs and new approaches to surgery, radiation therapy and complementary medicine.
• The role of inheritance or genetic studies may be independent or part of other research.
• Quality of life studies explore ways to manage symptoms of chronic illness or side effects of treatment.
• Medical records studies review information from large groups of people.

Clinical Research Phase Studies

Phase 0 clinical trial:

Phase 0 involves exploratory, first-in-human (FIH) trials that are run according to FDA guidelines. Also called human microdose studies, they have single sub-therapeutic doses given to 10 to 15 subjects and yield pharmacokinetic data or help with imaging specific targets without introducing pharmacological effects. Pharmaceutical companies perform Phase 0 studies to decide which of their drug candidates has the best pharmacokinetic parameters in humans.

Phase 1 clinical trial:

Study Participants: 20 to 100 healthy volunteers or people with the disease/condition.

Length of Study: Several months

Purpose: Safety and dosage, absorption and metabolism, effects of organs and tissues.

Approximately 70% of drugs move to the next phase

In this phase it is important to enroll a relatively healthy patient population with as few complications and concomitant diseases as possible.

Food effect studies are often conducted to investigate the potential impact of food intake on the absorption of the drug. These studies are usually run as a crossover study, with volunteers being given two identical doses of the drug, one after fasting and one after a meal.

Phase 2 clinical trial:

Study Participants: Up to several hundred people with the disease/condition.

Length of Study: Several months to 2 years

Purpose: Efficacy, short term side effects and dose range

Approximately 33% of drugs move to the next phase

Phase 3 clinical trial:

Study Participants: 300 to 3,000 volunteers who have the disease or condition

Length of Study: 1 to 4 years

Purpose: Efficacy and monitoring of adverse reactions

Approximately 25-30% of drugs move to the next phase

Phase 4 clinical trial:

Study Participants: Several thousand volunteers who have the disease/condition

Purpose: Benefit/risk relationship of drug, Less common and longer term side effects and Labeling information.

Here’s what happens in a trial:

• Clinical trial sponsors, usually pharmaceutical companies, are responsible for developing the clinical trial protocol. 
• The protocol describes every aspect of the research, including the rationale for the experiment, objectives, trial population with detailed inclusion and exclusion criteria, administration of the investigational therapies, trial procedures, data collection standards, endpoints and sample size. 
• The Informed Consent Form (ICF) is used to disclose current information about the investigational drug and about the procedures, risks and benefits for subjects who participate in the clinical trial. 
• In addition to the protocol and the ICF, sponsors are responsible for setting up and maintaining clinical databases for the data collected in the trial. 
• Case Report Forms (CRFs) are designed by the sponsor as data collection tools. These tools are increasingly based on electronic data capture modules via the internet rather than the traditional paper-based route. 
• If any patient wants to enrol in clinical trial, investigators educate them about the trial participation to ensure that they can make an informed decision and study staff gather more information about the patient.
• If patients had any questions they can ask to study team or physician (investigator). 
• Once patient have had all questions answered and agree to participate, the patient sign an informed consent form.
• The patients are screened to make sure they qualify for the trial. The screening may involve cognitive and physical tests. 
• Inclusion criteria for a trial might include age, stage of disease, sex, genetic profile, family history, and whether or not you have a study partner who can accompany you to future visits. Exclusion criteria might include factors such as specific health conditions or medications that could interfere with the treatment being tested.
• If accepted into the trial, the patient schedule a first visit (called the “baseline” visit). The researchers conduct cognitive and/or physical tests during this visit.
• The patients are randomly assigned to a treatment or control group.
• The patient have to follow the trial procedures and report any issues or concerns to researchers.
• The patient may visit the research site at regularly scheduled times for new cognitive, physical, or other evaluations and discussions with staff. At these visits, the research team collects information about effects of the intervention and patient safety and well-being.
• The patient continue to see their regular physician for usual health care throughout the study.
• The collected data is stored in clinical trial database. If any safety concerns/adverse events are noted then information  sent to pharmacovigilance team who submits reports on adverse events during clinical trials to regulatory authorities within a specified time frame, notification of such events to all investigators and ethics committees. 
• Annual reports, a summary and analysis of all the serious adverse events, new safety findings from animal studies, and evaluations of benefit and risk are also prepared and submitted by PV team. 

Why Participate in a Clinical Trial?

The subjects in trials become a partner in scientific discovery and their contribution can help future generations lead healthier lives. Major medical breakthroughs could not happen without the generosity of clinical trial participants—young and old.

There are many reasons why people choose to join a clinical trial. Some join a trial because the treatments they have tried for their health problem did not work. Others participate because there is no treatment for their health problem. Some  join due to financial issues. By being part of a clinical trial, participants may find out about new treatments before they are widely available. 

Questions to ask before participating in a Clinical trial: 

The following are some questions to ask the research team when thinking about a clinical trial. 

• What treatment or tests will I have? Will they hurt?
• What are the chances I will get the experimental treatment?
• What are the possible risks and side effects, and benefits of the study treatment compared to my current treatment?
• How will I know if the treatment is working?
• How will you protect my health while I am in the study?
• What happens if my health problem gets worse during the study?
• How will the study affect my everyday life?
• How long will the clinical trial last?
• Where will the study take place? Will I have to stay in the hospital?
• Will you provide a way for me to get to the study site if I need it?
• Will being in the study cost me anything? If so, will I be reimbursed? Will my insurance cover my costs?
• Can I take my regular medicines while in the trial?
• Who will be in charge of my care while I am in the study? Will I be able to see my own doctor?
• Will you follow up on my health after the end of the study?
• Will you tell me the results of the study?
• Whom do I call if I have more questions?
• How will you keep my doctor informed about my participation in the trial?
• Does the study compare standard and experimental treatments?
• If I withdraw, will this affect my normal care?
• What are the chances that I will receive a placebo?
• What steps ensure my privacy?

Where Can you Find a Clinical Trial?

You can talk to your doctor or other healthcare provider. Or, you can search ClinicalTrials.gov. You can sign up for a registry or matching service to connect you with trials in your area. Support groups and websites that focus on a particular condition sometimes have lists of clinical studies.

How the clinical trial information communicated:

• Clinical trials generate data that contribute to the body of knowledge about the treatment and the disease that benefit the broader medical community and, ultimately, the patients.
• Safety information of one product may be informative to other practitioners using a similar class of agents.
• ClinicalTrials.gov was created and it allows sponsors and principal investigators to submit the results of clinical studies.
• The mandatory requirement on clinical trial registration and the disclosure of trial results are significant achievements in advancing science and increasing transparency in clinical research

Clinical development success rates in past 10 years:

• Only 5 in 5,000 drugs that enter preclinical testing progress to human testing. One of these 5 drugs that are tested in people is approved. The chance for a new drug to actually make it to market is thus only 1 in 5,000.
• Cancer drugs have the lowest overall rate of success, with just 5.1 percent of drugs that enter Phase 1 trials ultimately reaching FDA approval. The highest success rate, of 26.1 percent, is seen in blood-related conditions like hemophilia, anemia and blood protein deficiencies.
• As in past studies, Phase 2 trials are where most drugs fail. Only 31 percent of drugs that enter Phase 2 studies go on to Phase 3, either due to failure of the study or lack of funding.
• Drugs for rare diseases are far more likely to succeed, with 25 percent of rare disease drugs that enter clinical trials getting FDA approval. The lowest rates of success are seen in chronic diseases with large patient populations, which have an average success rate of 8.7 percent.
• 58 percent of drugs that begin Phase 3 trials are later submitted to the FDA for approval, a rate the study calls “concerning” because 35 percent of all research and development costs — and 60 percent of all clinical trial costs — go toward large Phase 3 trials.