All research begins with an idea or a question, typically generated by researchers in labs. A clinical trial is a research study performed on humans that aims to answer a specific health-related question, or that is done to evaluate the safety and efficacy of a potential treatment.
Certain interventions such as medications are tested first on animals (usually mice). If the animal tests seem promising, then the researchers can take the next step towards testing the treatment on humans in a clinical trial.
According to the National Institutes of Health, there are six categories of clinical trials:
- Quality of Life Trials: test interventions that aim to improve comfort, promote independence, and/or improve the overall lifestyle of those living with chronic illness.
- Screening Trials: aim to identify effective ways to screen for disease.
- Prevention Trials: aim to identify effective ways to prevent disease from occurring.
- Treatment Trials: test new treatments such as medications or procedures that can be used to treat or cure illness.
- Diagnostic Trials: aim to develop better and/or more efficient tests for diagnosing disease.
- Natural History Studies: explore how disease develops and progresses.
Declaring the Rules
Once researchers are ready to move ahead with a clinical trial they are required to take several important steps before beginning. First, they’ll design the study’s protocol. The study must be acceptable and feasible. This means that people will actually want to participate, and that the intervention can be done relatively easily.
They must know in advance the following:
- Who will be allowed to participate
- How they will administer their interventions
- Where the trial will be conducted
- How long it will run
- Who the lead investigator is
- How they will monitor the participants’ health
They will also outline how they’ll measure whether the intervention is safe, effective, and feasible.
In the United States the protocols for all studies must be reviewed and approved by the Institutional Review Board (IRB). The IRB is responsible for ensuring that all trials are ethical; that the risks to the subjects are minimal; and when there is more than minimal risk to the participant, whether the benefits outweigh the risks. They also ensure that the rights of the research participants are protected, that all of their data is stored confidentially, and that their participation does not affect the quality of their medical care should they decline to participate.
In order to get off the ground, a trial needs funding. Running a clinical trial is an expensive undertaking. Researchers typically apply for grants in order to finance their trials. Grants are lump sums of money that are given out by public organizations such as the National Institutes of Health (NIH), foundations, or private donors in order to fund research. These public institutions have a yearly budget, and therefore can only finance a small portion of the clinical trials that are waiting to be done. For example, the Congressionally Directed Medical Research Program for Multiple Sclerosis received 37 applications in 2012, but could only fund six trials. Pharmaceutical companies, organizations, and individuals can also cover the cost of running a clinical trial.
If a trial is approved by the IRB and receives enough funding, then it can move forward and start to recruit participants. Everyone who participates in a clinical trial must sign an informed consent document. This form ensures that the participant understands the details of the study, how long it will last, what procedures are required, whom to contact for more information, and the risks and benefits of participating. Participants also reserve the right to refuse treatments or tests and to withdraw from the study at any time with no detriment to their medical care.
Running the Trial
A clinical trial for a treatment is ready to begin once it has IRB approval, funding, participants, and investigators (usually doctors) to run the trial. Trials can last for several years, and are conducted in a series of phases:
- Phase I Trials: Researchers test treatments on a small group of 20-80 people. They use their data to evaluate the treatment’s safety, and they observe for side effects.
- Phase II Trials: The treatment is now administered to a larger group of 100-300 people and data is used to determine whether it is effective and how safe it is.
- Phase III Trials: The treatment is administered to an even larger group of 1,000-3,000 people. Effectiveness, side effects, and safety are all evaluated. During this phase, researchers compare the treatment to other already available treatments (i.e. they will compare a trial drug to another drug that is already on the market). Some phase three clinical trials also compare different routes of administration of the same drug (i.e. investigating whether a drug given via IV is also safe and effective when given as a subcutaneous injection).
- Phase IV Trials: This phase occurs after the US Food and Drug Administration (FDA) has approved a treatment and it is made available to the public. Data will continue to be collected for up to 10 years.
Reviewing the Data
Once the trial is complete and enough data is collected on the treatment, the researchers can analyze the results and determine if they are of medical importance. If so, they will then write up their clinical trial for publication in a peer-reviewed journal, such as the New England Journal of Medicine. Once the information is submitted to a journal, it will be evaluated by several independent researchers who are considered to be experts in their field. This panel of experts will evaluate the rigor of the study and ensure that the analysis and conclusions of the trials are accurate before they are published.
In order for an investigational drug to be made available to the public, the researchers must submit their data to the Food and Drug Administration (FDA). The FDA will carefully review the design of the trial, the side effects that were observed, the benefits of the drug, the validity of the data collected, and how the drug is manufactured. They will then determine if the benefits of the drug outweigh the risks. The FDA can either approve or deny the treatment, or request that the researchers collect more data before reaching a decision. According to the FDA, their process typically takes 6 – 10 months.
It can take up to 15 years for a drug to move through all of the phases and make it to market. When developing a drug, it can take 3-6 years to research and ready the product to be tested on humans, then an additional 6-7 years to go through phases 1-3. FDA review then takes between six months and two years, and phase four runs after the drug hits the market and can go on for as long as 10 years.
Stephanie Buxhoeveden MSCN, FNP-BC
Stephanie is a nurse practitioner who was diagnosed with MS at age 25. Shortly after being diagnosed she realized she could use her experiences as a patient to make a difference in the lives of others, so she became a multiple sclerosis certified nurse. Stephanie completed her master’s in nursing at Rutgers University, and now specializes in the care of people with MS and other neurological diseases.
Her blog, www.justkeepsmyelin.com, offers a unique perspective on MS from both a healthcare provider’s point of view, and through the eyes of a person living with the disease every day. Her mission is to bring compassion, humor, and a deeper understanding of MS to anyone who reads it. She also writes for MultipleSclerosis.net, MSFocus Magazine, serves as a District Activist Leader for the National MS Society and is on the membership committee of iConquerMS.
Article resources:clinical trials, MS, ms treatments, multiple sclerosis