Two of the most common topics of discussion in the migraine community are migraine treatments and what a migraine really is, what’s going on in our bodies during a migraine attack. Both new treatments and understanding the pathophysiology of migraine depend upon clinical studies, so it benefits us to know the basics of clinical studies.
A clinical study involves research using human volunteers (also called participants) that is intended to add to medical knowledge. There are two main types of clinical studies:
- clinical trials (also called interventional studies) and
- observational studies.
Every clinical study is led by a principal investigator, who is often a medical doctor. Clinical studies also have a research team that may include doctors, nurses, social workers, and other health care professionals. Some clinical study teams also include patients as co-investigators or advisors.
Clinical studies can take place in many locations, including hospitals, universities, doctors’ offices, and community clinics. The location depends on who is conducting the study. The length of a clinical study varies, depending on what is being studied. Participants are told how long the study will last before they enroll.
Clinical studies can be sponsored, or funded, by pharmaceutical companies, academic medical centers, voluntary groups, and other organizations, in addition to federal agencies such as the National Institutes of Health (NIH), the U.S. Department of Defense, and the U.S. Department of Veterans Affairs. Doctors, other health care providers, and other individuals can also sponsor clinical research.
A clinical study is conducted according to a research plan known as the protocol. The protocol is designed to answer specific research questions and safeguard the health of participants. It contains the following information:
- the reason for conducting the study;
- who may participate in the study (the eligibility criteria);
- the number of participants needed;
- the schedule of tests, procedures, or drugs and their dosages;
- the length of the study; and
- what information will be gathered about the participants.
In a clinical trial, participants receive specific interventions as specified in advance in the trial plan or protocol created by the investigators. These interventions can take several forms:
- medical products, such as medications or devices;
- procedures, such as nerve blocks, sphenopalatine ganglion blocks, or surgery; or
- changes to trial participants’ behavior, such as diet, sleep patterns, or cognitive behavioral therapy.
Clinical trials may compare a new medical approach to a standard one that is already available, to a placebo that contains no active ingredients, or to no intervention. Some clinical trials compare interventions that are already available to each other. When a new product or approach is being studied, it’s not usually known whether it will be helpful, harmful, or no different than available alternatives (including no intervention). Trial investigators try to determine the safety and efficacy of the intervention by measuring certain outcomes in the participants. For example, investigators may give a medication or treatment to participants who have migraine to see whether their migraine frequency decreases.
Clinical trials for medication development have several phases that are defined by the Food and Drug Administration (FDA). The phases are:
- Phase 0: Exploratory study involving very limited human exposure to the medication, with no therapeutic or diagnostic goals (for example, screening studies, microdose studies)
- Phase 1: Studies that are usually conducted with healthy volunteers and that emphasize safety. The goal is to find out what the medication’s most frequent and serious adverse events are and, often, how the drug is metabolized and excreted.
- Phase 2: Studies that gather preliminary data on effectiveness (whether the medication works in people who have a certain disease or condition). For example, participants receiving the medication may be compared to similar participants receiving a different treatment, usually an inactive substance, called a placebo, or a different medication. Safety continues to be evaluated, and short-term adverse events are studied.
- Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the medication in combination with other medications.
- Phase 4: Studies occurring after the FDA has approved a medication for marketing. These include postmarket requirement and commitment studies that are required of or agreed to by the study sponsor. These studies gather additional information about a medication’s safety, efficacy, or optimal use.
This video provides a simple view of clinical trials and some of the phases:
In an observational study, investigators assess health outcomes in groups of participants according to a research plan or protocol. Participants may receive interventions (which can include medical products such as medications or devices) or procedures as part of their routine medical care, but participants are not assigned to specific interventions by the investigator (as in a clinical trial). For example, investigators may observe a group of older adults to learn more about the effects of different lifestyles on cardiac health.
Questions to ask before participating in clinical studies:
Anyone interested in participating in a clinical study should know as much as possible about the study and feel comfortable asking the research team questions about the study, the related procedures, and any expenses. The following questions may be helpful during such a discussion. Answers to some of these questions are provided in the informed consent document, which every study participant must sign. Many of the questions are specific to clinical trials, but some also apply to observational studies.
- What is being studied?
- Why do researchers believe the intervention being tested might be effective? Why might it not be effective? Has it been tested before?
- What are the possible interventions that I might receive during the trial?
- How will it be determined which interventions I receive (for example, by chance)?
- Who will know which intervention I receive during the trial? Will I know? Will members of the research team know?
- How do the possible risks, side effects, and benefits of this trial compare with those of my current treatment?
- What will I have to do?
- What tests and procedures are involved?
- How often will I have to visit the hospital or clinic?
- Will hospitalization be required?
- How long will the study last?
- Who will pay for my participation?
- Will I be reimbursed for other expenses?
- What type of long-term follow-up care is part of this trial?
- If I benefit from the intervention, will I be allowed to continue receiving it after the trial ends?
- Will results of the study be provided to me?
- Who will oversee my medical care while I am participating in the trial?
- What are my options if I am injured during the study?
Clinical studies are crucial to building knowledge about migraine disease and to developing new treatments. Clinical trials of medications and devices are necessary for FDA approval. Surgical procedures don’t go before the FDA for approval, but before we agree to and schedule any of the surgical procedures for migraine that we so often hear about, we should be sure that there have been adequate and properly run clinical trials to prove both their efficacy and safety.
More helpful articles:
Learn About Clinical Studies. ClinicalTrials.gov. January, 2017.
Glossary Definition: Phase. ClinicalTrials.gov.
Teri Robert is a leading patient educator and advocate and the author of Living Well with Migraine Disease and Headaches. A co-founder of the Alliance for Headache Disorders Advocacy and the American Headache and Migraine Association, she received the National Headache Foundation’s Patient Partners Award and a Distinguished Service Award from the American Headache Society. Teri can be found on her website, and blog, Facebook, Twitter, StumbleUpon, Pinterest, LinkedIn, and Google+.