Support Clinical Trials

Educating your disease community about clinical trials can begin even before a clinical trial for your disease is ready to be opened to participants, but it is especially important when a new therapy for your disease is ready to be trialed. 

• Choose what information to include: You want to both help your disease community understand the importance of participating in clinical trials, but also provide them with general information about the clinical trial process and the importance of making an informed decision about participating.
  • Address what it means to be in a clinical trial. For example:
    • Importance of clinical trial process for therapy development. Clinical trials, unlike preclinical research, are designed to answer basic questions about the ways an investigational therapy will interact in people, especially those with a specific disease, instead of, for example, animals.
    • Essential role participants play to potentially bring new treatments to your disease community. Clinical trials help maintain a high standard of medical care across the  entire disease community, not just to the participants. 
    • Responsibilities of participants in clinical trials, including following the protocol for the trial.
  • Explain what a clinical trial is.
    • Clinical trial definition: Broadly, a clinical trial is simply a research study involving human participants, but clinical trials are only undertaken when there is reason to believe the new therapy will improve patient care, quality of life,  and other things.
    • Types of clinical trials: Clinical trials broadly fall into 2 groups, observational or interventional (also called investigational). 
      • Observational studies are just what they sound like; they observe. Generally, researchers monitor participants over a period of time and use the information to better understand the natural history of the disease. 
      • Interventional studies test the safety and effectiveness of a specific therapy to treat a specific disease or symptom associated with the disease.  
    • Phases of interventional clinical trials: Clinical trials can run from early phase 1 to phase 4, with each phase enrolling more participants. Early phase 1 trials use as few as 10 participants; phase 4 can enroll thousands. The number of required participants for each of the phases may be fewer for rare diseases. 
      • Early phase 1 trials (formerly phase 0) are exploratory studies to make certain the therapy is tolerable to humans and does not cause immediate adverse effects or serious harm.  
        • Do not include therapeutic or diagnostic goals. 
        • Enroll up to 10 healthy volunteers 
        • Run a few months (short time frame of studies).
      • Phase 1 trials are usually conducted with healthy volunteers and emphasize safety. In some circumstances, the study will enroll patients who have the disease.
        • Find out what the therapy’s most frequent and serious adverse events are.
        • Understand how the therapy  is metabolized and excreted. 
        • Determine safe levels to be administered.
        • Enroll a small group of participants, most often healthy individuals who do not have the disease.
        • Collect data for a few months.
      • Phase 2 trials gather preliminary data on the effectiveness of the therapy in patients. 
        • Continued evaluation of safety and monitoring of short-term adverse events. 
        • Determine whether the therapy works as expected in people who have a certain disease or condition. 
        • May compare participants receiving the therapy to similar participants receiving a different treatment, usually an inactive substance (called a placebo) or a different previously-approved therapy.
        • Enroll a small group of patients.
        • Collect data for a few months to 2 years. 
      • Phase 3 trials gather more information about safety and effectiveness.
        • Continued evaluation of safety and monitoring of short-term and longer-term adverse events.
        • Determine if the therapy continues to work as expected in a larger group of patients.
        • May include a more diverse patient population.
        • May include gathering data to determine the most effective dosage.
        • May use the investigational therapy in combination with other previously-approved therapies.
        • Enroll a larger group of patients.
        • Collect data for 1 to 4 years.
      • Phase 4 trials are conducted using a therapy that is newly approved by the U.S. Food and Drug Association (FDA) to continue to monitor safety and effectiveness. 
        • Occur after FDA has approved a therapy for marketing. 
        • May be a requirement of the FDA approval or due to a Sponsor commitment. Sponsors may also perform these studies voluntarily. 
        • Gather additional information about a therapy's safety, efficacy, and optimal use.
        • Enroll a large patient population, with eligibility requirements determined by the FDA approved indications.
        • Can collect data for many years.
    • Clinical trial team: A clinical trial team is made up of many different key members. The team may vary depending on several factors including the type and phase of clinical trial and whether the trial involves multiple centers. Key roles include: 
      • Principal Investigator (PI): A PI  is the lead researcher or clinician who is conducting the clinical trial. The PI is responsible for: 
        • Ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations.
        • Protecting the rights, safety and welfare of the subjects under the investigator’s care.
        • Control of the therapy(s) under investigation.
      • Clinical Research Coordinator (CRC): A CRC manages and conducts the day-to-day study activities in accordance with the protocol, applicable regulations, and Good Clinical Practice (GCP) and Institutional Review Board (IRB) requirements.
      • Sub Investigator (Sub I): The Sub I is a member of the research team designated and supervised by the PI to perform critical study-related procedures and/or to make important study-related decisions.
      • Clinical Research Nurse Coordinator (CRNC):  A CRNC may be required for certain protocol-related activities.
      • Regulatory Coordinator: The regulatory coordinator prepares and maintains IRB submissions and FDA  documents. May also track study progress. 
  • Define unfamiliar terminology. For example, the following terms may be unfamiliar to your disease community.
    • Protocol: Every clinical trial has a protocol, which is an official document that describes the study in detail. The content of protocols varies depending on several factors including the type and phase of trial. Phase 2 and 3 interventional protocols usually describe: 
      • Background and rationale for conducting the study.
      • Risk benefit assessment.
      • Objective(s), including the specific research questions being addressed.
      • Clinical trial design, including overall design, justification of dose, end of study definition, inclusion and exclusion criteria, strategies for recruitment, how the study intervention will be administered.
      • Methodology to minimize bias, such as randomization and blinding, as well as measures addressing protection of participants safety and consideration of any ethical issues. 
      • Statistical considerations, including how the sample size (number of participants) was determined and how the data will be analyzed.
      • Organization of the clinical trial.
    • Sponsor: The  Sponsor of a clinical trial is different from the investigator. The Sponsor manages or finances the clinical trial, but doesn’t conduct investigation. Pharmaceutical Industry Sponsors are common for newly developed therapies. 
    • Eligibility criteria: Listed in the protocol, these are the factors that allow someone to participate in a clinical trial. 
    • Exclusion criteria: These are the criteria that would not allow someone to participate. 
    • Control group: The control group is a subset of clinical trial participants who do not receive the investigational therapy so that their data can be compared to those who do. A control group can be given a placebo or continued on currently accepted therapies.  
    • Placebo: A placebo is an inactive drug, treatment, or therapy, that is given to a group participating in a clinical trial for the purpose of comparison to the group receiving the therapy. The Protocol document will outline whether placebos will be used; they are never used in studies where their use would be inappropriate, unethical, or harmful; in those cases, historical controls are often used. 
    • Informed consent: In clinical trials, informed consent is a complex, multi-stage process. The goal of the informed consent process is to provide sufficient information so that a potential participant can make an informed decision about whether or not to enroll in a study or to continue participation.  It requires:
      • Informing potential participants and/or their guardians thoroughly about:
        • The clinical trial protocol.
        • A participant’s responsibilities.
        • The responsibilities and limitations of the responsibilities of the clinical trial team and Sponsor.
      • Providing the information in easily understood language and in a way that potential participants and/or their guardians can understand.
        • Translating the information to a participant’s native language may be required if participants are not required to speak the primary language being used by the clinical trial team to join the trial.
      • Disclosing potential risks and benefits of the medical intervention under investigation.
      • Allowing potential participants and/or their guardians:
        • A significant amount of time to think about participating.
        • The ability to ask questions and discuss their concerns.
      • Obtaining a patient or their guardian’s voluntary agreement. 
      • NCATS Toolkit provides more information about the informed consent process in the following section: Giving Input on the Informed Consent Process.
    • An IRB or research ethics committee is composed of a group of people independent of the specific research who are tasked with reviewing proposed research plans and related documents before a study involving human participants can begin and then periodically (usually annually) for the study duration. 
      • Not all studies involving human participants must have an IRB review, however any studies involving medical interventions that will require FDA approval prior to marketing will. 
      • NCATS Toolkit provides more information about IRB and the review process in Serve on Review and Monitoring Boards: Institutional Review Boards.
  • Describe common benefits and risks of clinical trials.
    • Specific benefits and risks should be included in information a potential participant receives prior to joining a clinical trial. 
  • Provide links to more information. It can be difficult to cover everything someone may need to know in the depth that everyone may want to know it. Therefore it is helpful to provide links to other reliable resources to allow further exploration.  For example: 
    • How to Get Involved in Research (periodically updated) is a guide developed by the Genetic and Rare Diseases Information Center (GARD) for patients and patient groups and contains information about how to learn about research studies, how to find a research study for a rare disease, and patient registries. It is available as a webpage on the GARD website and includes a short video. The guide also can be printed.
    • Clinical Trials: What Patients Need to Know (periodically updated) is a webpage developed by the FDA and provides links to information about clinical trials. Links include information about the informed consent process, institutional review boards, and the differences between clinical trials and medical treatment.
    • From Molecules to Medicine: Clinical Research (2018) is one of the Global Genes web-based information rare toolkits. It provides basic information about clinical trials, how to find them, and what it means to participate in a trial in an easy to understand language and format.
    • ClinicalTrials.gov is a searchable online registry of recent and active clinical trials developed by the NIH through the National Library of Medicine. The website also includes information about how to find studies and learning about clinical trials in general.
    • Five Principles: Returning Genetic Testing Results to Research Participants (2014) is a paper from Genetic Alliance containing the five basic principles that the authors propose should be followed when returning research results to individual participants. 
• Develop an FAQ: An FAQ can be a webpage or in printed format that can be shared at conferences or in mailings.
  • Dispel any common myths. For example:
    • Participants in clinical trials are not guinea pigs; there are clear safety regulations.
    • Participants can withdraw from a clinical trial before its conclusion.
  • Address concerns that might be unique to your disease community.
  • Provide some of the general information and terminology considered above in “Choose what to include."
• Share the information: There are different ways to provide information, each potentially requiring different amounts of time and possibly reaching different people. You know those affected by your disease community best, so you will want to choose the method or combination of methods that will work best for your group. 
  • Post on your website. Depending on the current availability of clinical trials for your disease, you may wish to consider sharing general information about clinical trials by:
    • Highlighting internal webpages on the home page.
    • Dedicating a full tab section to information about clinical trials.
    • Including under a tab dedicated to Research or What You Can Do.
    • Sending emails with links to your webpages focused on research periodically to your group members or including in e-newsletters.
    • Posting the links on social media associated with your group. 
  • Hold an information webinar or virtual meeting. 
    • Include the experience of individuals or families who have participated in a trial.
    • Allow questions to be asked by those attending the webinar.
    • A video recording of the webinar can be posted on your website. 
  • Schedule sessions into your annual scientific or family conference.
  • Also use “snail” mail. Not everyone in your disease community has internet access, so doing a periodic mailing may help reach those who might not have easy access to websites and webinars
  • If there are dedicated clinics for your rare disease, provide FAQs, brochures, or infographics that can be picked up by patients or their families .

Alerting your disease community about currently available clinical trials can ease the burden for those wanting to participate. You may wish to:

• Dedicate a webpage to ongoing clinical trials for your disease. Most groups place this page under the Research tab or have it listed under several tabs.
• Explain whether the clinical trials have been vetted by your group or simply pulled in from ClinicalTrials.gov or another similar resource. 
• Highlight any clinical trials that were supported by your group’s effort.
• Clarify eligibility criteria as this is often the most difficult for those wanting to participate to understand.
• Organize the information about specific clinical trials so that it focuses on factors that may be important to members of your disease community when making an informed decision about whether to join the trial.  For example, 
  • Does the type of trial mean people could end up in a placebo or control group?
  • What phase is the clinical trial?
  • Will participants be responsible for any costs?
• Update the page regularly and Include the last-updated date in an easy-to-find place. 
  • Clinical trial status and contact information can change.
  • Develop an internal system where a staff member or volunteer regularly checks  the clinical trials listed on your page for any changes, especially in status (is it still accepting new participants) and contact information.

You can decrease the time it takes to recruit participants for clinical trials by alerting your disease community to upcoming and newly launched trials. However, you may want to establish a review process to determine which clinical trials your group will support. Including members of your Medical/Scientific Advisory Board or outside independent researchers and clinicians in your review process will strengthen your decision. If you decide to support recruitment, you can: 

• Email members when a new trial is added.
• Highlight new trials on the homepage of your website.
• Post on your group’s social media.
• Send alerts through “snail mail” or include in your printed newsletter if you have one.
• Identify members of your disease community who are most likely to meet eligibility criteria and are interested in joining clinical trials using your registry.

• Keep presentations balanced. Although you want your disease community to participate in clinical trials, you also want each person or family to make the right choice for their situation. Balanced information is key to retaining your patient community's trust.
• Set realistic expectations for any clinical trial. It is important for your disease community to understand that even interventions that make it to Phase 3 may not gain FDA approval. 
• Consider an opt-out for emails and social media about new clinical trials for those that do not want to participate. 
• Explore the websites of other groups to see how they provide general information about clinical trials as well as information about specific trials. 
• Reach out to the study coordinator and/or principal investigator if a trial pops up for your disease community that you were not expecting.