Outreach

Helping potential participants understand their rights prior to beginning the informed consent process can help mitigate any concerns that may jeopardize participation. It can be helpful to provide information about the informed consent process before a clinical trial is ready to recruit. Your knowledge of the informed consent process together with your knowledge of your disease community can help you determine the best approach to ensure the process reaches its goal of informed consent. 

• Provide general information about clinical trials and informed consent on your website.
• Explain possible future benefits of studies that may not provide immediate benefit to participants, for example what the study hopes to discover, mitigate, or develop.
• Hold a webinar about informed consent and make it available to those who can’t attend. 
• Bring in speakers at an upcoming conference who can talk about the informed consent process.
• Develop InfoGraphs or pamphlets that can be downloaded from your website or mailed to members who may not have easy internet access.
• Post links to relevant information, events, or webinars provided by large umbrella organizations like NORD, Global Genes, and FasterCures.

Communicate with Sponsor

You will know the strengths, limitations, needs, and desires of the target population for a clinical trial better than the Sponsor. Now that you understand the informed consent process and obligations of different settings, you can provide insight into elements of the informed consent process that can be proactively addressed to minimize concerns and increase informed participation. You may discuss:

• Reading level appropriate for target participants and/or guardians.
• Language requirements, for example, does a significant part of the population speak a language other than English.
• Potential concerns of the target participants. For example, participants may be concerned about having to discontinue current treatment or it may be important for them to know if they can still go to school or work during the clinical trial.
• Predictable acceptability to target participant population if individual results may not be returned. 
• Clearness of the legal and ethical obligations depending on the setting of research.
• Expectations of clinical care.
• Terminology that the target participants or their guardians may or may not understand.

Tips for Success

• Know what decisions you want to influence and whether the questions you are asking will help you reach that goal. 
• Explore whether there are other ways that are less demanding on time and resources to achieve your goals, such as focus groups or interviews.
• Develop collaborations with a shared understanding of the purpose and use of information generated.
• Understand the significance of using sound science to develop and analyze patient preference studies.
• A clear understanding of objectives translates into choosing the appropriate methodologies to achieve those objectives.
• Engage the FDA throughout the process.
• Remember patient and caregiver preferences may change over time as new therapies become available.
• Read Key Considerations in Developing & Integrating Patient Perspectives in Drug Development: Examination of the Duchenne Case Study (2016), a report providing information to help you decide if and when your group wants to conduct a patient preference study. The report also provides more details about the different types of studies and analyses.
• Review Benefit Risk Bootcamp (2014), an overview of sessions from an FasterCures event that describes effective participation in benefit-risk assessment. Descriptions and slide presentations from each session are available. Topics discussed include understanding benefit-risk assessment, common methods used, and key FDA programs.

Lead or Support

Patient preference studies can be performed by your group, other patient groups, industry, academia, and even the FDA, as is the case with Patient-Focused Drug Development (PFDD) Public Meetings. Depending on the timing and reasoning behind a patient preference study, it may be most helpful to form a collaboration. Remember that the objective of a patient preference study is to gain perspectives that are representative of the entire patient population, so working with other groups and reaching out to patients that may not belong to any group can increase the impact of the study. When you are deciding whether to perform the study alone, or take the lead or play a supporting role in a collaborative effort, you may wish to consider a number of factors.

• Cost of performing a study:
  • Study costs may range from $100,000 to $400,000 and up.
• Staff time needed for the duration of the study:
  • Studies may take from 6 to 9 months from start to finish.
• Requirement of external expertise to design and analyze study:
  • Large industry partners may have expertise among their staff.
  • Academic partners can offer experience, scientific rigor, and credentials, as well as a knowledge within a specific disease area.
• Outreach experience to include patients outside group membership.
• Historical participation of membership in similar surveys.

Overview

Capturing data on how patients perceive potential risks and benefits of new treatments can inform therapy development and the U.S. Food and Drug Administration (FDA) marketing review process. Patient preference studies, also known as patient-centered benefit-risk studies, can help identify what is most important to patients, particularly when assessing benefits and risks are challenging.

Advantages

A patient preference study is a way to collect and analyze patient and caregiver preferences concerning risks they are willing to accept for a specified benefit provided by a treatment. In fact, patient and caregiver preferences can differ greatly from what clinicians and researchers might expect, especially in the rare disease community. Although performing patient preference studies during each stage of therapy development has become more common, the FDA does not require Sponsors to include these studies. Therefore, you may wish to educate research and industry partners about the advantages of patient preference studies. The data from patient preference studies can:

• Characterize the burden of disease, unmet medical needs, patient perspective on benefit-risk, and diversity of preferences in the patient population:
  • Identify what is most important to patients.
  • Understand the maximum risk and/or burden patients will accept for different benefits.
  • Learn how patients may compare benefits and risks between 2 therapy options.
  • Determine whether preferences differ based on demographics or geographical location.
  • Investigate other, differentiating factors that may affect patient preferences, such as severity of symptoms or stage of disease.
• Influence the design of clinical trials: 
  • Develop endpoints that matter to patients.
  • Select target populations within the patient group.
  • Reveal confounding factors that may require stratification of participants during analysis, for example, participants may be stratified by age or disease stage in order to best determine effectiveness and safety of treatment.
  • Develop meaningful effect sizes for endpoints based on patient and caregiver preferences. You can learn more about Clinical Outcome Assessments (COAs) in NCATS Toolkit section on Help Industry With Clinical Trial Design.
  • Determine how to promote patient participation to make certain enough participants enroll. 
  • Uncover factors that may affect a participant’s decision to discontinue participation in a clinical trial.
• Impact the FDA marketing review process:
  • Qualified COAs developed through the inclusion of patient preferences can be presented to FDA for consideration during the clinical trial and marketing review process. 
  • Benefit-risk of therapies targeting unmet medical needs may be assessed more tolerantly by FDA.
  • Patient perspective of benefit-risk determined through scientifically performed patient preference studies will be considered by FDA during the marketing review process.
• Provide patients with information important to their treatment decision-making process after a therapy receives FDA marketing approval.
  • COAs may be used in labeling the therapy to allow better understanding of benefits and risks of use.

Timing

The timing of patient preference studies depends on the stage of therapy development you are hoping to influence. 

• Early patient preference studies focused on understanding unmet medical needs, burden of disease, and general patient benefit-risk perspectives can provide crucial information during the therapy discovery phase to academic and industry researchers.
  • Influence symptoms to be targeted for treatment development.
  • Attract interest of academic and industry researchers.
  • Determine priority of therapies in early development from a patient perspective.
• In the preclinical phase of therapy development, when researchers have completed initial analyses of the possible benefit-risk of a potential therapy, patient preference studies can obtain information about more specific preferences and can use this data to develop clear COAs.
  • Ask about more specific benefit-risk scenarios that may influence clinical trial design and patient subpopulations to target for enrollment.
  • Develop a COA or choose one that already exists. You can learn more about COAs in NCATS Toolkit section on Help Industry with Clinical Trial Design.
  • Determine information that may be important to patients during their decision process of whether or not to enter a specific clinical trial. 
• During Phase 2 and 3 clinical trials, patient preference studies can be focused on actual benefits and risks seen among trial participants.
  •  The data from studies performed now can be submitted to the FDA to be included in the marketing review process.
• After therapy approval, patient preference studies can be used to detect any difference between stated preferences (what a person believes they will choose) and revealed preferences (what a person actually chooses).

Engage with the FDA

Groups that have successfully traveled the therapy development path advise engaging with the FDA early in the process of developing and conducting patient preference studies. Establishing an ongoing conversation with the FDA can make certain you are asking your disease community the questions that are significant to the FDA throughout the clinical trial and marketing review process. 

• Patient Affairs , available at +1-301-796-8460, works with patients and patient advocates to involve patients more effectively in regulatory decisions related to therapy safety and approval. The Patient Affairs Staff are the best resource to understand who to contact at the FDA and when. 
  • For Patients , focuses on topics that can help you learn more about the different programs and processes of the FDA, as well as upcoming public workshops and meetings. 
• Medical Device Innovation Consortium (MDIC) Patient Centered Benefit-Risk Project Report (2015) emphasizes the opportunity to work with FDA Center for Devices and Radiological Health (CDRH) staff from early stages of medical device development. The report covers the value of patient-preference information and considerations that should be made when using this information.  The Report has elements that cross over to drug and biologic development. 
• FDA-led PFDD Public Meetings ran from 2012 to 2017 as an effort to collect the patient perspective on the burden of their specific disease and unmet medical needs. Meetings continue to be held periodically but tend to be focused on wider public health issues, such as chronic pain and opioid use disorder. You can learn more about the FDA-led PFDD Meetings using the following resources:
  • FDA-led Patient-Focused Drug Development (PFDD) Public Meetings describes the purpose of the meetings and lists the 24 selected disease areas as well as links to the agenda, slides, recordings, transcripts, and meeting summaries.
  • Enhancing Benefit-Risk Assessment in Regulatory Decision-Making provides history of the development of FDA-led PFDD meetings and the integration of patient preference into the benefit-risk assessment by the FDA during clinical trial and marketing review process through links to the legislation. 
  • NCATS Toolkit also has a section providing more information about the option of holding Externally-Led PFDD Meetings.

Securing an Invitation

FDA regulators are increasingly interested in having patients and patient group representatives participate in these early discussions, but the Sponsor is the one who will invite you to a pre-IND meeting. It is your job to make certain the Sponsor is aware of the benefits of your participation. Studies are often designed with hard data and statistical measures in mind, but this approach may not produce results that the patients and caregivers find valuable. Your participation in pre-IND meeting can ensure the FDA that the study objectives are designed with the needs of the patient community in mind.  

Participation by your group representatives in initial meetings between the Sponsor and the FDA can reduce therapy time to market by:

• Ensuring that studies are designed to provide useful information.
• Enhancing the understanding of data proposed to be gathered by clinical trial.
• Providing a platform for the patient voice.
• Creating or further growing a relationship between your group and the FDA.
• Minimizing clinical holds on therapy development (an order issued by FDA to delay or suspend an ongoing trial/investigation).

Learn about Pre-IND Meetings

A pre-IND meeting is a Type B FDA meeting which occurs early in the therapy development process to help to guide trial strategies. These meetings can help facilitate faster therapy approval processes. Pre-IND meetings greatly increase the likelihood of a program’s success by allowing concerns to be addressed early in the trial process. Pre-IND meetings are also a great opportunity to build a relationship with the FDA, minimize costs, and identify preclinical studies that have already been conducted. They are especially important when the therapy is intended to treat a serious or life-threatening disease.  

Note: A pre-IND meeting is for drug development. A pre-BLA meeting is for licensing of biologics. For device development, the process, when required  is called “pre-submission”, but is very similar. 

• Understand the purpose of pre-IND meetings:
  • Identify supporting preclinical trials. 
    • A preclinical trial is a trial that tests the proposed therapy in animal or cell models. 
    • A preclinical study is required before clinical trials in humans can be started. 
    • By identifying these studies, you and the therapy Sponsor can gain access to feasibility, testing, and safety data that has already been generated.
  • Identify possible designations and development and review statuses that may accelerate or enhance the clinical trial or marketing review process. The FDA provides information about each of the available programs:
    • Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review  
    • Developing Products for Rare Diseases & Conditions
• Consider the main goals of a pre-IND meeting:
  • Reduce time to market.
  • Address novel qualities of application.
  • Provide guidance to industry/small business Sponsors new to process.
• Be aware of recurrent problems at pre-IND meetings, especially problems that your group may be able to address prior to the meeting. Identified problems include:
  • Inadequate chemical, manufacturing, and controls (CMC) information .
  • Insufficient preclinical support.
  • Unacceptable clinical trial design.
  • Noncompliance with Good Clinical Practices (GCPs ).
  • Lack of information on selection of dosage.
• Review the list of frequently asked questions the FDA has prepared for Sponsors about pre-IND meetings. Although written for small business and industry, the information answers many of the questions you may be asking as well: Small Business and Industry Assistance: Frequently Asked Questions on the Pre-Investigational New Drug (IND) Meeting (updated periodically).