The Patient Voice in Designing Clinical Trials… Advocates can Help

By: Mary Lou Smith, JD, MBA and Elda Railey

There’s a lot of buzz these days about Precision Medicine, the Moonshot, new targeted therapies and immunotherapies but one thing has not changed…. a cancer treatment’s efficacy and safety must be tested in a clinical trial. Historically only 3-5% of adult cancer patients participate in clinical trials. Genomic medicine creates even more challenges for the clinical trial enterprise. When designing the trial, researchers need to determine what a patient will and will not be willing to agree to. These factors can include:

  • The importance of the question being studied to the potential participants
  • The burden the requirements of the trial will place on the patients and their caregivers
  • Appropriateness of the eligibility criteria to that person’s situation

Potential participants may also react to specific design elements such as:

  • Requiring a drug holiday even when the treatment is working
  • Randomization of participants
  • The use of a placebo when no standard of care exists to be tested

Gathering input on clinical trial design is like voting in Chicago you need to do it early and often. Advocates can provide strategies to make difficult design elements more acceptable, and suggest ways of talking about/explaining those elements that are understandable and reasonable. We learned the value of early patient and advocate input when we conducted focus groups to inform the design of what became the TAILORx Trial. The input from the patient and advocate focus groups didn’t change the basic question but it did change the design of the trial. Originally all the participants would be randomized to receive the Oncotype DX test or not. Given the high patient interest in the test, in the final design all the participants received the test. The advocates and patients were concerned about randomization to treatment and in the final design only participants with an intermediate score on the test would be randomized to receive chemotherapy or not. The result was a trial that accrued over 10,000 women with early stage breast cancer and has provided results that have changed clinical practice.

Advocates have also been involved in the NCI MATCH Trial. During review of the trial design, advocates were concerned about a specific design element and looked at a different method of gathering input – keypad response technology. The investigators were recommending a drug holiday for patients with advanced or metastatic cancer whose disease had responded or been stable after six months of treatment with an experimental drug. Advocates were concerned that patients would disenroll rather than be taken off a treatment that was providing benefit. We used keypad response technology and surveyed advocates and members of ECOG, the sponsoring cooperative group. We found there was uniform discomfort from the surveyed groups with the drug holiday. With the information gathered from these surveys, the drug holiday requirement was not included in the protocol.

Another way of getting early input is to go to an advocate organization and ask them what questions are important to their patient constituents. We asked the program directors of Gilda’s Club (now Cancer Support Community) what side effects were most bothersome to patients and why. We gathered this information by phone discussions. These lead discussions provided us with a list of side effects and detailed reasons why the patients found the symptoms bothersome. One of the identified symptoms was the arthralgias from treatment with aromatase inhibitors (AIs). The results of these discussions with the program directors were presented to the ECOG Symptom Management Committee. ECOG now has a trial studying AIs.

Including the patient voice is one way of respecting the patient and forging a bond with an advocate organization. Engaging the advocate organization could also be helpful in getting the word out about the trial and letting patients know their voices were heard and acted upon.

The value of early input for sponsors is a huge cost savings. It is easier and less costly to make changes before the trial is activated. Forty percent of NCTN trials close early usually because of slow accrual. This is a waste of time, money and most importantly patient data. The data from the participation of these patients is lost to research and could be seen as a breach of trust. Advocates, patient organizations, and the clinical research community need to work together to advance the science for patient benefit…. not just to answer scientific questions.

About the Author:

Mary Lou Smith, JD, MBA and Elda Railey

Mary Lou Smith, JD, MBA and Elda Railey are co-founders of Research Advocacy Network ( Mary Lou serves as co-chair of the Translational Breast Cancer Research Consortium patient advocate committee, chair of the ECOG-ACRIN patient representative committee and many other capacities.  She can be reached via email at

Elda serves as a patient advocate on the SWOG Breast Cancer Committee, the UT Southwestern/ MD Anderson Lung Cancer SPORE and chairs the Patient Advisory committee for ASCO’s CancerLinQ. She can be reached via email at

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