The Development of the Oncology Center of Excellence Patient-Friendly Language Glossary of Oncology Clinical Trial Terms

Abstract

Oncology clinical trials terms and definitions have become increasingly complex, which has led to shortcomings among research staff and healthcare providers in informing clinical trial participants with the study results and consenting procedures in simple language. Understanding oncology clinical trial terms is of critical importance to assist patients and caregivers in making cancer treatment decisions, including enrollment into clinical trials. The U.S. Food and Drug Administration’s (FDA) Oncology Center of Excellence (OCE) organized a physician and patient advocate-led focus group, with the primary goal of publishing a patient-centric public glossary of select cancer clinical trial terms for healthcare providers, patients, and caregivers. This commentary reports the results of the focus group sessions that gave FDA OCE valuable insights into how patients perceive clinical trial terms and how oncology clinical trial definitions can be improved to effectively communicate information to the patients to make better informed decisions about their treatment options.

This commentary reports the results of U.S. FDA focus group sessions that provided insight into how patients perceive clinical trial terms and how oncology clinical trial definitions can be improved to effectively communicate information to the patients to make better informed decisions about their treatment options.

Background

Cancer is a serious and often life-threatening illness with treatment options that can be complex. Effective communication between the patient and healthcare provider is critically important to assist patients in understanding the best course of action regarding cancer treatment options. Cancer clinical trials play an essential role in finding new ways to prevent or treat disease and can be an opportunity for patients to have access to novel investigational treatments that are not yet available to the public. Effectively conveying the process of enrollment, as well as details of the trial, influences patients’ with cancer decisions regarding whether to participate in a clinical trial.¹ It is important to recognize barriers to cancer clinical trial enrollment, such as complicated and difficult to understand terminology, that are sometimes overlooked by the treating physician. The use of patient-friendly language, such as words and phrases that are sensitive to the patient’s diagnosis and easy for patients to understand, can improve the existing communication barriers between the healthcare provider and patient, and potentially increase participation in clinical trials.²

Cancer clinical trial terminology is becoming increasingly complex and enrolling in a clinical trial can be a long and potentially complicated process. When enrolling in a clinical trial, patients are often presented with a complex and lengthy consent form that describes the clinical trial in detail, such as the investigational drug’s mechanism of action and potential safety concerns.³ Many of these forms may not be written in a patient-friendly manner due to the scientific nature of the terminology and frequent use of medical jargon. Additionally, the nomenclature used by healthcare providers or research coordinators when enrolling a patient into a clinical trial can be confusing because treatment regimens and clinical trial designs can be complex, making the goals and commitments to the trial unclear to patients.^4,5 Specifically, when a healthcare provider discusses the trial objectives and benefits and risks of an investigational drug in a clinical trial, misconceptions may lie in the nuanced nature of the clinical trial terminology and ultimately adversely impact the informed consent process. For instance, when efficacy endpoint terminology such as progression-free survival, overall survival, and overall response rate are discussed during the informed consent process, most patients find it confusing to delineate the differences.⁶ Thus, making it especially important to explain clinical trials words, such as efficacy endpoints, in a manner that is patient-friendly, so that patients can make the best treatment decisions for their particular cancer.

The Food and Drug Administration’s (FDA) Oncology Center of Excellence (OCE) recognized the need to ensure oncology clinical trial terms are clearly defined and more understandable to patients and their caregivers. To achieve this goal, OCE conducted a series of focus group sessions that provided valuable insights into how oncology clinical trial terms can be revised to effectively communicate information to patients, so that ultimately, it can help them make better informed decisions about their treatment options. This pilot project started in 2018, and over the last 3 years, the OCE has taken the initiative to engage and learn extensively from patients about their needs related to understanding oncology clinical trials and terminology. The project was started by holding an FDA public workshop entitled “Partners in Progress”, where common oncology endpoints, such as progression-free survival and overall response rate, were publicly discussed with regulators, patients, advocates, and industry.⁸ The workshop identified significant challenges that currently existed with patient-friendly language and built an initial framework which informed the future focus group meetings. This manuscript describes the expansion of this effort to create a glossary that encompasses a variety of clinical trial terms felt to be most important to patients.

Methods/Results

The OCE, in partnership with Cancer Support Community, developed a preliminary list of oncology clinical trial terminology that patients with cancer and patient advocates had identified as particularly difficult to understand when discussing potential participation in a clinical trial or reading an informed consent document. An initial survey that included a list of over 100 oncology clinical trial terms were administered to patients with cancer or those in remission from their cancer. The survey asked participants to choose which clinical trial terms they felt were most important and would like to see in the patient-friendly glossary. Based on the results of the survey among the 100 terms included in the survey 37 terms were identified and selected for the patient-friendly glossary. The chosen clinical trial terminology focused on endpoints, safety, eligibility criteria, statistical methods, clinical trial design, and regulatory science. FDA oncologists within the OCE began to draft preliminary definitions based on their expertise in oncology clinical trial design and knowledge from reviewing protocols and informed consent forms at the FDA.

Once initial patient-friendly definitions of the 37 clinical trial terms were drafted by the OCE, a focus group consisting of FDA physicians, patients, and patient advocates was formed to further refine the definitions. A total of 4 focus group meetings occurred virtually over a period of 4 months. Prior to convening each focus group meeting, a written survey was sent out to participants. Each survey contained 20 terms with 3 choices of definitions; a definition developed by OCE, a third-party definition (definition from NCI oncology glossary or cancer.net) and “other” write-in option. All focus group members were required to participate in the survey. Definitions were considered final if focus groups had 75% or greater concurrence on a definition. Definitions with less than 75% concurrence on the written surveys were further discussed during focus group meetings. Focus groups discussed the clinical trial terms that did not reach concurrence in written surveys in detail to arrive at definitions felt to be the most patient-friendly and accurate by the majority of the convened focus group. Upon completion of the 4 focus group discussions, a complete and final list of oncology clinical trial terms and definitions was developed and published on the OCE’s website.⁷

Discussion/Insights

In an era when clinical trial terminology is increasingly complex, translating medical jargon and definitions into language that is both patient-friendly and accurate is needed. By building this patient-friendly glossary for select oncology terms used in clinical trials, we addressed select words and phrases that patients with cancer identified as particularly difficult to understand when discussing study results with their doctor or reading an informed consent form. By working together with patients, healthcare providers and advocates to build the glossary terms, we were able to choose words that patients felt were most challenging to understand and to address gaps in communication. It is our hope that by providing more patient-friend definitions to common trial terminology, we may positively impact clinical trial participation, adherence to a protocol, and more informed shared decision making when weighing risks and benefits of approved cancer treatment options.

The focus group included patients with different experiences in order to obtain a wide range of perspectives. No surprisingly, the understanding of oncology clinical trial terminology varied among the individual participants, as well as their perspective on what would be a more appropriate patient-friendly definition. For example, when defining the word “maximum tolerated dose (MTD)”, physicians in the group used technical words such as “adverse event” to describe the unintended side effects from a dose finding study. Patients on the other hand, preferred defining MTD using more patient-friendly language such as “the highest dose of a drug or treatment that does not cause unacceptable side effects.” Interestingly, this raised valid discussion points that unacceptable levels of side effects may be different from person to person. Additionally, clinical trial efficacy endpoint terminology was a challenge to define within the focus group highlighting the fact that overall survival, progression-free survival, disease-free survival, overall response rate, and time to treatment discontinuation are nuanced. However, the focus group did achieve concurrence and arrived at clinical trial terms that were felt to be more understandable to patients.

The OCE’s patient-friendly language glossary strives to provide healthcare providers, patients, and caregivers a resource to better understand nuanced language used in cancer clinical trials. Although many stakeholders were involved in generating the definitions, there remain trial terms that were not identified during the focus groups and could be addressed in future focus groups. To continue to mitigate the barriers of communicating oncology clinical trial terminology into patient-friendly language, we will continue to engage with patients, caregivers and healthcare providers to further our commitment to expand the patient-friendly language glossary. Future opportunities to optimally inform patients may include graphics and diagrams on the website to clarify complex endpoint terminology and expanding the oncology patient-friendly glossary to include increasingly important and scientifically complex topics such as diagnostic biomarkers, including next generation sequencing terminology.

Conclusion

A patient-friendly glossary published by the FDA Oncology Center of Excellence (Table 1) is now publicly available to aid patients in understanding complex clinical trial terminology. The oncology clinical trial terms and definitions used in the glossary were generated from sustained multi-stakeholder engagement that generated rich feedback and discussions through patient workshops, surveys, and focus groups. We hope that this patient-friendly glossary will help better inform discussions and decision-making surrounding enrollment and participation clinical trials, as well as facilitate shared decision making between patients and healthcare providers when discussing trial results that inform the risks and benefits of FDA approved therapeutic options. The OCE is committed to making oncology clinical trial terminology more understandable for patients, and we will continue to work with healthcare providers, patients, and their caregivers to bridge gaps in communication to advance informed oncology clinical trial participation and therapeutic decision making.

Table 1.

FDA OCE’s patient-friendly glossary.

Active comparator arm: The group of patients that is given an effective (or potentially effective) treatment as opposed to a placebo comparator (“sugar pill”) in a clinical trial, which is then compared to the experimental arm. Also called Active Control.

Adverse event: An occurrence that has a negative impact on the health or well-being of a patient in a clinical trial during or within a certain length of time after the study.

Blinded study: A type of study in which the patients (single-blinded) or both the patients and their doctors (double-blinded) do not know which drug or treatment is being given.

Cancer recurrence: Cancer that has come back, usually after a period of time during which the cancer could not be detected.

Compassionate use: A way for patients with a serious disease or condition who have no other treatment options to gain access to an investigational drug that has not been FDA approved for that disease of condition. Also referred to as expanded access.

Disease free survival (DFS): The average length of time from the start of treatment that patients remain cancer free.

Dose escalation study: A type of study where enrolled patients receive different doses of the drug or investigational agent to determine the recommended phase II dose (RP2D).

Dose limiting toxicities: Describes side effects of a treatment that are serious enough to prevent an increase in dose of that treatment.

Drug holiday: When a patient does not take a medication for a specified period. Can be temporary and last anywhere from a few days to months. Also referred to as a medication vacation.

Eligibility criteria: A set of characteristics defined by the research investigator based on safety and efficacy of the treatment, used to determine whether a patient can enroll on a clinical trial. These characteristics identify a specific patient population and may be different from trial to trial.

Endpoint: In clinical trials, an outcome that can be measured objectively to assess whether a treatment worked.

Exclusion criteria: A type of eligibility criteria. These are a set of characteristics used to determine when a patient cannot participate in a clinical trial. An example would be “active or uncontrolled infections”, and “anti-cancer therapy within a specified period of time”.

First-line therapy: The first treatment given for a disease. It is often part of a standard set of treatments, such as surgery followed by chemotherapy and radiation. Also called induction therapy, primary therapy and primary treatment.

Generic drug: A drug manufactured to be the same as an already approved brand-name drug. It contains the same active ingredient(s), dosage, route of administration, and same safety profile.

Inclusion criteria: Inclusion criteria specify the characteristics required for clinical trial entry. Characteristics required for entry into a clinical trial may include “men and women between the ages of 18 and 75”, and “metastatic triple negative breast cancer”.

Informed consent: A process in which patients are given important information, including possible risks and benefits, of a treatment, genetic testing or a clinical trial. This helps patients decide if they want to take part in the clinical trial.

Institutional Review Board (IRB): A group of scientists, doctors, clergy, and patient advocates that reviews and approves the detailed plan for a clinical trial.

In vitro drug testing: Evaluation of a drug in a laboratory within a test tube or laboratory dish.

In vivo drug testing: Evaluation of a drug in a living organism, such as an animal or human body, and not in a test tube or laboratory dish.

Off label: The use of a drug for a condition that does not have an FDA approved indication

Open-label study: A type of study in which both the doctors and the patients are aware of the treatment that is being given.

Orphan drug: A drug used to treat, prevent, or diagnose an orphan disease. An orphan disease is a rare disease or condition that affects fewer than 200,000 people in the US.

Overall response rate (or Objective response rate or ORR): The percentage of patients whose cancer shrinks or disappears after treatment.

Overall survival (OS): The average length of time patients are alive after the start of treatment.

Placebo: An inactive drug or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or other treatment are compared to the effects of the placebo (“sugar pill”).

Progression-free survival (PFS): The average length of time after the start of treatment in which a person is alive, and their cancer does not grow or spread.

Protocol: Detailed plan of how a new drug will be studied. In clinical trials, it states what the study will do, how it will be done, and why it is being done.

Randomization: The process by which participants in clinical trials are assigned (by chance) to separate groups that are given different treatments.

Recommended phase II dose (RP2D): The dose of a drug or drug combination that was identified in a Phase 1 study (dose finding study) that was identified for continued study in future clinical trials.

Response Evaluation Criteria in Solid Tumors (RECIST): A standard way to measure how well a patient responds to treatment. It is based on whether tumors shrink, stay the same, get bigger, or spread to a new part of the body.

Risk-benefit ratio: An analysis that determines the potential harm (or risk) vs the potential advantages (or benefit) of a treatment.

Schedule of assessments: A timeline that contains all activities, such as imaging, blood work and doctor visits, that will be done while enrolled in a clinical trial.

Standard of care: Treatment for a disease that is accepted and widely used by doctors.

Subject: A person participating in a clinical trial.

Time to treatment discontinuation (TTD): The amount of time from when this treatment was started to when it was stopped.

Treatment arm or experimental arm: The group of patients that are given the new treatment that is under evaluation.

Wash-out: A required period of time when a patient is not undergoing any treatment (chemotherapy or cancer drug) before a patient enters a clinical trial.