clinical trials: patients at the center

special editorial submitted by champion steward partner janssen pharmaceutical companies of johnson & johnson

Good health for mothers and babies in the womb creates the foundation for a vibrant childhood and future. Very rarely, despite maintaining good health, a mother and developing baby can have different blood types that are not compatible, putting them at risk for a disorder known as hemolytic disease of the fetus and newborn (HDFN), which affects 3 to 80 in 100,000 patients per year in the U.S.1 In HDFN, a mother’s immune system identifies the fetal red blood cells as “foreign” and mounts a response that can cause serious health complications for the fetus.

Scientists are developing new treatments to be safer, more effective, and less intrusive than the current standard of care for the most severe forms of HDFN. These investigational treatments harness the latest knowledge of how the immune system works and employ new antibody therapy technology. For example, Janssen’s Autoantibody Pathway scientists are researching antibody-based treatment as a potential therapy for pregnant women who have a high risk of severe HDFN. What does it mean to participate in a clinical trial? What’s involved? for remote visits as part of trial participation, but also want to know what would be involved.

Equipped with this knowledge, we try to adapt study protocols and address needs as best we can. For example, in one study, patient focus groups helped Janssen determine if patients’ trial tools -- such as a symptom diary -- were user friendly enough to capture important study information. Thoughtful adaptations and explanations can help reduce patients’ stress and burdens while improving trial enrollments and increasing participant retention.

Patients at the Center: Trials and Innovation

Janssen is driven by a relentless dissatisfaction with the status quo, working to improve existing treatment options for patients and address unmet patient need. Central to our ability to study immune disease and innovate better solutions is our relationship with patients and physicians and the belief that close communication is important to reflect the patient voice when developing clinical trials. We want to learn from patients and their caregivers what will help or hinder participation in our studies so that we can modify our trial protocols accordingly. By talking to patients, we learn about the need to explain technical terms, or, when English is not a native language, the importance of having a translator available. By talking with patients, we’ve learned that office visits might be hard for someone using a wheelchair or that drug packaging might be difficult to open for someone with arthritis. We’ve learned that patients are interested in the potential

Clinical Trials

Drug intervention clinical trials are rigorous studies, done with volunteers, that generate the information and scientific data needed by the U.S. Food and Drug Administration (FDA) to consider the benefits and risks of a candidate drug and then decide if it is safe and effective for patients. Nearly 32,000 trials are recruiting participants or are underway today in the United States.2

Trial Phases

The testing of an investigational drug in humans is done in a progressive series of clinical trials, defined in the United States by the FDA as four phases with distinct enrollment sizes, durations and purposes: • Phase 1 studies examine a drug’s safety and dosing in a very small number of healthy volunteers or people with the disease and can last a few months. This phase starts with very small doses of the study drug and watches patients closely to understand any side effects, as well as how the body processes, metabolizes and excretes the drug. • Phase 2 trials examine the drug’s efficacy (or effectiveness) and side effects in groups as large as several hundred people with the disease. These studies can last several months to up to two years, depending on the condition being studied. • Phase 3 studies are designed to determine how effective the drug is compared to what’s currently available to treat the illness or condition. These studies examine drug efficacy and adverse events in hundreds to thousands of people with the disease or condition, and can last for many months or even multiple years. These studies include enough patients that scientists can evaluate results in subpopulations of patients, such as based on their disease markers or status, demographics or different drug dosing. • For some FDA-approved drugs, Phase 4 trials continue to examine the drug’s safety and efficacy in patient populations as large as several thousand. These trials can help detect unexpected adverse events.

Of note, the FDA permits different enrollment targets when the disease is considered. For example, advanced trials of heart disease therapies can enroll thousands of patients. In contrast, those for a rare or “Orphan” disease like HDFN may enroll about two dozen patients.

The study protocol or plan

Every study has a protocol or plan that outlines how the study will be conducted. This includes how many participants are needed to ensure the target patient population is well represented to generate enough data to permit rigorous statistical

analyses required to prove the results are authentic and not just a coincidence. The protocol also outlines the trial duration and the type and schedule of any dosing, additional treatments, procedures and tests. Notably, the plan also states how information and data about the participants and their experience will be collected, assessed and protected.

Defining Success

All clinical trials collect data about the drug’s effectiveness and safety, as well as the participants’ health. Study plans prioritize such endpoints into primary, secondary and, sometimes, tertiary or exploratory. Primary endpoints collect information to support the main patient outcomes that demonstrate the drug’s efficacy or safety. For a new medicine to be approved by the FDA, it’s not enough to be safe and effective; these studies also demonstrate that the medicine is better than what’s currently available to treat the disease or condition.

Defining Common Study Terminology

Let’s do a little translating. Here’s a common description of a study:

“A Phase 3, randomized, double-blind study.” The study phases are fully described above. Randomized refers to the random method of assigning patients to a specific treatment within the study. Since it’s important that study results be as objective as possible, neither the physician nor the patient knows which treatment the patient receives. This is referred to as a “double-blind.”

Protecting Patients

Before any U.S. clinical trial begins, the FDA requires that an independent institutional review board (IRB) must review and approve the study plan to make sure it meets ethical and safety standards. The IRB checks to see if the risks involved in the study are minimized and reasonable in comparison to its potential benefits. The strict oversight of the IRB includes its review of the process and forms by which people receive and understand trial information and provide their informed consent to enroll in a study. The informed consent process is meant to protect participants and make sure they grasp the trial’s risks and potential benefits. For a new medicine to be approved by the FDA, it’s not enough to be safe and effective; these studies also demonstrate that the medicine is better than what’s currently available to treat the disease or condition.

Should You Participate in a Trial?

Participating in a trial is a highly personal decision, and one that should be made after carefully reviewing the information you receive about the study plan and what to expect. If you choose to enroll in a clinical trial, you will be making medical history! Your participation will contribute to understanding the risks and benefits of a drug that has the potential to change someone’s life for the better.

To find a trial you might consider, visit clinicaltrials.gov. All clinical trials that are planning to or are already enrolling patients are listed at this site. In addition, some pharmaceutical companies have searchable websites of the trials they are planning or conducting. Janssen’s Global Trial Finder is on the company website, for example. If you think you might be

interested in participating in a clinical trial, you should start by talking to your doctor. Clinicaltrials.gov suggests that you ask these primary questions: • Are there clinical trials available for the disease I have? • 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 [randomization])? • 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? • Where would I have to go to participate, and how often will I have to visit the hospital or clinic? • How long will the study last? • What type of long-term follow-up care is part of this trial? • Will the results of the study be provided to me? • Who will oversee my medical care while I am participating in the trial? Medical advances are made possible through the commitment and collaboration of so many: scientists, physicians, nurses, and social workers. But central to all is the participation of patients. To learn more about clinical trials go to ResearchIncludesMe.com or learn more about Janssen's HDFN trial here: https:// unityhdfn.com/.

References 1. Ling, L., Yu, D., Gleeson, C. D., & Moise, K. (2021). 968 Estimation of hemolytic disease of the newborn in the United States from 1996-2010. American Journal of Obstetrics and Gynecology, 224(2), S600–S601. https://doi.org/10.1016/j. ajog.2020.12.993. Accessed March 2021.

2. Clinicaltrials.gov. Recruiting or Active trials United States. Available at: https://clinicaltrials. gov/ct2/results/map?recrs=ad&map. Accessed March 4, 2021.