Considerations For The Ethical Use Of Patients In Clinical Trials

By Ed Miseta, Chief Editor, Clinical Leader

Linda Strause, PhD, is passionate about the ethical treatment of patients. Her interest in the ethics surrounding human subjects stems out of her work with the San Diego Hospice. She ultimately served as the chair of the San Diego Hospice and Institute of Palliative Medicine IRB for 15 years. While that experience provided her with a close look into the treatment of patients, her interest in the subject quickly became more personal when she learned her husband had developed inoperable brain cancer.  

“I suddenly found myself wanting to get more involved in clinical trials simply for the sake of my spouse,” she says. “It’s an experience that affects you in a very profound way. Having gone through the experience, you suddenly find yourself wanting to help others who are dealing with the same tragic situation that you had to go through.”

In this Women in Bio profile article, Strause shares her views on the treatment and protection of human subjects, particularly terminally ill patients, taking part in clinical trials.     

Ed Miseta: Tell us about your job and what you do.

Linda Strause: Throughout my career I have always had an interest in doing all I could to contribute to the patient community and improving their quality of life. So as a consultant to the life science industry I primarily work with sponsors and CROs to make clinical trials more efficient. I also attempt to make those trials friendlier to the patients taking part in them. I feel anything we can do to make trials more centered on the lives of the patients, the better off we will be as an industry.

Miseta: What factors must sponsors consider when working with human subjects?

Strause: The protection of human subjects is an area at which we all need to take a closer look. That would start with looking at the principles laid out by the Belmont Report on the ethical guidelines for human subjects. The report, issued in 1978, noted three fundamental ethical principles for using any human subjects for research purposes. The principles are 1) respect for persons and protecting their autonomy, 2) beneficence, or the philosophy of do no harm, and 3) justice, or ensuring reasonable, non-exploitive, and well-considered procedures are administered fairly.

The issue of autonomy is probably the most difficult to deal with when the individual is facing a life-threatening disease. The main question comes down to this: If a person is dying, are they autonomous? Does a person in that situation have the freedom to act independently?

When I was chair of the IRB at San Diego Hospice, some thought that it was incongruous to think that terminally ill patients were autonomous. If a patient entered a clinical trial, they were obviously hoping for a cure. That hope, in and of itself, somehow reversed the concept of autonomy. In other words, you could not be completely autonomous if you wanted to be cured so badly that it was the only thing you cared about.

Miseta: Do you believe that?

Strause: No, I do not. In fact, I have made presentations to our industry on the concept of the Evolution of Hope, my belief that hope changes over time. In the beginning a patient might hope for a cure, but over time they transition through a journey. For example, if someone is diagnosed with incurable brain cancer, they may transition from hoping for more time, to hoping for a better quality of life, to simply hoping for more comfort. Eventually they may simply hope for some dignity in death. Patients do not lose hope. There is simply a change in what they are hoping for.  

Miseta: How does that impact the conduct of clinical trials on terminally ill patients?   

Strause: That is a good question. When we conduct trials on terminally ill patients, or patients facing life-threatening diseases, we have to allow them the freedom to hope. At the same time, we have to respect their requirement for autonomy, beneficence, and justice. Individuals who are dying do have the right to participate in clinical trials. That is the principle of justice – everybody has that right. Weighing the potential risks and the potential benefits is not just a curative approach. It can also be a palliative approach.   

As far as autonomy, I used to always say that there are patients dying to participate in clinical research. I honestly believe that no one is more altruistic than a person who has come to accept their own mortality. I think we do not do a very good job of teaching people that they are not immortal. Death is the only way out of this world, and accepting and understanding that is something we need to consider when designing clinical trials and obtaining patient consent. The dialogue has to change. The physician, investigator, and study coordinator have to understand the state of mind of the patient and family and/or caregiver, and the feeling of hope that comes with an incurable diagnosis.

Miseta: Where has most of the clinical focus been for sponsors?

Strause: Primarily the later stages. I have one client that is performing a stage 2 trial for colon cancer. Most cancer trials today are still for stage 3 and stage 4 diseases, because the FDA wants overall survival of patients as an endpoint. You can’t really take a stage 1 cancer patient and have overall survival as an endpoint. You would be running clinical trials forever.

Miseta: Will pharma be able to change their approach to getting these terminal patients more involved?

Strause: We hear a lot of talk today about patient centricity. With terminal patients the approach doesn’t need to be different, it just needs to have that perspective of hope, altruism, and other characteristics that are common to terminally ill patients. I speak with a lot of terminally ill patients and I lived with one for two years. There are certain characteristics you take on once you accept your own mortality, and they can be different for all people. I think our industry needs to better understand that the culture, if you will, of individuals facing life-threatening diseases. If we do not consider those patient characteristics when planning our trials, we are doing those patients a great disservice.

Unfortunately this industry is one that is very slow to change by I do see change. We are now designing protocols with input from key opinion leaders and by getting patients more involved than we have in the past. I have found that many of my clients are doing so. But I’m sure there are still medical directors in some companies writing it themselves.      

Miseta: Tell us about your role in the Southern California chapter of Women in Bio.

Strause: I was an original steering committee member for this chapter. The chapter has only been around for a little over two years, so it is definitely one of the newer chapters. It comprises an area of CA that includes Los Angeles and areas to the south. The chapter has grown quickly and I believe we now have a very diverse and committed group of women on the steering committee. Currently I am on the program committee and my role is determining program content and executing on it. In that regard I try to focus on timely issues that are of interest to science, such as the recent panel discussion on Rare Diseases.    

I certainly enjoy the networking and meeting people who are excited about bringing new ideas to the table. I find the women in this group enjoy educating others and having the opportunity to give back to the community. So many of them seem to have a passion for teaching and passing along the knowledge they have gained to others, and that is something that I think makes this group strong and valuable to its members.