Ethical Issues

Guest Expert Christine Grady, PhD, RN, FAAN: Phase 1 Trials – How do you balance hope with reality?

Last Updated: Aug 30, 2012

I am pleased to welcome Dr. Christine Grady as our AccrualNet Guest Expert.Dr. Grady is the Chief of the Department of Bioethics at the Warren G. Magnuson Clinical Center, National Institutes of Health and head of the department's section on human subjects research.  She is the author of over 40 published papers in bioethics, HIV disease, and nursing that have appeared in books and scholarly journals, including the New England Journal of Medicine, JAMA, Journal of Medicine and Philosophy, Nursing Research. Dr. Grady is a Senior Research Fellow at the Kennedy Institute of Ethics, a fellow of the American Academy of Nursing, and a fellow of the Hastings Center.

Dr. Grady's current research interests include research subject recruitment, incentives, vulnerability, and international research ethics. In her post below, she discusses findings related to phase 1 trial participation, some of which I found surprising and all of which I found interesting. What are your thoughts? Join the conversation by posting a comment or responding to the questions below.  

Dr. Grady's Post:

Phase 1 studies are an essential step in the quest to find safer and more effective cancer treatments. Yet, people sometimes worry about the ethics of recruiting individuals for these studies. One concern is that those eligible for participation in phase 1 studies are ‘vulnerable’ because they are usually individuals with advanced cancer who have exhausted standard treatment options, are still seeking alternatives for attacking their cancer, and may not appreciate the purpose and potential outcomes of participation. Some worry that the oncology clinical setting and the often hazy line between what is clinical treatment for cancer and what is investigational results in confusion or misunderstanding both on the part of research participants and health care professionals.

The NIH CC Department of Bioethics has conducted several important recent research projects that show that although the picture of phase 1 oncology trials is complex, it is not as bleak as some tend to paint it. In one study, we reviewed response and toxicity data for CTEP sponsored studies conducted between 1991 and 2002. We found that the overall response rate across all types of phase 1 oncology studies is higher than previously reported (10.6% rather than an overall <5% response rate). We also found that only about 20% of the studies and the 10,000 participants were in classic phase 1 dose escalating trials of single agent chemotherapies; in fact, almost half of the phase 1 trials included an already approved drug. Thus, when thinking about potential risks and benefits of phase 1 trial participation, participants, oncologists, caregivers and others should be aware of the variety of phase 1 trials and evaluate potential risks and benefits for each specific trial.

In an evaluation of phase 1 consent forms from US cancer centers, we found that, contrary to fears, most consent forms do not overpromise or overstate the benefits of participation in phase 1 trials and are careful about laying out potential risks, including the possibility of death. Consent forms continue to be too long and complex, however, and indiscriminately use words like therapy and treatment, which could contribute to misunderstanding about the promise of phase 1 trials. We developed a consent template specific to phase 1 oncology trials that builds on the generic consent template developed by the NCI and provides language-in both English and Spanish- specific to phase 1 trials for any group to use or adapt.

We also analyzed data from several studies and found that adult phase 1 participants are primarily white and well-educated, and overall have near normal performance status, some form of health insurance, and received previous cancer treatment. These data challenge assumptions that as a group, phase 1 participants will have a compromised ability to understand information provided to them or to make choices about participation in studies.

In another study of participants at 5 sites, we found that although phase 1 participants usually do hope for anti-cancer benefit, they are usually aware of alternative options such as palliative care and hospice but rarely seriously consider them. Many of these participants are willing to accept a significant chance of harm (including up to a 10% chance of death) for a small chance of benefit. As caregivers and research team members, we should be aware of the power of hope, which can sometimes be positive but also can potentially accompany harmful misunderstanding or misconceptions about research.

The individuals who contribute to progress in finding better cancer interventions through participation in phase 1 studies deserve our respect, our appreciation and our best efforts to protect their rights and welfare in research. What do you do to ensure that potential participants understand the risks and benefits unique to phase 1 studies? How do you present alternatives to participation? How do you balance hope with reality?

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Originally posted by: maryfred on the former AccrualNet site on Apr 27, 2012.

I work as a study coordinator and was new to cancer research when I was diagnosed with AML. I was immediately admitted to the hospital for a bone marrow bx and blood work to see what subtype I had. Before we were hardly settled in the room, and hadn’t really digested the diagnosis yet, I was approached to be in a phase 1 study (they needed to be consented prior to the bx). Having been on both sides I understood why they approached me when they did. The coordinator was very warm and took a great deal of time explaining the study. If the bx came back and the results showed I couldn’t qualify for stem cell transplant I would meet criteria for the study. He explained the risk in great detail, and explained to me that I did not have to participate in the study. They had a medical oncologist explained to me what my path would be if I did not participant in the study with the same bx results. Even though there was a time issue for the coordinator to get my consent, I did not feel pressure of having to make a quick decision. They took the time to talk to my spouse and answer his questions also.

So my key points are:


  • I believe we do an injustice to our patients by not offering them all options of care, research and clinical.
  • I believe we need to allow time to explain the details and risk of the study, understanding that ever person learns differently and taking the time to make sure they have a good understanding of all aspects of the study.
  • I believe it helps to have this conversation with family members is possible. They often will think of questions that the patient can’t at the time.
  • Having the physician explain all of my options for treatment and not making me feel pressure that the study is the best one was important to me.
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Originally posted by: Anonymous on the former AccrualNet site on May 15, 2012.

Maryfred - Thanks for sharing your experience about being on the other side of the informed consent process. You make some great points.
Annette Galassi

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Originally posted by: Anonymous on the former AccrualNet site on May 15, 2012.

Dr. Christine Grady and Dr. Connie Ulrich, two of AccrualNet guest bloggers, delivered last week's NIH Clinical Center Grand Rounds. The title was, Reframing Informed Consent: Understanding How Research Participants Make Decisions. Watch the videocast by cutting and pasting the URL below into your browser. I hope you enjoy the presentations as much as I did.

Annette Galassi

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