Talking with Patients about Phase I Trials – ACE Lecture Series

MD Anderson Cancer Center
May 6, 2014

Dr. Baile: So welcome to the ACE Lecture Achieving Communication Excellence. My name is Walter Baile and I'm Director of the MD Anderson program on Interpersonal Communication Skills, and so welcome. And for our guest lecturer today, I'm pleased to present Dr. Wendy Harpham. Dr. Harpham is a board certified internist trained in medicine at the University Of Rochester and then UT Health Science Center.

Dr. Harpham is also a lymphoma cancer survivor who was given--which has given her a unique experience dealing with serious illness. We might say from both sides of the stethoscope and although she no longer practices medicine, her experiences have led her on a career of author , patient advocate, and advisor to group such as the American Cancer Society, ASCO, and the National Cancer Institute. She's the author of nine books on survivorship related topics and many articles and webcasts. Her work has received national recognition including the Tree of Life award from the Leukemia and Lymphoma Society, to Natalie Spingarn Writer's Award from the National Coalition for Cancer Survivorship, and a 2000 Texas Governor’s Award for health. Wendy, thank you so much for coming down and giving a talk on--talking with patients about Phase I Trials.

Dr. Harpham: Good afternoon. I want to start by thanking Dr. Baile and MD Anderson Cancer Center for the honor of participating in this I*CARE ACE Lecture Series. Dr. Baile asked me to discuss the challenges of talking with patients about Phase I trials, partly because of my experience as a subject in early phase trials. But mostly because since retiring from clinical medicines 21 years ago, I've been focusing all my attention on the glue of clinical medicine. Searching for words that help patients make wise decisions, especially regarding their treatment. The conversation about early phase trials is challenging, tapping into dilemmas and all spheres of medicine from molecular biology, to ethics, to healthcare economics, beating at the heart of clinical trials are the competing demands of research and patient care.

First let's look at research. Trials are the modern tool for determining which intervention is work in humans and which don't as well as for assessing how well they work. The faster trials come to completion, the faster researchers can develop more effective, less toxic treatments. A huge obstacle to progress in America is represented by two numbers. Only three percent of adult patients received treatment in trials and only 60 percent of FDA approved trials include the minimum numbers of patients needed to proceed. While I have known these statistics for a long time and have appreciated the differences between trials in pediatrics and in adult populations, these known numbers still astound me every time I see them. If we hope to push progress in improving enrollment, we need to address how clinicians are talking with patients about Phase I trials.

Now, let's look at patient care. Since antiquity decisions have been committed to putting their patients welfare above all else. Newly minted physicians take the Oath of Hippocrates whose words are still inspiring clinicians to cure sometimes, relieve as often as possible, and comfort always. Let me be clear. More than I care about increasing enrollment, I care that each patient making a decision about a Phase I trial makes a decision that is truly informed and in keeping with that patient's values. How clinicians talk to patients about Phase I trials plays a vital role in whether those two criteria are met. So it is that conversation between clinicians and patients that I'm here to address. A medical discussion fraught with emotional, psychological, ethical, and logistical complexity and challenges. For starters, brief end of visit R&R, review and recommend, are thing of the past, replaced by today's lengthy conversations that reflect the increase time needed to discuss the escalating number of tests and the increasingly complex treatment options with a new breed of patient that's coming to the table with preconceptions and expectations about survivorship shaped by a patient empowerment movement and the democratization of medical information. Answering patient's questions takes time and care because patients considering Phase I trials are in some degree of emotional distress having just learned that their cancer has progressed. And if this latest diagnosis with the first time their oncologist couldn't offer the hope of standard treatments, this crisis unlike past episodes of new and progressive disease frightens even tough and veteran survivors in a whole new way.

To complicate matters, many patients are referred for a Phase I trial after standard therapies have been exhausted, and when no Phase II or Phase III trials are available for them. If any of those patients perceive the referral for a Phase I as a routine next step in their care, like past referrals to a surgeon or radiation oncologist with expectation of improvement and not as what it is, namely one of two choices, the other being hospice. Researchers find themselves shouldering the responsibility of introducing the option of stopping cancer treatment, a topic that is delicate and time consuming at best and potentially relationship ending especially at a first meeting. In this setting, making an informed decision depends on patients knowing that hospice focuses on hopeful living and not on dying. But how often do clinicians present stopping treatment as a hopeful choice when talking about Phase I trials? For that matter, how often is hospice not even part of the conversation?

Other conversations are not happening too. Some oncologists never mention Phase I trials to their patients. Not even if standard therapies offer only marginal benefits, not even after standard therapies have been exhausted. They justify the omission saying, "They don't want to stir false hope." Meanwhile, at survivorship events, many patients profess there is no such thing as false hope; that physicians have an obligation to never take away hope. My push for oncologists to talk about Phase I trials to all potentially eligible patients is not motivated by a desire to preserve patient's hope, but by a belief that patients have a right to choose.

Starting with the original cancer diagnosis, patients have treatment choices at every juncture. Science and statistics help clinicians determine which of these choices deserve serious consideration for a particular clinical situation. Clinicians then present the reasonable options to patients, clarifying the risks and benefits, the pros and the cons of each option so then patient can weigh their options and choose. Clinicians who don't mention Phase I trials to eligible patients unwittingly deny those patients a choice, an empowering choice, whatever the patients decide about the trial, whatever the medical outcome. You see, patients who decline trials to enroll in hospice, may avoid despair because they feel more in control of their lives and less abandoned by a medical world than had they been told "I'm sorry, I have nothing to offer you to try to treat your cancer.”

Talking about Phase I trials is not only challenging, it's controversial. Some clinicians argue that since these investigational therapies have no track record in humans, they really shouldn't be even called treatment. A philosophical question reflecting the heightened uncertainty associated with Phase I therapies compared to the uncertainty associated with standard therapies, a factor that adds yet another layer of complexity to the conversation and another layer of stress for patients who are trying to make informed decisions. Some clinicians ask: Is it even possible for patients with terminal disease to make an informed decision about the Phase I trials?” I'm going to have to leave these satellite issues orbiting so we can tend to our task at hand, discussing how to achieve communication excellence in the conversations taking place right now in oncology offices across America.

Today, I'd like to offer a practical approach to decision-making that I call the BEST MED approach. In the context that talking about Phase I trials, the BEST MED approach is one that can help clinicians meet the increasing demands of science and technology and meet the increased needs of modern patients. It's an approach that can help clinicians inform patients about Phase I trials without extinguishing hope and without fostering false hope. But first, the back story.

In 1993, I’d just been diagnosed with my second recurrence of indolent lymphoma, 24 months after completing Promace-MOPP for my original diagnosis, only 9 months after completing mini mantle for my first recurrence, and was still receiving interferon. At that juncture, all standard therapies offered little hope of a durable remission and no hope of a cure. Bone marrow transplant was recommended because of its high remission rates. But in 1993, transplant was associated with significant morbidity and mortality and was too new to know the durability of any of those remissions.

After telephone consultations with lymphoma specialists and tear-filled talks with my husband, I met with my long-term oncologist and then made my decision, to enroll as the 15th and last person in a Phase I trial at Stanford for the first monoclonal antibody therapy to be tested in humans. Now, current health staff talked about that drug, now called Rituximab, the same way they talk about penicillin. But 20 years ago, in a hospital room at Stanford, pouring those chimeric monoclonal antibodies into my vein, recalled the drama of Neil Armstrong's first steps: Researchers were doing something we hoped would represent one giant leap toward curing this so-called incurable cancer, but feared, it would turn out to be ineffective or lethal.

21 years and 6 courses of cancer treatment later, 3 in early phase trials, here I stand, subject number 15 of that Phase I trial, now in my longest remission. It's no wonder some people call me the poster child of Phase I trials. Rest assured, I am fully and constantly aware that most subjects in Phase I trials do not live happily ever after. My personal good fortune and boundless gratitude have not blinded me to the fact that my story is an anecdote, an “n” of one. I hung up my white coat, not my discipline as a physician.

Since 1990, I have been exploring clinician-patient communication not as an academic, not as a researcher, but as a writer. Stripped of my prescription pads since retiring, I have devoted most of my attention and limited energy on the glue of clinical medicine - as I said in my opening - Searching for words that help patients make wise decisions, especially regarding treatment. My understanding of the language that might help patients get good care has been informed by my formal medical education, my work as a primary care physician, and most importantly, by an intense education on survivorship that began the day I was diagnosed with cancer.

For the past 23 years, I've been observing, as a physician, my own thoughts and feelings as a patient. And I've been listening closely to the stories of patients during the hours and hours I’ve spent like an undercover agent participating in support groups, waiting in reception areas of phlebotomy, labs, diagnostic radiology, radiation oncology, hooked up to IVs for chemo - privy to patients' stories that few doctors ever hear. All of these experiences have only strengthened my commitment to advocate for science and to warn patients of the dangers of misinformation and false hope. And that is what led me to my BEST MED approach to decision-making, where B, “Best” is the centerpiece of a verbalized mission namely striving to make the best decision. E, “Empower”, empower patients to assume an active role. S, “Support” patients’ efforts to obtain and process medical information. T, “Tool” for decision-making. And M, “Manage” uncertainty. Now, T and M are really subsets of S, Support, but I've awarded them their own letters because they often get neglected and because for some patients, one or both maybe essential, given how different patients have different needs for information, different decision-making abilities and different reactions to uncertainty. E, “Encourage” patients to do what they need to do. D, “Decide”, the end toward which all BEST MED efforts are aimed. The acronym BEST MED reflects my belief that a shared mission to determine the best treatment path for each patient is the best medicine, not only for patients, but also for clinicians and researchers for progress in cancer care and for the future of medicine. With that overview, let's look at how the BEST MED approach to decision-making addresses many of the dilemmas of modern medicine and modern patient care in ways that meet the twin goals of pushing cancer progress and insuring that each patient's decision to enroll in a Phase I trial is indeed, fully informed and in keeping with that patient's values.

The BEST MED approach begins with verbalizing the mission. BEST, before even mentioning the Phase I trial. My number one goal is helping you determine the best treatment path for you. Clinicians are pressed by over busy schedules. Yet those who profess commitment are not wasting time. In seconds, this declaration may calm patient's fear of being sweet-talked into a trial that needs enrollees, an anxiety that may persist even among patients who are familiar with the increasingly stringent oversight regulations that protect subjects. Clinicians who voice commitment to patient's welfare also address the patient's fear of being treated like so-called guinea pigs, a term still bandied about on social media, if not by skeptical friends and family - people who are not part of the clinician-patient conversation, yet may be key players in patient's ultimate treatment decision. Putting a face behind the legalistic regulations may calm patients' fears and let us help them get in a frame of mind where they can hear and process the medical information. It makes perfect sense. The patients harbor fear of medical care that does not have their welfare in mind. Given one inescapable fact, trials are designed to answer scientific questions, making trial subjects, primarily a means to an end that benefits future patients and not them. Yes, the equation changed with the advent of biologics, while I've had trouble finding consistent figures on this, everyone seems to agree that more patients today are benefiting from Phase I trials and it's a reality responsible for researchers now capturing and analyzing tumor response in Phase I trials. But still, that doesn't change the fact that trials are designed to answer scientific questions about promising treatments that may prove to be ineffective and/or harmful. A legitimate concern of patient is, "Can researchers really want what's best for me?” Yes. I experienced as a trial subject how clinician's commitment to advancing the science can coexist with commitment to patient's welfare, simply by shifting their priorities throughout the day. When doing their research, designing and executing trials, doing statistical analyses, the science is paramount. But whenever clinicians are caring for patients, talking with patients, evaluating patients’ conditions, making treatment decisions, attending to therapies, clinicians take off the researcher's hat and abide by the professional oath as physicians to act in their patient--with their patient's welfare as their top priority. Patients can relate to those everyday active shifting priorities. Clarifying for patients that their welfare is always the top priority may give patients the confidence they need to let go of some of those worries. What about the question of efficacy of investigational therapy given in Phase I trials? Some patients, like me, do indeed benefit. But most patients do not.

The professional obligation to communicate that fact hinges on a distinction between the uncertainty associated with standard therapies that offer marginal benefits and the uncertainty associated with investigational therapies in a Phase I trial. When discussing standard therapies, clinicians strive to inform patients of the known risks without scaring them away from interventions that improve the patient's chance of recovery, an expectation based on statistics for that treatment that justify encouraging patients to focus on the potential benefit, even if it's only a small chance of improvement. In contrast, when discussing investigational therapy being administered in a Phase I trial, that same focus on potential benefit is not justified, because without a track record of efficacy, the chance of recovery cannot be presented as better with treatment than without. People committed to progress in cancer care may worry that if clinicians highlight the limited bank claims of Phase I trials already inadequate enrollment will plummet and hamper progress. I'm not worried because if the truth is framed in the context of striving to determine the best decision for each patient, paradoxically the candor and clarity may encourage patients to enroll. How? By nurturing patients trust. A force that's strengthens the clinician-patient bond. Who would you trust more, shopping for a new computer, the salesperson who steers you to one model, lists all the upsides and concludes this is your best choice? Or the salesperson, who asks you about your computer needs and your budget, directs you to one computer, highlights the upsides and the downsides and then asks, what can I do now to help you make the best choice for you? Whatever you're buying into, trust matters. Clinicians who present all the facts, the truth, foster trust, a force that calms fears that otherwise can be obstacles to informed decision-making. Fears, fears of death, the pain, of abandonment, and so on, aren't the only obstacles to informed decision-making.

Let me tell you. Being a practicing physician did not immunize me to any of the thoughts and feelings or external factors beyond the science and statistics that can be problematic for patients. A list that along with fears includes other emotions such as a wide variety of hopes and desires, such as patient's perception of risks and benefits that can be impacted, skewed by pain, fatigue, past experiences with treatment or patients' orientation toward luck. That includes beliefs, spiritual beliefs, and beliefs about conventional medicine. Social pressures can be problematic too. Let's consider patients whose language of survivorship equates stopping treatment with giving up. If all standard therapies are exhausted, those patients may see accepting hospice as losing their battle - an option that is totally unacceptable, motivating them to enroll in any trial that will accept them. And sometimes it's not the patient per se, but the family who's unwilling to let go and is putting pressure on the patient to enroll, putting pressure to keep fighting. The BEST MED approach heads off this common issue by defining “best” for patients, in essence, defining success in achieving the mission of making the best decision, making an informed decision in keeping with your personal values. For some patients in some settings, clinicians can suggest that the battle imagery that served them well before, may no longer be healing. Whatever patients’ language of survivorship, a near universal threat to sound decision-making is the accompanying stress, compounded by patient's sense of urgency to treat the cancer. Emotions that can make it very difficult for patients to hear and process the medical information. One affirmation that I have found most useful in getting patients to slow down and to mobilize their strengths is more than you want to get going with the plan of action, more than you want to put the stress of decision-making behind you. You want to do whatever you have to do now, to make the best decision about treatment. These few words may help engage patients in a collaborative effort toward best. The medical evaluation is a fundamental step in this collaborative process toward best. Now, patients down play, pain, weakness, or problems with treatment, depression, you know, because they want to qualify for the trial. They jeopardize clinicians’ assessment of risks and benefits. To enhance communication, clinicians can preface the usual history taking with a few words that stress the patient's vital role in the process and this empowers the patient. “Your accurate reporting enables me to make an accurate assessment of what you can expect, so then you can compare your choices and make the best decision.”

Here's the thing, while expectations enable patients to compare their options, it is patients’ hopes that drive their ultimate decision and not their expectations. Be it their hope for recovery, for comfort or for any other hopes that takes center stage at that decision-making juncture. Consequently, framing the evaluation in the context of empowering patients to know what they can hope for may enhance communication throughout any evaluation. Hope between office visits, where patients spend most of their survivorship, hope powers the volleys of information and advice aimed at them by family, friends, and even strangers who somehow heard about their cancer journey. One of the surprises of my survivorship was the volume of unsolicited information and advice about alternative cancer cures. All of which are rejected while undergoing my first two courses of treatment. But with my second recurrence, my standard options dwindled. None offered hope of long-term survival. And that's when I first felt the lure of alternative cancer cures. They offered me a sense of empowerment that I had not experienced when tethered to a radiation table, or hooked up to an IV. Packaged pills and testimonials tagged at my hope, stoking my desire to control the disease that threatened me. My message here is not that my consideration of alternative cancer cures came late in my survivorship journey, or that it was short-lived, but that I considered them at all. That I, the person who spent 10 years actively debunking alternative cancer cures, actively teaching patients, preaching really the difference between knowledge obtained from an anecdote and that obtained through sound science. The message is that I still felt the pull of false hope. Patients get tripped up on this issue of false hope because false hope is a real feeling when experientially similar to the uplifting and energizing feeling of realistic hope. Hope based on sound information. Patients considering Phase I trials are looking for hope. We know that most, if not all of these vulnerable patients are hearing about alternative cancer cures. Thus, clinicians have an obligation to steer patients away from quackery to remove it from the patient's calculus. But how? Just mentioning this charged topic, risks alienating some patients and compromising their trust. So even if clinicians have the time, which they don't, I suggest that clinicians can best fulfill their obligation to steer patients away from quackery by talking about the power of science based realistic hope in determining the best path. This message can then enriched by media materials and to a trained staff who teach patients the warning signs of quackery, clarify the differences between unproven science-based therapies and unproven therapies advertised online or in unregulated clinics. Videos can teach patients what false hope is, how to recognize it. The dangers of false hope such as how it can bring comfort even joy while blinding them to the opportunities for real improvement, while driving them to decisions that go against their values. How false hope always disappoints in the end. Hope an essential element of any conversation that leads to informed decision-making.

Well, what if patients only other options when considering a Phase I trial is hospice? How can clinicians steer patients toward realistic hope? I suggest clinicians specify the one hope that must be abandoned if patients decline the Phase I trial and enroll in hospice. Now, most people assume that this--the hope at stake here is hope of recovery. It's not hope of recovery. It's hope that treatment can help. Hope that treatment can help. Patients in hospice can hold on to hope for recovery for every type of cancer. History documents cases where terminally ill patients stopped all cancer treatment and then unexpectedly and inexplicably recovered at least for a while. Maybe their cancer disappeared because of a delayed response to prior treatments or because of some rare idiosyncrasy of their tumors or immune system that future researchers will ultimately identify making similar recoveries predictable . Or patients can hope not for a recovery but for their disease to progress slowly enough to benefit from a more appealing trial that subsequently opens. Or even better, to benefit from new FDA approved treatments that subsequently become available. Likely? No. Possible? Yes. My last six courses of cancer treatment were not options when I was first diagnosed. Whenever the outcome is at all uncertain, hope for recovery is not false hope. Realistic hope, healing hope, is not about what is likely. it's about what is possible, however, unlikely. While cracking open the door of hope for recovery for patients with a poor prognosis, clinicians can share some insights about hope. Patient's expectation of the likely outcome can coexist with hope for the best possible outcome.

In 1993, I accepted the statistics. I expected to die before my oldest graduated elementary school. I even took some concrete steps to prepare my husband and my children for that possibility. At the same time I accepted the likely outcome. I nourished genuine hope of my being the exceptional long term survivor. Patients can expect one thing and at the same time hope for another. Patient's hope doesn't have to be strong to be healing. When I entered that trial, I did not have a lot of hope of long term survival but the little hope I had helped me live. And each patient has to find a unique balance of hope and acceptance that helps that patient. Now, whether the patients hope is healthy or maladaptive hinges not on the amount of hope but on whether that hope helps or hinders the patient's ability to get good care. A feverish patient with no white blood cells may hope that the fever turns out to be nothing. This is a healing hope. If it keeps the patient calm while being driven to the emergency room; this same hope is maladaptive if it prompts that patient to crawl into bed and not tell anyone about the fever. Day and night, patients are bombarded with messages of hope. Clinicians help patients by guiding them to realistic hopes and then by supporting patients’ efforts to find a balance of hope and acceptance that helps them get good care, whatever levels of hope and acceptance that might be.

The Ancient Roman Philosopher Cicero teaches us while there is life, there is hope. I agree and I'd like to add where there is hope, there is life. That said, letting go of hope that treatment can help can be a struggle because it's an intoxicating hope empowered by the ingrained link between treatment and hope of survival. I mean, think about it. Your patients bald, weak, miserably sick from treatment, keep returning to the clinic for more. Propelled by hope, these toxic treatments can help. For patients to keep the hope of treatment in proper perspective when choosing between Phase I and hospice, they need to appreciate the costs of holding on to that hope. You know patients wonder, what pain and loss will accompany choosing the Phase I trial? What opportunities will I miss by doing the Phase I trial? It brings to mind Robert Frost's famous decision dilemma when "Two roads diverged and sorry I could not travel both and be one traveler.” I can't know what it's like--I can't know what it feels like to let go of that hope of treatment because throughout my survivorship, I have always had options. That doesn't change the fact that when I was considering the Phase I trial, I still needed to understand the costs of enrolling in that trial. Make no bones about it. Subjects are subject to a lot. I had to commute to California which was a great hardship for my husband and his parents who moved into help us. It was a great hardship for my children who never understood why mom kept leaving. I had to comply with repeated follow-up visits, blood tests, CT scans, post treatment biopsy under general anesthesia, none of which I would have needed had I not been in the study. Entering the trial also meant keeping cancer front and center in my life. How could it not be? Which brings me to the great opportunity cost of entering a trial for patients who are choosing between a Phase I trial and stopping treatment.

Choosing to be a trial subject means sacrificing the chance to let cancer drift into the background as much as possible for as long as possible. It means sacrificing the benefits of hospice, letting go of the chance to maximize comfort off cancer treatments, enjoy relationships and the pleasures of life that are still possible as much as possible, all invaluable gifts especially at the end of life. It's not oncologists’ place to be counseling about hospice, rather, what clinicians can do is reiterate their commitment to fostering realistic hopes and simply state that both the trial and hospice offer realistic hopes and then trained staff, can assume the education piece about the specific hopes of hospice, sending patients home with media materials to help patients reflect on their own hopes in the current circumstances. Then completing the healing circle as a support staff to reinforce the message that the patients’ physicians want them to focus on realistic hopes so they can make the best decision for them. If indeed, hopes not expectations drive patients’ treatment decisions, then to make an informed decision, patients need to know the chance of certain hopes being realized. Now, assuming that patients enroll in trials with the hope of recovery, and patients enroll in hospice with the primary hope of maximizing their time, patients' primary hope is very likely to be realized in hospice and not very likely to be realized in a trial. Clinicians who make this clear help patients make decisions in keeping with their values.

And again, I'm not worried about this transparency hurting enrollment. Patients will--I'm sorry--I'm from my New York and I talk with my hands. But patients will continue to enroll in trials. And the reason is that that hope of recovery for the Phase I trial is fueled by powerful survival instincts. An instinct that's hard to repress. And because the hope of recovery is not one hope, but all the hopes of life, my hope for surviving was really the sum of my hopes to rear my children, my hope to keep my husband from losing me, my hope to continue caring for patients in some form or fashion, the top three of an endless list of hopes that included playing my violin, being with friends and family and, seriously, smelling the roses. All of the things that made my life worth fighting for, worth taking great risks for. I also believe enrollment will not suffer because of the great opportunity cost of enrolling in hospice: the real chance that the investigational therapy could have, indeed, succeeded where all standard therapies failed. The real chance of being that pioneering patient, one of the first to benefit from what would subsequently become standard of care. Here is yet another reason to believe that transparency about the efficacy will not hurt enrollments. Those assumptions about patients primary hopes don't apply to all patients.

Some patients, when faced with a poor prognosis, nurture a primary hope that is not hope of recovery and not hope of comfort, but hope of creating meaning out of their tragedy by contributing to progress that benefits future patients. My decision to enter the trial was purely selfish. I entered for only one reason, to help me. Still, my hope that researchers could learn something, that something possibly being to abandon monoclonals and to search elsewhere for better treatments, gave a profound meaning to a terrifying time of loss, and that sense of meaning brought me a tremendous sense of peace. What has meaning is different for different people. Some patients find meaning volunteering for a Phase I trial, others find meaning accepting their fate with equanimity, embracing the opportunity to teach children a valuable life lesson about dying with the guidance and support of hospice to use waning energies to create a legacy of intimate moments that will live on after they die. As for altruism, there's nothing wrong with it playing of role in patient's decision. Look, all around us, healthy people voluntarily accept risk to help others, firefighters, policemen, soldiers, doctors treating HIV patients. For some patients, using their illness to help others is the best path. Meaning, matters. All that said, if patients bring up their desire to contribute to progress, my thoughts are for clinicians to acknowledge the altruistic bent and then draw boundaries regarding any talk of altruism to minimize the risk of unintended coercion to enroll. Many patients find participating in trials meaningful. Meaning, matters especially now, but as your physician, I can't know what source of meaning is best for you. I encourage you to pursue these vital discussions of meaning with people who are not responsible for your medical care, such as counselors, clergy, family, friends. Meaning, matters.

To give meaning to the risks and statistics at play in the treatment decision, I talked to Dr. Baile because I can imagine a short video with actors portraying the thoughts and feelings of four different patients who are dying. One patient regrets having been a trial subject saying she was pushed by her family to keep fighting and she talks about wishing she had used her remaining time traveling, visiting with friends. A second patient has no regrets about being in the trial. She feels at peace, confident she lived the way she wanted to, leaving no stone unturned, having done everything possible. A third patient regrets declining the trial, explaining that she'd mistakenly believed the patients in Phase I trials are denied pain medicines. She bemoans not finding out all the facts about the trials before deciding. And a fourth patient has no regrets about declining the trial, explaining tearfully because dying is sad, how at peace she feels, grateful to have taken control of her life by enrolling in hospice early, living her life to the fullest to the end. Side-by-side stories may help patients project how they feel if treatment does not help, an exercise that may help them prioritize their hopes and accept the uncertainty. Along with AV materials, I see an essential element of support being opportunities for patients to talk with nurses and other non-MD professionals in the absence of physicians. Here, patients can ask questions and share the information that they may have kept secret from their physicians out of embarrassment, wanting to appear strong, or fear of the answer, and thus, in this setting, providing information and insights that may shape physician's assessment or recommendations. Those conversations without doctors present may open opportunities to provide patients additional information, additional insights that prove vital to wise decision-making.

Another element of BEST MED is the next letter, T, a decision-making tool. Again, I say essential because for some patients, using one of the many decision tools available may be key to their making an informed decision. When I was considering that first clinical trial, I was physically sick from the interferon, I was emotionally distressed and I tried instinctively to a decision tool I designed in my practice. It's a set of boxes that put all the critical information on one page, such as, what we knew about remission rates and duration of remissions and response rate among the risks, what are the treatment options we're taking off the table, the impact of treatment on my life, the cost of treatment. I'm going to share my filled in decision tool from 1993 for two reasons. First, to illustrate that the tool facilitates communication by providing an efficient way; one, for clinicians to gauge patients understanding of the facts; and two, for patients to communicate their values. Using this tool, I realized and shared with my doctors that I was unwilling to risk dying from a transplant for the hope of a cure. I valued buying some time using less toxic therapies. The second reason I'm sharing it is to illustrate how trials, Phase I trials, necessarily generate a lot of question marks, which are evidence of the heightened uncertainty associated with undergoing investigational therapies. Well, obviously for me, the heightened uncertainty was not a deal breaker but it was a factor that needed to be addressed, which is why the BEST MED approach to decision-making helps patients manage uncertainty by providing information and insights.

For example, the notion of investigational therapy causing unexpected problems can stir a patient's imagination, complete with horror movie images. Patients can easily reign in that imagination if they're taught that the body has only a limited number of ways to respond to insult, that unexpected problems are usually familiar problems such as unexpected rashes or unexpected blood pressure issues. Patients can be reminded that cancer doesn't make life uncertain, cancer only makes life feel more uncertain by exposing the uncertainty of life. In preparation for concluding the conversation and leaving patients to make their treatment decision, the second E in the BEST MED approach brings attention to the value of taking just a few seconds to offer words of encouragement. I can still remember times that my physicians off-the-cuff comment reverberated in my head for days and helped me through very tough times. And they helped me in ways nobody else's words could. Clinicians can encourage patients by stating how they believe the patient now has all of the information and tools they need to make a wise decision, how they have confidence in the patient's ability to make a wise decision, how they will support whatever the patient decides.

At last, the big D, the final step, decide. Now, by definition, clinicians are not part of the autonomous decision. But with communication excellence preceding the final step, clinicians’ insights and information and encouragement may continue to guide and support the patient through their solo effort. So, there you have it. The BEST MED approach to decision-making, an approach that can foster communication excellence by building trust and by engaging patients to learn and talk about their choices every step of the way by choosing words that encourage and empower patients. The BEST MED approach fosters a collaborative relationship with patients having as active a role as they're able and desire with medical issues addressed in the context of patients’ values and with the goal always front and center, enabling patients to make an autonomous, informed decision in keeping with their values. I'll close with an anecdote. My approach to achieving communication excellence hinges on the idea articulated in Talmudic teachings, that if you save one life, you save the world. You've seen my medical history. What you didn't see was my world.

This photograph was taken just a few months before I was staring at the fork in my road. Where long I stood, looking at my treatment options including the Phase I trial, thinking about what lay ahead from me, ahead of my husband, ahead of 8-year-old Rebecca, 6-year-old Jessica, 4-year-old William. I took the road of the Phase I trial. That unproven treatment changed my world keeping me in the picture and that has made all the difference. This photograph of me and Jessica catches the essence of the hope of clinical trials. It was taken in a National Cancer Survivors Day celebration on the day before I left for Stanford to enter the first Phase I trial. As a scientist, I knew that trial would likely mark the beginning of a downward spiral to the end. But my hope, a realistic hope, in a science-based if unproven therapy, calmed my fear of tomorrow.

I did not have a lot of hope that day, but the little hope I had helped me embrace my life under the circumstances. The hope that the novel treatment might work gave me a moment of happiness that made life worth living, whatever happened with the trial.

Phase I trials are designed to answer scientific questions with data. But those dispassionate dots on the far right side of survival curves are in fact people, each of whom represents a whole world, with no meaningful utility value, a price tag on all the ripples in the universe made by anyone patient's life. Let's continue the conversation about how to talk to patients about Phase I trials. With respect and with hope, I wish each of you the best in your efforts to achieve communication excellence that helps patients obtain good care and live as fully as possible today, tomorrow, and every day. Thank you.

[ Applause ]

[ Inaudible Remarks ]

Dr. Harpham: So, we have a time for a question or two. Anyone? So--Did you? Yes.

Speaker: You talk about [inaudible] making a decision consistent with values. I would like you to clarify more about what you mean by values, what exactly could be--

Dr. Harpham: Well, like for example I said that I--I was in a support group where there are number of us young parents, young kids at home, with lymphoma, trying to make a - recurrent lymphoma - trying to make a treatment decision. And most of the other parents chose to go with bone marrow transplant which in 1993 was very exciting because the remission rates were wonderful. And there was this culture the sense of the bigger the guns the better. And they looked at their young kids and they said, "I need to go for the cure.” But when I was looking at my choices, and looking at my young children, my youngest of whom still would not have known me--from me, he would have only known from pictures had I died at that time. I cared more about living long enough that my son would one day say, "Oh, mom do you remember when we did this?” I wanted to be in their lives now. So, I valued buying time and not trying to go for the cure. Buying time, my primary hope being my kids would know me. But my secondary hopes being if I bought time then more trials, better trials would open. If I bought time, new treatments would come on the way. Again, I looked at what it meant to have that transplant. And again back then, it meant a long hospitalization, significant morbidity, mortality. And as a doctor, I knew that my life, my body would be forever--after changed in terms of future risks and quality of life. I valued buying time with less toxic therapies.

Is that helpful?

Speaker: Yes.

Dr. Harpham: Did you have a question? No. OK. So, anyone else?

Speaker: So, what do you--what would you suggest because a situation I think that folks may run into a lot, when, you know, the patient really values quality of life and is intimidated by the toxicity of a Phase I trial but is getting pushed by the family.

Dr. Harpham: Right.

Speaker: You know, I don't think it's an uncommon dilemma that your families are handling a different kind of set of psychological pressures.

Dr. Harpham: Right. I think there are two issues,

Speaker: OK.

Dr. Harpham: One is concern about toxicity needs to be addressed. And just as I mentioned that unexpected medical problems are usually familiar problems that are treatable. I think it's really important to emphasize that choosing the trial does not obviate full attention to patient comfort. Palliative care should be involved and I believe it is involved here, throughout. And patients need to be reassured that in the trial everything will be done to pay attention to, and address physical, emotional, spiritual comfort. So, that's not going to be thrown out if they choose the trial. The other big issue is a communication, ethical issue and that is, it's the patient's life. It's the patients decision and families need to be supported in understanding that sometimes the best way to show love is to respect the patients values, needs, decisions when it's in conflict with what you want for the patient, let alone what you want for yourself. That's where I think the BEST MED approach has its strength because it serves to ensure the patients are truly informed in a transparent comprehensive way about the expectations and the hopes of the trial and the expectations and the hopes of hospice or a Phase 2 or off label standard whatever option they're looking at, so that then they can interpret what is known in the context of patients values.

Dr. Baile: OK. Well, thank you very much Wendy and we really appreciate you coming and giving us--

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