March 8, 2013
NIH Podcast Episode #0185
Balintfy: Welcome to episode 185 of the new NIH Research Radio. The new NIH Research Radio is your source for weekly news and information about the ongoing medical research at the National Institutes of Health – NIH . . . Turning Discovery Into Health®. I'm your host Joe Balintfy, and coming up in this episode our news summary at the end of the program includes items on genes related to age-related macular degeneration and how environmental conditions influence influenza.
But first, our feature story...
Patient reported outcomes in cancer
Balintfy: The scientific community, including governmental agencies like the NIH and FDA, plus numerous professional organizations and other national groups in recent years have been coming together to better understand the effects of new drugs and therapies on patients. The idea is to not only know how those drugs and treatments work, and what changes may be happening to an underlying disease, like cancer for example, but also to know that during the treatment process, patients aren’t being made worse with adverse effects, like nausea, hair loss or pain. Researchers and clinicians – the medical staff treating patients – are using patient reported outcomes to help. Patient reported outcomes are basically surveys or questionnaires; we’ll get more details on that later.
I’m talking today with Dr. Sandra Mitchell; she’s a research scientist in the Outcomes Research Branch at the NIH’s National Cancer Institute. Dr. Mitchell, when cancer fighting drugs or treatments are being tested in clinical trials, how do researchers measure whether or not the benefits outweigh any adverse effects.
Mitchell: So that’s a great question and we evaluate the benefits of a treatment or what we might call therapeutic response. We typically evaluate those benefits through diagnostic studies that confirm either that there’s less tumor burden or that the intended target for our therapy has been successfully modified in some way so that we are really having an effect on the underlying disease.
We’re also interested in evaluating the benefits of treatment using patient reported outcomes and using performance based assessments essentially evaluating how people feel and function. Because not only is it important to try to stabilize or shrink ideally the tumor or hit whatever molecular target we’re attempting to hit, but we also want to be sure at the same time that there may be important improvements in how people feel and function as a result of bringing their tumor under better control. We call of that therapeutic response.
As you mentioned, we’re also interested though in adverse effects because those do have to be weighed and balanced.
For adverse effects in cancer, we have two main systems for evaluating those. We have the Common Terminology Criteria for Adverse Events or CTCAE, which is what clinicians have classically used to evaluate the adverse effects of treatment.
We are also developing a companion system to that that allows patients to directly self report adverse effects that they’re experiencing and this the patient reported outcomes version of the CTCAE really focuses on adverse effects that are best evaluated by the patient and those are predominantly symptoms.
So we’re interested in the patients evaluating adverse effects such as itching or nausea or headache and these may emerge as a result of treatment. Clinicians can evaluate them but as clinicians we’re probably not in the best position to evaluate those. We really ideally like to get those reports directly from the patient and that’s what we mean by a patient reported outcome.
Patient reported outcome is any measure of health status, symptoms, functioning, anything that comes directly from the patient as far as a report and that’s why we call it patient reported outcomes.
Balintfy: How are patient reported outcomes measured?
Mitchell: We predominantly measure them using surveys or questionnaires and those questionnaires are typically structured to ask about the concern using plain language. So for example if I’m interested in finding out about the patient reported outcome of fatigue then I will say ‘what was the severity of your fatigue’ and then I will ask you to tell me about that severity using a standardized response scale. It might have five points, it may have ten points, there’s variation in that but typically it would be on a five-point scale where when I ask you about the severity of your fatigue, you would rate it all the way from none or zero all the way up to four or five, which would be most sever fatigue imaginable. Patient reported outcome measures are these survey questions. There’s variation around how those are actually phrased and designed but predominantly they follow that kind of a model.
Balintfy: Are there challenges associated with patient reported outcomes? I guess it’s pretty easy to measure a tumor to see if it’s growing or not but are there variations or challenges with patient reported outcomes?
Mitchell: Well I would actually say that sometimes measuring particularly in today’s age of molecularly targeted agents where we sometimes have the goal of stabilizing the tumor but also hitting molecular targets, determining therapeutic response is still a really big challenge using imaging studies and other kinds of things. Similarly, in patient reported outcomes, we do have some challenges although it can be very straightforward to gather a report from someone about how much fatigue they have or how much pain.
The challenges that we encounter in patient reported outcomes can be around things like are you feeling really too sick to kind of complete some questions, might you speak a different language than the language in which our questionnaires are available. We do make our questionnaires available in a wide range of languages but we don’t have every single language. Similarly, it may be that someone speaks the language well but does not read that language and so because patient reported outcomes sometimes require reading, some of the barriers around literacy can pose challenges. We have overcome this in patient reported outcomes and we actually have overcome it with the PRO-CTCAE system by offering to ask these questions via phone to people and we call that interactive voice response. So people that say ‘yes I would prefer rather than looking at the questions on a piece of paper or answering them on a website, I’d like to have them posed to me verbally by phone and I’ll press buttons on my keypad to indicate what my response is.’
So our predominant challenge around collecting patient reported outcomes, we certainly have some logistical hurdles and then we also have interpretative hurdles as well too. Because it can be challenging to understand whether severe fatigue means the exact same thing for each person. Part of that is not only because we’re each individual people and so something that bothers you with severe fatigue may not bother me. Fatigue is probably not the best example of that but for example skin itching might be something or someone who says I’m concerned about appearance changes you know, I might say that I’m very concerned about appearance changes and somebody else might say you know what, ‘I really don’t care. If this treatment is effectively treating my tumor, I really don’t care what kind of appearance change I might have to endure because of this.’ So we’re all individuals and that can make the interpretation of patient reported outcomes a little bit challenging.
Similarly, a lot of our patient reported outcomes the degree to which you’re bothered by something also is influenced by what you have to do in your daily life. So people at middle age and young people who have very high demands between school and work and family may be very bothered by things like fatigue. Someone else may say, ‘you know, I have a little more time to myself and I can pace myself during the day and so yes I have fatigue but it really doesn’t interfere or bother me.’
Interpreting a patient reported outcome is not quite as easy as it might sort of look on paper but we are definitely, we have a number of very robust and well-studied methods for disentangling some of these issues that I’ve touched on. We also technologically have a wide variety of ways of gathering the patient reported outcomes either by the web, paper and pencil, through interview, or through regular telephones and through handheld computing devices or smart phones.
So we also just like therapeutic response where new technologies are coming down to evaluate the effectiveness of cancer treatment, we are similarly developing technological ways to collect these outcomes efficiently and routinely.
Balintfy: I’m not sure that my next question sort of flow into that but I’m curious why it is important, why do you think it’s important to include patient reported outcomes, this kind of research in clinical trials?
Mitchell: That’s a terrific question and I think that it’s a question that I would say scientific community has already begun to respond to. The US Food and Drug Administration has a new initiative that they are calling patient centered drug development. As well numerous professional organizations as well as a number of governmental agencies and other national groups have over the last several years been really coming together to say that if we’re really to understand the effects of new therapies on patients, we not only need to know that it works, that it changes the underlying disease entity that we’re seeking to change and improve but we also have to know that in the process we don’t make people worse. And we also really need to know even if we change the underlying disease how do people feel and function while they’re receiving this therapy, what are the challenges that they encounter. Because if we know more about those difficulties and challenges and side effects that people might be experiencing, we can actually implement supportive care to make therapies more tolerable and contribute to sustaining people’s quality of life while they’re on in this case cancer directed therapy. But this could apply to a variety of chronic diseases.
So it’s really important in the development of new therapies for us to know that this works on the tumor and the treatment target. It’s important to know what are the adverse effects and then it’s very important to know what are the effects on the individual person of this whole treatment experience. Patient reported outcomes are the ideal way to gather that third aspect of the understanding that we really need.
Balintfy: How do you see this being integrated? How will differences in what patients and physicians report in clinical trials be combined?
Mitchell: So that’s a great question and it’s one of the remaining key questions that we have in the development of this patient reported outcomes version of the CTCAE. Because the Common Terminology Criteria for Adverse Events or CTCAE has classically been a clinician reported system where the clinician evaluates the severity of the adverse event and records that in the research chart, as we start to see how do we bring in the patient perspective, we are really challenged to try to understand how do we balance clinician perception with patient perception.
Indeed, we believe that likely the way this will get integrated is that clinicians evaluate symptomatic treatment, toxicity by talking to patients. They don’t make up the toxicity. They don’t just decide, take a good look at the person from across the room and say your fatigue is a grade 4. They talk to the person, interview them, ask a series of questions where we try to understand the severity of something and how much interference it’s causing and then we use the grading system to assign that a grade.
With PRO-CTCAE, we’re trying to streamline and create a more direct way for clinicians to gather the patient experience and to integrate that into the grading. So this not only more direct but it also ensures that from clinician to clinician, we’re evaluating this in a consistent manner and that we are gathering these reports in a consistent manner directly from the patient as well too. So it’s consistent scoring of it and consistent gathering of the information.
Balintfy: That wrapped up the questions I had but I thought maybe one last question to kind of bring this maybe to a person, how would I experience this? So would I only find out about the PRO-CTCAE if I were volunteering in a clinical trial or if you were a patient and how would I know that I’m interacting with that?
Mitchell: So that’s a great question. Right now, we are still in the phase of developing the patient reported outcomes version of the CTCAE. So we are testing it in several cooperative group cancer clinical trials and patients who are participating in those trials are invited to also complete the PRO-CTCAE measures weekly during their participation in the trial. We actually find that patients welcome the opportunity not just in our trials but this is a well-known and well-established component, the patients welcome an opportunity to contribute their perspective. In fact, many times patients are really aching to communicate what their experience is.
So people that are participating in PRO-CTCAE are assigned a log-in. They are given a choice if you’d like to complete questions by web, by phone, or on paper. If you would choose to compete by web or by phone, you would log into the system using either one of those preferred devices and then you would have a series of questions posed to you about how you’re feeling. Generally, we would ask about things like fatigue and hair loss, itching, pain, nausea; but we also ask about a number of other symptoms that clinicians may less commonly bring up. For example, we ask about urinary difficulties. We may ask about bowel function. We may even ask about whether anyone is experiencing sexual side effects such as loss of libido or problems with erectile dysfunction. So that’s another advantage of this system is that actually we can gather information about some side effects that maybe unaddressed in a clinical interview.
But people will have then an opportunity to respond to those questions using the web or the phone and as they participate each week, they can look at the trend and their responses over time. When they complete the survey, those results are actually sent directly to their treating clinician so the next time their clinician sees them that clinician would have a printout of those results that they can use to guide their interview of the patient. Also if the patient wishes, they can also print out a copy of their results, their responses to take with them to the clinic.
We really envision that for many patients as this system is integrated into routine practice of cancer clinical trials that many patients will find that that’s a really helpful tool for communication with their clinician, maybe also a helpful tool for understanding your own progress over time. You may be able to say ‘wow well I’m still fatigued but actually over time my fatigue is actually getting a little bit better so here’s what I’ve been doing to do that, let me do more of that. Here’s what I haven’t been doing, you know, let me step it up and do the things that my clinicians told me I need to do to treat my fatigue.’ So we ultimately hope it will strengthen communication between patients and clinicians as well as strengthen patient’s abilities to manage to the best of their ability their own symptoms and to follow the recommendations and guidance they’ve been given by the team.
Balintfy: This maybe and oversimplification but it sounds like it’s a way to get the patient more intimately involved with the study.
Mitchell: Absolutely and I think that’s not an oversimplification at all. It really is a tool for greater patient engagement.
Balintfy: I think that wrapped up the questions I had. Is there something maybe I missed or something that you would want to reemphasize?
Mitchell: I think it is really important and patients are aching to be much more involved in their own therapies and we critically as clinicians and researchers need to understand the effects of treatment on the individual patient in how they feel and function daily. Patient reported outcomes are an ideally suited method to gather that information. We have good tools and a wide variety of tools at hand and the challenge that we face now and that we’re attempting to surmount with systems like PRO-CTCAE and also like other systems like the Patient Reported Outcomes Measurement Information System or PROMIS. What we’re attempting to do with all of these systems that are complimentary to each other is to efficiently integrate this into the clinical trials enterprise. Make it easy for people to provide us with this information in their busy lives and really leverage some of these exciting new technologies that we have with worldwide web but increasingly with mobile computing devices.
Balintfy: Thanks to Dr. Sandra Mitchell in the Outcomes Research Branch at the NIH’s National Cancer Institute. For more on patient reported outcomes and the PRO-CTCAE, visit the website: http://outcomes.cancer.gov/. Also, be sure to tune in next month – you can hear about that PROMIS system that Dr. Mitchell mentioned. For now, those news stories on the genetics of age-related macular degeneration and how environmental conditions influence influenza, that’s next here on NIH Research Radio.
(BREAK FOR PUBLIC SERVICE ANNOUNCEMENT)
Balintfy: Now for some recent news headlines from NIH, here’s Craig Fritz.
Fritz: An international group of researchers supported by NIH has discovered 7 new regions of the human genome that are associated with increased risk of age-related macular degeneration, or AMD, a leading cause of blindness. The consortium’s work adds to 12 previously identified regions of the genome that are known to influence the disease. AMD affects the region of the retina responsible for central vision, and is what humans rely on for tasks that require sharp vision, such as reading, driving, and recognizing faces. As AMD progresses, such tasks become more difficult and eventually impossible. Some kinds of AMD are treatable if detected early, but no cure exists. An estimated 2 million Americans have the disease.
A study by NIH researchers has shed some light on role of climate in the transmission of influenza. Two types of environmental conditions—known as cold-dry and humid-rainy—are associated with seasonal influenza epidemics. The study provides a model that maps influenza activity globally and accounts for the diverse range of seasonal patterns observed across temperate, subtropical and tropical regions. The findings could be used to improve existing influenza transmission models, and could help target surveillance efforts and optimize the timing of seasonal vaccine delivery.
For this NIH news update, I’m Craig Fritz.
Balintfy: You can get more information on these news items at www.nih.gov/news. Also, you can get monthly health information from the NIH News in Health newsletter. The march issue has features on keeping your kidneys healthy, soothing a sore throat, and more. Find that at http://newsinhealth.nih.gov.
And that’s it for this episode of the new NIH Research Radio. Please join us again next Friday, March 15 when our next edition will be available. Coming up in that episode, a diabetes study and improving A1C measures…
More people are meeting the goals in these three key markers of diabetes control. It went from 2% in 1988 and is 19% now in 2010. That’s the good news. The bad news is that 19% of people are meeting all three goals, which means there’s still plenty of room for improvement.
Balintfy: If you have any questions or comments about this program, or have a story suggestion for a future episode, please let me know. Send an email to NIHRadio@mail.nih.gov. Also, please consider following NIH Radio via Twitter @NIHRadio, or on Facebook. Until next week, I'm your host, Joe Balintfy. Thanks for listening.
Announcer: NIH Research Radio is a presentation of the NIH Radio News Service, part of the News Media Branch, Office of Communications and Public Liaison in the Office of the Director at the National Institutes of Health in Bethesda, Maryland, an agency of the US Department of Health and Human Services.
About This Podcast
Spokesperson: Dr. Sandra Mitchell
Topic:cancer, cancer research, cancer treatment, cancer drug, drug, treatment, patient, patient reported outcome, PRO, PRO-CTCAE, PROMIS, survey, questionnaire, clinical trial, clinician