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103 Issue 3 Interview Transcript

Kristine Crane: Welcome to the JNCI podcast. I'm Kristine Crane. In the past two decades quality of life measures have been increasingly included as endpoints in clinical trials. For breast cancer in particular the large number of trials has made it possible for researchers to examine not just whether a treatment is working but how it makes a woman feel. I talked with Dr. Patricia Ganz of the Jonsson Comprehensive Cancer Center at UCLA. Dr. Ganz wrote a commentary about a review of quality of life measures in breast cancer clinical trials. So, welcome Dr. Ganz.

Dr. Patricia Ganz: Hello.

Kristine Crane: Why don't you tell me a little bit about the study that you wrote about?

Dr. Patricia Ganz: Okay, well Dr. Lemieux [ph?] and colleagues went ahead and looked at the literature on breast cancer clinical trials between 2000 and 2009 to examine studies that had included quality of life outcomes as part of the investigations of the clinical trials as another endpoint either as the primary endpoint or more often as a secondary endpoint in the clinical trial. And this was a follow up to a study that had been done earlier by Dr. Goodwin and myself. Dr. Goodwin is actually an author on this paper as well. And the idea was to see if over time there had been both methodological improvements in the way in which quality of life endpoints were measured and incorporated into breast cancer clinical trials and where they may make a difference in terms of the interpretation of those trials.

Kristine Crane: And what did the study find?

Dr. Patricia Ganz: Well they found that a large number of new trials had actually been added to what we had found earlier. Initially I believe we found some 66 articles originally that we reported on and in their update they found 190 new additional articles of this follow up nine years so it really shows an expansion of the number of clinical trials that are including quality of life in them. And they also were able to examine, because there were larger numbers in each of the categories whether the quality of life outcomes added value at various kinds of trials, so surgical and radiation trials for local treatment versus adjuvant chemotherapy trials versus trials for metastatic disease or trials that were psychosocial or behavioral interventions. So they had many more numbers of studies within each of those categories.

Kristine Crane: And where did they find that there was most value where quality of life measures were being used in the clinic?

Dr. Patricia Ganz: Yes. So I think the real issue is, you know, it would be great if it didn't cost much time and money to include quality of life in every clinical trial because obviously describing the patient's experience adds some benefit. But there are many situations in which you're comparing two treatments that are so similar that the sensitivity and precision of the quality of life questionnaire is not sufficient to detect differences. So examples of where this may make a difference is if you're comparing an endocrine adjuvant therapy to a chemotherapy adjuvant therapy, the quality of life reporting seems to be quite good in terms of picking up differences that would be important to patients. But if you're comparing adjuvant chemotherapy A to adjuvant chemotherapy B where you're just varying one or two drugs in the treatment regimen most of those patients recover in terms of their overall quality of life and you can't detect a difference that's meaningful.

Kristine Crane: Okay. What about in the metastatic setting, I mean I know that a lot of advanced cancer therapies can be quite toxic and people already have a sort of diminished quality of life.

Dr. Patricia Ganz: I think the important message from this review in terms of looking at clinical decision making differences based on the quality of life endpoint is if you have a therapy that's a real winner, let's take the drug Herceptin which really transformed the treatment of patients with metastatic breast cancer who had very aggressive tumors, that treatment made such a difference in terms of impact on survival that even if the quality of life were poorer in those patients and I believe the studies were done did not show that but let's just say for argument most patients in the metastatic disease setting would take that very effective therapy. And so there there's not a lot of added value to doing the quality of life but when two treatments are very close in what we think the outcome is going to be then knowing if one adds more burden to the patient and the toxicity may be more severe would be very important. So it's very hard for trial designers to know up front what the outcomes are going to be so one has to be cautious in terms of burdening patients with advanced disease with collecting quality of life data unless you think there are unique toxicities that may make one drug regimen more preferable to the other.

Kristine Crane: There has been quite a jump in terms of the number of studies that are actually looking at quality of life measures. Is part of that, is that a sort of ongoing trend, is part of it due to advocacy work perhaps to encourage patient voices?

Dr. Patricia Ganz: I think there are two things. Number one, there are lots of breast cancer clinical trials so it's a patient population that's studied a lot with new treatments and so there's a lot of research going on just in terms of management and drug development and so forth. The second thing is that, patient advocacy is very important, people certainly do want to know if certain treatments make a difference and they can certainly inform how we manage treatments but we also have a lot of questionnaires that are very well worked out. I happen to work with one of the cooperative trials groups and we basically wherever there is a meaningful question in terms of a comparison of treatments they've been very willing to add these kinds of questionnaires into the trials. Just an example a very large central node biopsy trial that was done, women having their lymph nodes removed versus not could have a big impact on arm function, swelling, mobility as well as quality of life and in this particular trial we were able to look at multiple aspects of the impact. So sometimes you have this kind of once in a lifetime opportunity to really look at comparison of different treatment toxicities from a very comprehensive way and I think that's where quality of life really adds value.

Kristine Crane: Now do you think that breast cancer is sort of leading the way for other cancers?

Dr. Patricia Ganz: Well, I think it has been in many, many ways because we do have multidisciplinary teams, surgeons, radiotherapists, medical oncologists, pathologists are really working together, people who are interested in the psychosocial aspects are often integrated into both the clinical management and multidisciplinary care but also into the research teams. And that is becoming obviously more of the norm with other kinds of cancers, but I think breast cancer's been quite a bit ahead and has made it a good demonstration area for these kinds of studies and pursuit of this kind of research.

Kristine Crane: Okay. And so how do you think that this present study or these measures could be improved if we were to see a part three, since this is part two?

Dr. Patricia Ganz: Yeah. Well I think reviewers basically looked at the quality of the designs and the way the studies were reported and there were some things that were found lacking. Many of the studies didn’t have good statistical analysis plans. In the previous review some of the quality of life questionnaires that were used were not quite up to par, the quality of them was now better, there's more coalescence around several common instruments that are being used. So the quality of the tools to measure quality of life has improved. But as with any kind of research methodology until the trial designers and the journals that are publishing these articles raise the standard so that the designs are done well, the research is conducted in an appropriate way we will not see perfect studies. And it takes often 20, 30 years for this kind of methodology to get embedded within standards of research methods. But as I commented in my editorial, many of the studies that were published between 2000 and 2009 were actually designed probably in the mid 1990s and so they were reflecting the methodologies at that time whereas studies we would design today in 2010 are going to be much better in terms of the statistical designs, looking for ways to prevent missing data in terms of the longitudinal data collection as well as the general acceptance by the physicians, nurses and patients that this is important data to capture. So all of those things will make the next review whi

Kristine Crane: Just to sort of sum up then, why do you think that we're seeing more quality of life measures?

Dr. Patricia Ganz: Well I think patient centered care and patient reported outcomes are where things have moved. And looking at efficacy in terms of whether a treatment is-- one treatment is better than the other is very, very important. And again as the review actually points out, at least in breast cancer, patients are looking for the edge in terms of treatment and if the treatment is better they will in fact want to take that better treatment because they want to have a long term survival and they'll put up with a lot of toxicity for a small benefit. That's not true for other diseases, but that's the case in breast cancer very often. But if the treatments are equivalent, let's take the example of losing your breast with a mastectomy or having a lumpectomy and radiation and preserving the breast, there's absolutely no difference in survival for those treatments, they're absolutely equivalent. But wouldn't it be important for the patient to know what her life is going to be like if she has mastectomy versus if she has a lumpectomy and radiation? And so those are kinds of things that only quality of life data can give you in terms of knowing what the patient experienced. There's no difference in survival but the experience for the patient in terms of physical, psychosocial, emotional, body image, sexuality, all those things may be very important and may weigh on whether she would want to choose one treatment or another.

Kristine Crane: Thanks again.

Dr. Patricia Ganz: Okay. All right. Well thanks a lot.

Kristine Crane: That was Dr. Patricia Ganz of UCLA. For more information on this podcast or for a transcript of it or to listen to more JNCI podcasts, please visit our website at www.jnci.org. You can also follow us on Twitter at jnci_now. I'm Kristine Crane. Thank you for listening.

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