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00:01:29: Welcome to another episode of The Effective Statistician Today.

00:01:33: I'm super happy Very nice and experienced.

00:01:38: And awesome to work with a colleague here, Julia!

00:01:42: How are you doing?

00:01:44: I'm good thank-you.

00:01:44: how're you doing?

00:01:46: very Good and excited to talk about the topic that is very close my heart.

00:01:52: patient reported outcomes.

00:01:54: It's really important because i think all we do in The end Is for the patients if it can't help.

00:02:02: so patience.

00:02:03: well What do we do?

00:02:05: Exactly.

00:02:07: All the endpoints about patient-reported outcomes are one way to put patients back into the center of clinical research, but before we dive into this topic maybe you can introduce yourself and how have got interested in patient reported outcomes.

00:02:26: Sure, sure.

00:02:28: My name is Julia Poritz.

00:02:29: I'm a senior research consultant at Cytel on the evidence value and access team with Alexander And how i got interested in patient-reported outcomes probably started back in graduate school...I don't know that we called them PROs but of course we were very interested in the patient voice both in clinical setting And so we need a way to measure the patient voice.

00:02:57: We use measures completed by patients themselves, which of course now we call Patient Reported Outcome Measures and much of the research I did during graduate school then in my postdoc fellowship focused on various PRO measures.

00:03:13: So if i look back at it now probably all began even when using that term PROs.

00:03:21: What has been your experience in terms of working with PROs, researching PROs during your professional career?

00:03:30: Yeah.

00:03:30: I would say most of my experiences have either developed measures for a special population or validating an existing measure Prior to joining Cytol, that would have been in various health-related populations like spinal cord injury or traumatic brain injury.

00:03:50: And of course now at CytOL we work with a broad array of indications although I'd say it's primarily oncology and rare diseases.

00:04:00: Yeah i think so.

00:04:00: the topic said rare disease especially where you very often need to develop something new because there is nothing established for specific needs at population.

00:04:12: So, if we want to think about developing new piroes.

00:04:17: We need some framework.

00:04:19: so could you walk us through how different aspects like actually the disease symptoms functioning piro and ultimately also quality of life which I think very often is considered a Piero they all relate each other?

00:04:37: Yeah, you're right.

00:04:38: We definitely need some sort of framework or model to be able to consider all of these concepts together and one of the most widely used frameworks is The Wilson & Cleary Model.

00:04:49: this Is a model of health related quality-of life And it considers All those aspects that You just mentioned and lays out A framework for how they are Related To each other.

00:05:00: we know That somebody's disease Or the treatment They receive For It ultimately has an impact on their overall quality of life.

00:05:09: But it's probably not a straight line, right?

00:05:12: There are all those other factors you mentioned in between.

00:05:15: So the great thing about this Wilson and Cleary model is.

00:05:18: it shows how something like your disease or your treatment has an impact on symptoms that you experience, the symptoms might then have an impact upon your functioning which affects your overall perceptions of your health and well-being and that ultimately hasn't impacted on your overall quality of life.

00:05:38: so having a framework to think not just to conceptualize the relationship between all these different factors, but also to start coming up with a plan for how you can practically use PROs or PRO measures.

00:05:56: So let's go for an example yeah?

00:05:58: Let say we have oncology indication.

00:06:02: head and neck answer is the tumor.

00:06:05: that obviously at area And now the therapy can shrinks the tumor in size.

00:06:12: Now, that is really on the lowest level directly to the disease levels.

00:06:18: But what are then following these symptoms functioning?

00:06:21: How does it build for example this indication?

00:06:25: Exactly, and that's a great example.

00:06:27: So like you said if there is a treatment that causes reduction of the tumor then will have an impact on the person's symptoms And so for example There might be some localized pain That has been caused.

00:06:42: as the tumor reduction occurs The pain can reduce.

00:06:47: Then think about how it would affect their physical functioning.

00:06:51: Once they're physically functioning improves.

00:06:54: that then has an effect on their perceptions of their health.

00:06:58: Oh, my pain is reduced I'm functioning better on a daily basis i'm starting to feel more optimistic about my overall health and well-being.

00:07:08: And so then that leads into this broader concept of overall quality of life.

00:07:13: So you could theoretically take any health condition and treatment and walk through in that sense the impact starting with disease and treatment all the way through symptoms, functioning health perceptions.

00:07:26: And then ending up with the overall impact on quality of

00:07:29: life.".

00:07:30: So if we think about that reduces a pain... ...and so maybe it could have an impact or stability to swallow which has an ability to eat which increases the quality-of-life?

00:07:45: Yes, exactly.

00:07:47: And the model also includes other things like individual characteristics environmental characteristics so that we keep in mind That this doesn't all occur within a vacuum.

00:07:57: there are other things going on in patient's lives But will have an impact on their quality of life as well.

00:08:03: What could be?

00:08:04: these other factors said haven't had an impact?

00:08:07: Yeah, that's a great question.

00:08:09: So in terms individual characteristics, if somebody maybe has a pre-existing condition prior to this head and neck cancer.

00:08:16: That's something to keep in mind is that conditions still ongoing?

00:08:20: or maybe it's resolved but there's some anxiety about recurrence while they're dealing with the head and net cancer...that's an individual characteristic that understandably will probably have an impact on their overall quality of life!

00:08:33: And then if you think about Are they living in a situation that's stressful?

00:08:40: Maybe if you've lost their job or there having some sort of financial stress, so that could be an environmental factor.

00:08:47: That also has an impact on their quality-of life.

00:08:50: Yeah very good!

00:08:52: So one topic I found really interesting about is when you create the development plan... You need to have something called patient reported outcome strategy.

00:09:05: Why do we need a strategy and what is that actually about?

00:09:09: Yeah, it's a great question.

00:09:11: I think the strategy could be defined in different ways but an easy way to think of it.

00:09:18: as an umbrella term four of the buckets that I often think about are identifying your PRO measures, implementing your measures, analyzing the data and then reporting their results.

00:09:35: So those four categories could fit under.

00:09:38: There'll be different things that fall into each of those buckets as you progress through your strategy.

00:09:47: But it's important to have a plan, because you want to make sure from the outset that you're selecting appropriate measures and then you need also planned to implement them an analyze data And of course, you need to plan at the end how you're going to communicate and disseminate the results.

00:10:04: So from start to finish there are all these aspects that require advanced planning and preparation to ensure that you have a cohesive PRO strategy.

00:10:16: so when I think about the first step in selecting superheroes what would be factors that drive my selection?

00:10:24: So given that there are actually Pierrot's in this area.

00:10:29: Yes, you're right first You need the measures to exist.

00:10:31: yes and thankfully There Are a lot of measures out there.

00:10:35: so you're wondering what factors into The decision-making process about selecting these measures?

00:10:41: It is a multi faceted process.

00:10:44: Ultimately, it does go back to the patient voice and the patient experience like you mentioned earlier.

00:10:50: So You need to examine The qualitative research that is available in your specific indication To get an understanding of what the patient Experience Is?

00:11:00: In that indication What really matters to patients because he want to make sure you're measuring what really matters them.

00:11:08: so you have to take into consideration the patient Voice.

00:11:13: You also probably need to take into consideration any precedent.

00:11:17: Are there studies that have already finished or in progress?

00:11:21: What measures are being used in those studies, if you're planning to compare results later on... You need to have some sort of alignment between the past studies and your study.

00:11:33: so that's something you have to keep in mind.

00:11:36: And then another thing to think about is how the treatment will have its impact.

00:11:44: So like you mentioned earlier with the tumor reduction, you need to make sure that what your measuring is not just important to the patients in that indication but it's also relevant.

00:12:03: starting early on, you can come up with a plan to make sure your selecting the best possible measures.

00:12:10: It definitely should pick-up treatment effect otherwise it's pointless.

00:12:18: of course this also needs to be in line with what regulators demand from such patient reported outcome and who has payers will demand

00:12:32: Exactly.

00:12:33: You need to make sure you're using validated measures because if you are using something that's not validated, your going to encounter issues.

00:12:39: so thats also a really important piece.

00:12:43: So we talked about the implementation analysis and then publication reporting factor in these three areas.

00:12:53: is there anythings that would like tell listeners?

00:12:57: it was very important for them where things go wrong.

00:13:01: Oh, well I guess it all goes back to planning having a plan in place and that could look different for each of these areas.

00:13:09: For implementation some things we think about are when the measures will be collected?

00:13:16: In what order they'll be administered the potential burden to the patient if there are too many measures or they're too lengthy.

00:13:26: So in terms of implementation, that's when it gets very logistical and nature trying to figure out best way implement these measures you've selected because at this point we have the best possible measure for our purposes.

00:13:40: so then make sure your actually implementing them pretty logistical in nature.

00:13:47: In terms of the analyses, it goes back to like you said that treatment effect and being able to demonstrate with your analysis that there is an effective treatment on your PRO endpoints.

00:14:01: And then in terms of reporting we may not often see this but ideally if can see the PRO results the efficacy analysis, that's an ideal situation.

00:14:17: And there are all sorts of different reporting guidelines that can be used to ensure that results is reported in appropriate way.

00:14:27: and so thats really important as well too.

00:14:29: make sure we're using best standards possible

00:14:38: for clinical trials, strobe and Prisma.

00:14:42: And many other statements that help you on set.

00:14:47: I think i talked about this in an earlier episode so probably need to just search for it in my archives but this is a really important part.

00:14:57: one of the parts that was struggling with when working at German affiliate or big company was unique translations.

00:15:07: Yeah.

00:15:08: So just having the English version is not sufficient, probably Not even if you run your study Just in the US.

00:15:18: That's correct.

00:15:19: And so Having something that is understandable to Your local patients Is really important.

00:15:25: and then there are ways How we can have a validated translation and things like this.

00:15:30: But make sure You Have enough time planned for doing these Things.

00:15:35: Yes exactly it's very lengthy process that it involves translation and backtranslation, and validation.

00:15:43: And there are some concepts that work really well in one language that don't work so well in another language.

00:15:50: for example we might have a measure in English And in some places there's.

00:15:56: no, that just doesn't work out right?

00:15:59: You can't say I'm feeling blue.

00:16:02: So when you translate a measure and validate it another language It could end up being pretty complicated process.

00:16:09: Yeah In German i am feeling blue means i'm drunk

00:16:15: so That would not work for the measure.

00:16:18: yeah When we think about such strategy what will be good point to start with it, overall clinical development plan.

00:16:28: Do you need to do this already before phase one or what's the timeline?

00:16:32: Let's say that earlier they're better but there is not necessarily a bad time to get started so doesn't have to be early than Phase One and Phase Two are probably fine starting points for implementing measures.

00:16:48: So I don't necessarily think there's a bad time.

00:16:51: You can, given that the PRO strategy can encompass a variety of different activities even if somebody comes to us at the very end just needing guidance or assistance with dissemination we can always support with that.

00:17:05: so there is no bad time.

00:17:06: thinking about your PRO Strategy but in an ideal world probably earlier on would be better.

00:17:13: Yeah early one At least said you have some already in phase two So that you have data for your phase three study.

00:17:22: Yes,

00:17:23: and I also really want to emphasize again the comparability with other drugs.

00:17:30: so once worked in an area where The company i worked was wanted to do things better And choose yeah a better patient reported outcome That it was different to all the others.

00:17:46: So any comparisons, network meta-analysis.

00:17:49: All these didn't work or at least it worked as good as they should and that created all different problems.

00:17:58: so I think there's sometimes there is a balance you need to meet in terms of what do when doing this kind of things.

00:18:08: Exactly yeah!

00:18:09: There are many measures we consider legacy measures which have been used extensively but maybe weren't developed with the most sophisticated methods.

00:18:21: And so now we have newer measures that are much more robust, But like you said if your planning for an indirect treatment comparison You're going to run into a roadblock where you won't be able To compare your new more sophisticated measure With the older legacy measure.

00:18:37: So it's definitely something to keep in mind.

00:18:41: Once We did a specific study But it was actually not even a clinical trial where we had sent both girls included.

00:18:50: so that is, that we can easily match one on the other.

00:18:55: And that helped a lot with translating them

00:19:00: to

00:19:00: different effects.

00:19:01: That must have been really interesting.

00:19:03: Yes!

00:19:03: That was fun.

00:19:05: Thanks very much Julia.

00:19:07: Of course It's awesome to have you.

00:19:09: Is there any final thing?

00:19:12: tells the listener about Piero's strategy, Keith take a very point.

00:19:17: Yeah I would say it all goes back to what you mentioned at the beginning that ultimately what we're doing is for patients and so their voice in their experience needs to be incorporated.

00:19:29: We are not just checking a box to say oh we included Piero or we reported on Piero.

00:19:34: It's So much more than that!

00:19:39: And to that end, if anybody wants to learn more about PyroStrategy there's a great free resource.

00:19:46: That was put together by the National Cancer Institute in Isoqual.

00:19:50: they created A Free Webinar and it is available on The National Cancer institute YouTube page.

00:19:58: So for anyone listening who would like More information About Pyro Stratagy thats Available

00:20:09: on the blog of this episode.

00:20:11: Thanks so much, Julia!

00:20:13: Thank you for having me

00:20:15: and I'm really looking forward to continue working with you.

00:20:18: Likewise thank you Alexander.

00:20:25: This show was created in association with PSI.

00:20:29: Thanks to Rain and her team at VVS who helped with the show-in-the background and thank you for listening.

00:20:35: Reach your potential, lead great science and serve patients.

00:20:39: just be an effective statistician.