Bringing the PRO to fruition

pharmafile | May 14, 2018 | Feature | Business Services, Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing |  PROs, feature, patient reported outcomes, patient-reported outcomes, pharma 

Patient-reported outcomes are becoming increasingly respected and valued by clinical professionals in the pursuit of improving treatment outcomes, but their evolution is not a smooth-sailing affair, as Matt Fellows uncovers.

Trends in healthcare have been shifting towards a patient focus for some time as traditional attitudes have been scrutinised and called into question, leading to the rise in personalised treatment and other methodologies eschewing the notion that patients can be grouped together in one homogenous heap. Along with this has come greater emphasis on the importance of the viewpoint of the patient, which is undoubtedly a good direction for the industry to be moving in.

The use of the patient-reported outcome (PRO) as a measure of success is not new; the tool is still in a slow process of development, but has been growing in prominence and is increasingly finding its way into discussions among industry professionals on how to refine treatment approaches to achieve the best outcomes. 

According to Dr Ameeta Retzer, Research Fellow at the Institute of Applied Health Research, University of Birmingham, an institution at the forefront of research into PROs: “A patient-reported outcome is any report of the status of a patient’s health condition that comes directly from the patient themselves, without interpretation of the patient’s response by clinician or anyone else.”

PROs hinge upon the crucial shift in focus from the clinician’s perspective to the patient’s. This may seem like an insignificant move, but it is a marked progression from more traditional attitudes, as Dr Thomas W LeBlanc, Associate Professor of Medicine, Division of Hematologic Malignancies and Cellular Therapy at Duke University School of Medicine, and Director, Cancer Patient Experience Research Program at Duke Cancer Institute, notes: “Research clearly shows that patients do better than their clinicians when it comes to accurately describing how they feel,” he told Pharmafocus.

“That sounds obvious, but the historical assumption has been that clinicians know what their patients are going through because we all ask how they’re feeling. But it’s clear that by collecting patient experience data via PROs in more structured, systematic ways, we can glean more deep and accurate insights about what our patients are going through. When patients report their experiences via PROs, clinicians thus get a much more meaningful depiction of the patient experience, and can then use that information to enhance the care they provide, perhaps by more actively addressing those symptoms and problems that otherwise might have gone unnoticed.”

However, Dr Retzer is keen to point out that while this shift has occurred and is developing as the prevalence of PRO use increases, the clinician’s perspective is not being eclipsed by the patient’s; she stressed that the two sides of the coin must be taken in tandem in order to be truly effective, particularly when it comes to the design of clinical trials. The increased use of PROs in clinical trials is not intended to be in lieu of other outcomes. In fact, the complementary nature of PRO data when used in addition to other outcomes in trial settings has been demonstrated,” she remarks. “It has been found that patients’ own reports better reflect their daily health status and clinicians’ assessments better predict unfavourable clinical events. When used in combination, both forms of data provide clinically pertinent information that warrants their inclusion in trials.”

Taking centre stage

In the past, PROs have tended to be a secondary consideration, as opposed to the analytical weight they are progressively attributed with today, as Dr LeBlanc explains: “PROs have historically been research tools. They have been used as secondary endpoints in clinical trials, to probe for differences in patients’ experiences of illness when treated with a new therapy, for example. They’ve also been instrumental in helping us to better understand and describe what patients go through when they live with a serious illness like cancer.”

However, despite their obvious potential, PROs have been dogged by a number of obstacles which have prevented that potential from being realised.

“Mostly they haven’t been tools that clinicians use when actually seeing patients,” Dr LeBlanc continues. “There are several reasons for this, one being that until relatively recently, these tools could only be administered on paper, or via very cumbersome standalone systems that don’t readily integrate into clinical workflows. PROs also often require some type of ‘scoring’ method to be applied, which isn’t easily done on paper. Thus amid these barriers, PROs just haven’t been feasible to be integrated into routine care practices in the clinic. Thankfully, technology has evolved tremendously in recent years, and these developments are making it more feasible to electronically assess PROs as part of routine care practices in ways that are less disruptive, or even helpful, in clinical workflows.”

Today, the use of PROs has advanced with the advent of more robust digital systems and other methods which clearly outgun the restrictions of paper-based systems, as Dr LeBlanc notes. As the potential of PROs when married with an effective digital collection system becomes more apparent, not only would this combination be more efficient and practical – it would result in the collection of more valuable data too.

Dr Retzer explains: “With the ongoing use of PROs, the potential of electronic PROs, or e-PROs, has been a subject of interest. Particularly in areas where PROs are routinely used and with the expansion of their use into new therapy areas, streamlining their collection in terms of ease of administration, upholding data capture rates, and managing costs is becoming increasingly pertinent. E-PROs include the use of tablets, websites and apps and would be used instead of paper formats, allowing for their completion to take place in clinical settings and remotely. There has also been mounting evidence that PRO data, when collected electronically, is more likely to be associated with optimal data collection; better participant compliance; higher quality data that is more accurate and complete; improved protocol compliance; and fewer secondary data entry errors.”

However, the same obstacles still remain, principally due to the fact that there has been no real standardisation of the use of PROs as yet, while the effectiveness of e-PROs are neutered if the data they gather never finds its way to a database.

“PROs are being collected in various ways, and there really isn’t a standard yet. Some practices still use paper, though this is problematic regarding clinical workflows, time pressures, and calculation of scores,” Dr LeBlanc remarks. “Others are using standalone apps, however these are problematic if they don’t integrate into the electronic record; clinicians are already pressed for time, and are not excited about having to interact with another system or website, in addition to the already burdensome interactions we all face with electronic records systems.

“Regardless of the collection system used though, it’s most important to collect PROs that are actually actionable. Symptom assessment scales translate readily to action in the clinic; a patient with persistent and refractory nausea requires further attention and prescribing. Overall quality of life scores are of less clear utility. Clinicians don’t know what to do with a quality-of-life score at a single moment in the clinic, though these kinds of metrics are indeed very useful in research, and at the population level and when trackable and trendable over time. The selection of PRO instruments that can actually impact care is particularly important.”

Trial and error

PROs can also be instrumental in the design of clinical trials and in evaluation of their effectiveness, which is why they’ve been increasingly incorporated within them, as Dr Retzer notes:

“In a clinical trial setting, PROs ensure the patient’s experience of a condition and treatment are represented in health measurement and when considering the effectiveness of clinical interventions. From 2007 to 2013, there has been an increase in the number of clinical trials that use a PRO measure – of 97,736 registered trials, 26,337 (27%) were found to use one or more PRO measures. This trend is likely to continue, particularly within the context of a general move towards patient-centred research and care, as well as the development of formal PRO guidance from regulators.”

While the lack of standardisation of approach in the application of PROs is proving problematic in a wider context, there are protocols on their use within clinical trials – namely, Patient Reported Outcome Measures (PROMs). But which to apply is a matter that must be carefully considered, Dr Retzer says.

“PROs are collected using PROMs, which are standardised, validated forms completed by trial participants to measure their perceptions of their own functional status and wellbeing. These might be delivered in a range of formats, including paper or electronically, and could be presented as questionnaires or diaries, for example,” she explains. “PROMs can focus on physical symptoms, treatment toxicities, psychosocial problems or global health-related quality of life (HRQoL) and many other relevant constructs. The matter of choosing a PRO to use is dictated by the research question of interest and what is the phenomenon or endpoint to be measured. Once this is clear, the available PROMs may be reviewed to ensure that they are appropriate to evaluate that endpoint; reliable when used in the population of interest; have content and construct validity; are sensitive to changes in the endpoint; and that they use appropriate recall periods and response scales. In addition to these, one must then consider whether there are scoring guidelines available so that the PRO data may be interpreted.

“PROs should be used when assessing concepts that are best known by the patient or measured best from the patient’s perspective,” she adds. “As such, the means and measures used to record this data must be reliable and considered in the early study design stages of clinical trials. This way, the choice of PROM will be driven by clear research objectives, the rationale for their use will be clear and their implementation strategy can be considered and detailed thoroughly.”         

The big C

Oncology is unsurprisingly the most dynamic and contested therapeutic area in the industry today, so it stands to reason that clinicians would be looking to employ PROs and reap their benefits in the treatment of cancer – given the gravity of the disease, drawing out these benefits is doubly important, as Dr LeBlanc explains:

“PROs are particularly important in cancer care because our patients are facing potentially fatal side-effects and complications, and are facing very life-changing diagnoses and situations. There’s more opportunity to make a difference by attending to patients’ symptoms and experiences. For example, if we can detect problems earlier and more often, we could intervene earlier, and perhaps help patients better tolerate treatments that otherwise will help them achieve their goals, or even help keep patients from having to go to an emergency room, or be admitted to the hospital. While these kinds of issues exist in other fields too, they’re more high-stakes and frequently-occurring in cancer care, particularly in those patients receiving active therapy, and those with more advanced disease.

“Integrating patient-generated health data into cancer care can improve care, and amplify the patient voice. That’s clear,” he adds. “Now we all need to focus on doing the hard work together, of optimising data collection and integration efforts in the context of clinical workflows.”

Clearing the way

While the use of PROs present a clear benefit in the pursuit of better clinical outcomes, their current status as a relatively nascent tool means there are still many challenges to overcome. According to Dr LeBlanc, a major issue is that their burgeoning growth is stifled by the lack of adequate database facilities for them to be entered into – something that would allow for much greater connectivity, providing much wider and deeper analysis into the insights they reveal.

“The biggest problem right now is the failure of most PRO efforts to actually integrate into the electronic record,” he says. “Everyone seems to be building apps for everything, yet most of them don’t actually integrate into the EMR, nor into the clinicians’ workflow. This is ultimately the ‘kiss of death’ for most apps. Integrating patient-facing PRO data collection, via apps or otherwise, into the actual EMR data and the clinical workflow, is really the ‘holy grail’ of work in the PRO space. To date, it hasn’t really been done well.”

Again, the common theme around lack of standardisation or commitment to greater adoption emerges, highlighting that their use is outpacing the existence of infrastructure needed to fully realise their potential. Dr Retzer agrees, but pointed out that some are pushing for progress in this regard:

“The SISAQOL Setting International Standards in Analysing Patient Reported Outcomes and Quality of Life Endpoints Data Consortium is also working towards developing recommendations to standardise the analysis and interpretation of PRO data. Currently, the use of diverse PRO analysis methods makes it difficult to compare PRO findings and undertake meta-analyses. SISAQOL aims to produce guidance to facilitate the generation of more reliable findings that are easier to interpret and can be rapidly disseminated.”

Moving onto challenges within the clinical trial space, Dr Retzer reflected on some of the other issues she feels are holding PROs back: “There are some practical challenges that may be encountered in the administration of PROMs in a clinical trial setting. Due to the subjective nature of PROs, the conditions under which the measures are completed are crucial to upholding the integrity and quality of the data. 

“As such, when these conditions are not pre-specified or conveyed adequately to those implementing the PRO, inconsistencies in PRO delivery may arise that can undermine or bias the data, giving rise to concerns about its quality and utility. This has implications for the potential impact of these data. These inconsistencies may be due to quality of training provision; logistical issues relating to how the questionnaire may be completed or the presence of data monitoring and missing data processes; and managing patients’ and researchers’ burden or distress resulting from PRO completion. These barriers may be overcome through the use of initiatives […] so that clarity and detail relating to PRO rationale, implementation, and collection may be promoted.”

What else needs to be done to shift some of these key obstacles from the path? PROs as a tool are becoming rapidly legitimised as their strengths, and also weaknesses, become more and more apparent, but their growth still seems muted by conditions they exist within. Again, the conversation turns to the need for infrastructure and industry attitudes to rise to meet the requirements that professionals such as Drs Retzer and LeBlanc identify, and cultivate an environment where PROs can be embraced, fine-tuned and brought to fruition.

Stressing that the way forward lies with increasing awareness and literacy with the tool, Dr Retzer gives her thoughts: “Improved visibility and accessibility of PRO-related training, informational resources, and expertise are required so that PROs are successfully adopted and implemented in clinical trials. […] This may take place through their adoption and promotion by stakeholders involved throughout the research process, with corresponding measures to ensure adherence and compliance with best practice. For this to be achieved, stakeholders must be aware that their responsibility to uphold scientific, methodological, and ethical rigour extends also to PROs, but additionally, resources designed to support best practices must be integrated in such a way that their use becomes viable and does not over-burden stakeholders.”

Dr LeBlanc instead brings his scrutiny squarely on the necessity of complementary technologies, without which PROs are considerably weakened, to step up to the plate: “Ultimately, I don’t think we will be able to more meaningfully and consistently integrate PROs into cancer care until electronic medical record (EMR) manufacturers move into the 21^st century with their functionality and user interface designs. One-off, standalone PRO systems are not ideal, and aren’t the long-term answer. As EMRs hopefully become less cumbersome for clinicians, we will have more opportunity to meaningfully integrate patient-generated health data into cancer care, to amplify the patient voice and ensure that patients’ concerns are more at the forefront of each contact they have with the healthcare system.”

The University of Birmingham’s Centre for Patient-Reported Outcomes Research will be holding its annual PROMs Conference on 20^th June this year, bringing together international experts, clinicians, patient partners and early career researchers to engage with the latest advances in the field of PROMs research and implementation.