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Patient reported outcomes: Putting the patient first

Published on 08/05/17 at 11:44am

With clinical practice marching towards a more precision-oriented methodology, assessment of treatment efficacy is undergoing a transformation. Matt Fellows explores the exciting potential of a technique which is helping to maintain the patient as the focus of medical objectives.

The world of treatment is changing. In the past, entire patient groups were stratified as one faceless mass with their individual circumstances homogenised and addressed with simplified, catch-all solutions – but scientific opinion in now shifting. Of course, this approach was perfectly understandable given the relatively more rudimentary state healthcare found itself in decades ago, but popular professional thought now places the patient at the centre of all treatment. Patients today are increasingly recognised for what they are: individual cases with unique needs, and this has driven the rise of precision medicine in the life sciences industry and beyond.

Beyond this, any methods used to assess the effectiveness of treatments would appear inherently flawed were they not to take into account their benefit to the patient at the core of everything they did. After all, what is the purpose of healthcare measures if they do not truly provide value for the patient and improve their quality of life in a way they can tangibly recognise? Yet this is exactly what has been happening in the past, and the limitations caused by this seemingly obviously error were responsible in part for the birth of what we now call patient reported outcomes, or PROs.

In its most basic sense, a PRO is any assessment on the efficacy of a healthcare measure as reported by the patient who received it. Traditionally, the success of an outcome would be determined and reported by the professional who administered the relevant therapy, but this obviously omits the key detail of patient experience. Failing to adequately account for the success of a particular treatment as reported by the patient on the receiving end can lead to methodologies becoming largely ineffectual to significant portions of therapy groups. It is in this way that PROs maintain a focus on the benefits that a specific treatment can provide for its recipient, by consistently cross-checking healthcare data as reported by clinicians against the perceived effects a patient experiences.

PROs can take many forms, from self-administered questionnaires to patient interviews, but a key point is that they differ starkly from their more conventional, professionally-reported counterparts in that they are specifically severed from clinical assessment. In other words, the information generated by the patient is not interpreted on a professional level by the clinician, and is utilised purely on its own analytical merits. This results in the collection of patient-centric data, which can then be archived and assessed in a number of ways, perhaps most interestingly as supporting evidence in the drug application process, backing up assertions of product efficacy made by manufacturers.

The patient-centric nature of the PRO becomes especially significant when put into the context of the WHO’s definition of ‘health’, as determined as far back as 1948: “a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity.” Even this description appears to place the patient’s experience at the heart of any treatment – while the elimination of debilitating ailments is certainly the aim of any therapy, ultimately it is the patient’s experience and quality of life that matters.

Grace Turner, Research Fellow at the University of Birmingham’s Centre for Patient Reported Outcome Research explains: “The term ‘patient reported outcome’ includes measures of both quality of life and symptoms. PRO use has increased exponentially over the past two decades, with a rapid rise in 2009 when the FDA released guidance to industry on the use of PRO instruments to support labelling claims. PROs are self-reported by the patients and their goal is to provide a unique perspective of health and wellbeing from the patients’ perspective.”  

On the rise

PROs are seeing increasing use in the field and are becoming more and more valued by clinicians as an assessment tool – but what impact have they made on modern treatment? Turner asserts that “PROs are extremely valuable to provide patient-centred data for use in both research and routine clinical care. In the context of drug development, patient perspective is critical. PROs can be used to characterise treatment benefit through the measurement of health status; symptoms and side-effects; health-related quality of life; and satisfaction with treatment. The ultimate aim of drug development is to improve patients’ health and quality of life and PROs can capture data on outcomes which are meaningful to the patient. Increasingly, PROs are being used to inform drug licencing, health policy and clinical guidelines.”

Professor Jose Maria Valderas Martinez, Academic General Practitioner and Professor of Health Services and Policy Research at the University of Exeter, agrees on the value of the tool, but argues that it is not without its drawbacks: “The focus on the source of the information – the patient – has indeed been beneficial for the main goal of ensuring that patient perceptions of the impact of their medical conditions and the associated healthcare on their overall health have been taken into account, but this has come at the cost of leaving unaddressed matters and frequently being imprecise about the more substantive issues of what is actually being measured.”

Dr Martinez’s comments warn against an over-reliance on the technique, despite its accepted benefits. As is the case with most precision or patient-centric methods, this is a key concern, and they must be exercised in tandem with other more traditional, tried-and-tested tools in order to be truly effective in improving treatment.

However, Dr Martinez is clear that he does not wish to undersell the impact PROs have had, and will continue to have, particularly in the sphere of drug development: “PROs are now part of the routine repertoire of outcomes in the evaluation of pharmaceutical products and they are here to stay. They are now more valuable than ever, because they embody key aspects of patient-centeredness as applied to perhaps the most important question in healthcare: what are we trying to improve, and who has a say in that decision?”

This utility of the PRO in New Drug Approvals is validated in the report [Assessment of PRO Label Claims Granted by the FDA as Compared to the EMA] by Ari Gnanasakthy [et al], which notes that, over a four-year period, 47% of the 75 approvals by the EMA were supported by at least one PRO-related claim. By comparison, the FDA utilised PROs in 19% of cases. This reliance on the tool has only grown with time. However, Turner was keen to point out that simply because they can be used to reinforce evidence on drug efficacy and safety, does not necessarily mean they are guaranteed to accelerate the approval process. “Although regulatory agencies are increasingly interested in the used of PROs, we are not aware of any evidence that PROs facilitate more expedient drug approvals. PRO data adds to the evidence but may not necessarily facilitate more expedient approvals,” she notes.

Patient-doctor collaboration

As mentioned previously, a key difference that separates PROs from more conventional forms of outcome reporting is that the data they generate are distinct from which would traditionally originate from a clinician or other outside source. But why is this such a significant difference? Turner sheds light on this importance: “It is well known that clinicians and patients view clinical care differently. In addition, evidence suggests clinical indicators, when used alone, can underestimate the impact of a disease for patients and overestimate the effectiveness of healthcare interventions. Therefore, it is important to capture patients’ perspectives, in addition to other clinical outcomes, to provide the full picture of the patients’ treatment experience. PROs provide a unique perspective on the physical, functional and psychological consequences of treatment and the degree and impact of disease symptoms.”

She continues: “From a treatment perspective, PROs can promote patient-centred care and facilitate shared decision-making. PROs have a wide variety of uses, including screening for health problems; monitoring and communicating patients’ health state; supporting clinical decision-making; and evaluating quality of care.”

This idea of ‘shared decision-making’ is key to effectiveness of the PRO. Like many tools in the clinical armoury, its true effectiveness is realised when used in combination with other methods, complementing established processes and ironing out their inefficiencies and shortcomings.

However, while the technique is indeed complementary in part, Dr Martinez asserts that PROs present an entirely new perspective not possible through conventional methods, even in their simplest execution:

“There is good evidence that PROs correlate at best moderately with outcomes as reported by health professionals,” he explains. “Perhaps more importantly, the same is also the case for the correlation between PROs and test-based measures of functional capacity. In morbidity-adjusted models, PROs as simple as a single item question on self-reported health status have demonstrated the ability to independently predict outcomes such as use of health services and mortality. This demonstrates that PROs are not just an alternative approach to measuring health, but rather a unique way of capturing aspects of health that cannot be accounted for by standard clinical measurements of clinician’s perceptions.”

A spur for drug approval?

Since they began to enter the clinical consciousness, PRO use has grown within the industry. Sparked into more popular use since their original applications – which were “largely due to their incorporation in drug labelling”, according to Turner – evidence shows that the use of PROs as an assessment measure during clinical trials has steadily increased since 2007, and current opinion suggests that this growth is not set to slow any time soon. On the contrary, PROs are given the thumbs-up by the medical professionals who see the majority of their working use, and adoption is expected to be continually driven by the industry’s key regulators on both sides of the Atlantic thanks to their utility in the drug approval process.

“The pharmaceutical and drug development industry have indeed seen a rise in the use of PROs, stimulated by the clear endorsement of the regulators,” explains Dr Martinez. “Both the FDA and the EMA have developed guidance on using PROs in the evaluation and approval of pharmaceutical products which has significantly shaped the uptake of PROs by the industry for more expedient drug approval. Whereas previously academia had been one of the main sources of development of PROs, industry has been very quick to play a leading role in this area and this situation is likely to continue in the future.”

This value is of particular note given the current political climate in the US. The Trump administration has so far in its short lifespan made it abundantly clear that it is bent on accelerating the FDA’s drug approval process. Fixated on stripping away unnecessary dead weight to speed the access of patients to life-saving drugs, President Trump’s plan began with his much-maligned ‘one-in, two-out’ regulatory policy, and has culminated with his nomination of Scott Gottlieb as frontrunner for the position of Commissioner of the FDA – another highly divisive move among his critics. With this mission in mind, tools such as PROs which directly address functional issues in the collection of adequate efficacy data, could present a more robust, alternative method in accelerating new drug approvals without the need to gouge out the regulatory heart of institutions such as the FDA. However, taking into account Turner’s earlier comments, this may need to be achieved through a two or three-pronged approach, utilising the strengths of PROs in unison with other tools.

However, despite these benefits, Dr Martinez argues that clinicians have often tended to use PROs in a more myopic manner, whereas perhaps they could be more useful when utilised in a broader context with regards to the generation of patient and treatment data:

“This has also resulted in the development of numerous and mostly very specific PROs which have created a sort of Tower of Babel in PRO measurement,” he explains. “The projection is for PROs to move away from developing bespoke tools, with a narrow focus on specific conditions, in favour of the development of large item banks for a very efficient and reliable outcome measurement, and the selection of those measures that are relevant for the patient population. In this way, a common metric may underlie multiple evaluations and will substantially enrich the interpretation of PROs scores.”

More precision for patients

Given the fact that PROs are engineered with such a patient-centric focus in mind, they, by their very nature, follow the same methodology as the wider precision medicine movement and as such could easily work cohesively with other personalised clinical approaches.

Dr Martinez strongly believes this to be the case: “I completely agree with the notion that PROs are well aligned with precision medicine – possibly even better than other approaches most frequently associated with the concept, such as genotyping. Whereas the latter may facilitate a stratification of the patient groups based on biological characteristics, PROs are unique in that they assess the individual integration of the outcomes of health status and healthcare. Tempting as it may be to present them as the ultimate outcomes of care, they are best conceptualised as an essential measurement, along other measurements which also determine other relevant outcomes, such as mortality and complications.”

Turner also agrees on the value of this harmonised approach, stressing flexibility of application as a key strength: “PROs complement and enable individualised and patient-centred healthcare. PROs are collected for a wide variety of purposes and can be used at all stages of treatment from screening to ongoing monitoring and treatment decision support. There has been a rapid acceleration in electronic data capture within healthcare; through embedding PROs in routine electronic data collection, there is further potential to use PROs to enhance patient-centred care through real-time monitoring and early identification of problems.”

While the benefits of the PRO are promising indeed, it can be argued that, perhaps due to its relative infancy, the tool still has a long way to go. While the applications are already vast – and the list is growing – the tool’s usefulness is somewhat limited by its lack of prevalence throughout general practice, with many professionals not familiar with how it works or what value it can provide. This presents a definite challenge in the coming years as awareness and training must be provided to adequately reap the evident benefits of the PRO, particularly in some of the less obvious areas of application.

“Policy makers are particularly interested in considering the use of PROs in the evaluation of the performance of healthcare systems and providers and their benchmarking, with the aim of stimulating change in the behaviour of health professionals,” Dr Martinez tells us. “In the absence of daily experience of using PROs to support decision-making, health professionals are ill-prepared to respond to this challenge.

“The immediate frontier for PROs is therefore their routine implementation in clinical practice for supporting shared clinical decision-making,” he continues. “There is good evidence from scientific studies that the routine use of PROs can change some aspects of healthcare providers’ behaviours. The evidence is not conclusive for improving health outcomes, but there is still a steep learning curve in our understanding of the best systems for implementing routine data collection, interpretation and feed-back of PROs in clinical practice.”

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