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The PROs and cons of pushing patient centricity

Published on 08/01/18 at 11:06am

As the pharmaceutical industry places increasing weight on the importance of patient-reported outcomes in securing approvals, Ben Hargreaves examines how this relationship can be mutually beneficial.

Patient centricity became the key buzzword for pharma companies during the last decade. It was used in many different contexts, from who to deliver medicines to, to how to perform clinical trials, and generally how to orientate business models. With the rise of disruption across businesses that aim to offer the consumer convenience as a starting point, from the upheaval of the traditional high street retail chains by Amazon to the revolution of how people hail a taxi by Uber, people now simply expect more from the companies whose products they use.

The healthcare sector should appear to be distinct from this type of consumer-driven angle, with patients traditionally approaching a doctor for advice, who then makes a judgement to the best of their ability and provides a corrective or palliative treatment, where possible. It means that medicine was always built upon a reliance of an authority figure who knew best – no further questions were needed.

Ask any doctor currently working in a higher-income country whether patients now uniformly hold such a respect for their knowledge, however, and the answer is likely to be negative. Patients are now able to self-diagnose through the use of search engines, able to compare their experiences of differing medicines on message boards and have a greater ability to vent their frustrations via social media. It means that patients are now more often likely to question a diagnosis, query the choice of medicine and demand treatment where perhaps none is necessary.

All this makes patient treatment sound like an overbearing challenge – in reality, the patient’s desire to vocalise their condition and to be able to truly engage with a system that was once paternal rather than collegial is now finding a natural equilibrium. If a patient can be given license to mention symptoms that are not being treated by their current medicine then there is the opportunity to improve their quality of life by prescribing a drug to alleviate that. If a patient is suffering a side-effect from a medicine that is unwanted, it offers an opportunity to look at taking action to mitigate it or avoiding it altogether by changing medicine. From a developmental perspective, it also allows pharma companies to be aware of, and react to, unwanted reactions to drugs, as well as highlighting the strengths their own medicines possess.

Further than this, it offers the potential for the pharmaceutical industry to listen to feedback to better understand what treatment outcomes are important to their patients. This means that secondary endpoints can also include improvement in the quality of life for patients, on top of condition-outcomes.

Patient engagement: More than just noise

The FDA was early to recognise the importance of patient voices in the design and implementation of clinical trials. In September 2015, the US regulator set up the Patient Engagement Advisory Committee that actually met for the first time during October 2017. Patients were given the opportunity to provide input on clinical trials for medical devices. The group is made up of patients and patient advocates, allowing for the recipients of medical innovations to have their own say on what is regarded as important.

Of considerable significance for the committee was to bring patients into regulatory discussions, allowing the patient voice to provide input on clinical trial design; patient recruitment, enrolment and retention; and the communication to patients during, as well as after, the trial.

In a blog post on the announcement at the time, Nina Hunter, Associate Director for Science Policy, wrote: “We are entering an era of ‘patient-centred’ medicine in which patients and their care partners participate actively in decision-making and priority-setting about all aspects of health care. Americans are becoming increasingly active consumers of health care, making choices about their doctors, diagnostics, treatments, and healthcare experiences rather than simply allowing health care providers to make the decisions for them. Moreover, FDA believes that patients can and should bring their own experiences to bear in helping the Agency define meaningful benefits or unreasonable risks for certain new devices.”

Beyond this particular development, another idea of opening a new Office of Patient Affairs has also been mooted at the FDA, showing just how far the ‘buzzword’ of patient-centricity and engagement has snowballed into practical steps.

As regulatory bodies take patient voices more seriously and they begin to carry more heft, pharmaceutical companies have realised that working with patients to produce their feedback on medicine can provide their treatment with more weight when they are to be considered in-front of HTAs.

For instance, highlighting the growing importance of patient-reported outcomes (PROs), Jeffrey Shuren, Center for Devices and Radiological Health Director, noted that the agency has seen a substantial increase in the number of clinical trials including PROs: "Over a five-year period we saw an over 500% increase in the number of pivotal clinical trials for premarket approval applications that used patient-reported outcomes, and now over 50% of our PMAs [professional medical associations] include patient-reported outcome data”.

Finding concrete benefits

This is because PROs offer benefits in a number of ways that are often not immediately obvious. For instance, a study published in the European Medical Journal examined the relevance of PROs in the management of inflammatory bowel disease (IBD), finding that there was a direct correlation in the amount of feedback the patients were able to provide and disease-outcomes.

The succinctly titled study, ‘Relevance of Patient-Reported Outcomes for the Management of Patients with Inflammatory Bowel Disease’, began with the premise that providing more opportunities for the patients to engage would help circumnavigate an issue with disease management: patient adherence.

IBD is a chronic condition and, at present, the best that can be offered are treatments that minimise the effects of the condition. Many patients can grow frustrated with taking the medicine and any measures to improve this could be beneficial to physicians, patients and the companies behind the medicines.

The study noted: “Increasing patient knowledge and understanding of their medication may work to improve their adherence. A study analysing patients’ suggestions to improve their current treatment found that 54% of patients would like more information regarding new medications and 50% would value a closer collaboration with their physician.”

Further than this, the study pointed out that patients may often be better placed to determine their own symptoms and able to aid physicians more effectively in the kind of treatment offered to them.

The study continued: “PROs do not always correlate with the physician’s view. Evidence has shown that physicians often underestimate the severity of a patient’s illness, report fewer problems than patients, and overestimate the improvements of treatment. In order to improve the value of PROs, physicians must engage patients in their disease management, otherwise known as patient empowerment. Empowerment can improve treatment success.

“As it is becoming clearer that empowered and informed patients who are able to have a role in the decision-making have better outcomes, PROs will not only have further impact on the management of patients with IBD but also on health technology assessments and healthcare payer decisions.”

Taking practical steps on PROs

One pharmaceutical company that has begun using PROs consistently within its own clinical trials in the IBD space is Takeda. Pharmafocus reached out to learn more about its feedback on why it had begun employing strategies to gather more PROs and what the benefits had been.

Mona Khalid, Senior Director, Head of Evidence & Value Generation at Takeda, explained how the company’s work in the area had developed and what practical steps it has taken to gather more PROs:

“Takeda places a high importance on PROs, and has dedicated teams working on the study of and creation of new tools to capture these outcomes. We are trailing new technologies to facilitate the collection of PROs, such as through wearables.

“In September 2016, we launched a pilot digital technology programme with Texas Digestive Disease Consultants and Vanderbilt University Medical Center to support patients and physicians with the management of inflammatory bowel disease (IBD). The pilot project, iBData, is designed to intersect healthcare and digital technologies and will allow patients with IBD to track their symptoms and lifestyle factors with wearable technology. In this project, approximately 100 people with IBD are using a special wearable device to track their symptoms and lifestyle factors. The data will be collected and translated into reports intended to help enhance patient-physician interaction with the goal of improved care.”

As previously mentioned, Takeda has a portfolio within IBD and has used PROs to engage with patients. Khalid detailed how the PROs have effectively backed up clinical findings, providing them with patient-substantiated evidence to take forward to HTAs.

“IBD is a life-long, debilitating disease. Through the collection of PROs, we have shown that Entyvio (vedolizumab) has meaningful, positive impact on patient’s health related quality of life through validated tools, such as the Inflammatory Bowel Disease Questionnaire that captures changes to symptoms and daily life impact.

“We have also shown that these effects are maintained over longer time periods, over the course of years. These findings are consistent with the body of real world evidence that we have seen to date with data that are collected directly from patients who receive Entyvio in clinical practice.”

In terms of the increasing importance of how PROs are received by HTAs, Khalid stated: “Regulators are interested and see value in how patients feel, function and survive in addition to ensuring the endpoints we develop are consistent in capturing intervention benefits in the same way. We also partner with organisations such as International Society for Quality of Life Research, examining ways to capture the patient voice with a view to discuss the inclusion of these endpoints in studies with regulators.”

Regarding the overall importance of drawing together patient feedback on their experience with treatments, as well as the importance of improving the overall process for the patients undergoing clinical trial treatment, he noted:

“Patient feedback is critical both in terms of experiences when participating in our studies, and also with respect to understanding the effect of interventions and how this impacts the patient directly. This is important in informing patients and clinicians on PROs such as symptoms, health-related quality of life, perceived health status and the impact that a new treatment may provide in each of these regards, especially in chronic conditions such as IBD.

“We believe it is vital to seek patient feedback to optimise our studies to help facilitate patient participation, in addition to seeing the value in how PROs can improve the quality of patient care by creating a holistic approach to clinical decision-making.”

On the other side of the debate, Khalid did mention that difficulties are still faced in the process of gathering such data: “Key challenges include adequacy and timeline to development to support product claims. Additionally, if the tools designed to capture PROs are not designed and used adequately, it may be difficult to draw meaningful conclusions.”

Capturing ‘soft’ data

The latter point offered by Khalid is one particularly significant downside to PROs that has been known about from the beginning – they are ‘soft’. By the use of that term it is understood that the data that is gathered through PROs are entirely dependent on the patient’s subjective experience. Compared to other trial data, such as whether treatment has empirically had an impact on disease progression, for instance. However, it is not so cut-and-dried when it comes to an individual’s experience of their own symptoms or their reaction to a medicine.

On top of this are two greater barriers to implementation, which come in the form of technological and operational challenges thrown up by the demands of PROs. As attractive as the idea may be of throwing patient’s weight behind a drug application, the process is not a simple one for those running clinical trials.

The additional data supplied by the patients has to be efficiently processed, which means electronic data collection. This leads to all kinds of storage hurdles, as well as more basic requirements, such as patient portals where data can be submitted. All of the data must also be collected in a manner that makes it easy to call on for submission to relevant authorities, and be compliant with data protection. It must also be user-friendly and, more importantly, error-free – the extra burden placed on patients and those collecting the data cannot be exacerbated by glitches to the system, or risks having everyone involved rapidly lose patience.

This leads directly on to the second major issue with such data collection – the time required. Clinical trials are notoriously time consuming and every delay is extremely expensive, with one study by AppliedClinicalTrialsOnline calculating that a one-day delay can cost a company approximately $1.3 million. Everyone involved in the process (patients, staff and clinicians) need to be ready and prepared to take time from their day to process the data required – a hard-sell when patient retention to clinical trials is relatively low already due to the time burden, with the average dropout rate, according to Forte Research, residing at 30%.

PROs set to rise

Despite these challenges, there is little doubt from within the industry that patient-reported outcomes will be collected in greater volume and will be more often moving ahead. A study by Tufts Center for the Study of Drug Development revealed that 93% of respondents to its survey said they were aiming to use electronic PROs in the next three years. At the moment, however, the study also revealed that ePRO data only makes up about 3% of all data types collected in electronic data capture systems.

Nevertheless, at the larger companies, there is a greater emphasis placed on collecting PROs during clinical trials. Researchers from Cutting Edge Information found that 68% of clinical trials conducted by the big pharma companies utilised PROs.

Victoria Cavicchi was one of the research analysts behind the findings; she noted a sound of caution about placing too much importance on PROs in regulatory filings: “Although PROs are increasingly embraced in the pharmaceutical industry, life science organisations must not rely solely on these measures to support regulatory approval […] Teams should play a balancing act and incorporate the right mix of traditional clinical evidence with patient responses to build the strongest case for emerging products.”

This cautioning of moving too quickly is sensible but the pharma industry has never been one to move too quickly ahead in the face of new technologies. There are other areas in the life sciences and healthcare industries that are keen to forge ahead because innovation can potentially reduce the workload burden.

It may seem counterintuitive but doctors are beginning to find uses for PROs that actually reduce workload – counterintuitive because individuals within healthcare systems across the Western world are suffering under the onus on data collection. This can lead to a huge amount of time filling in paperwork that often feels inefficient compared to actually engaging with patients.

Several methods of using PROs have been developed that actually streamlines the process of engaging with patients, allowing for time to discuss the areas or symptoms of conditions that are actually most important to the patients. This has led to doctors working with electronic programs that allow patients to fill in and submit PRO questionnaires prior to appointments, allowing the patient to signpost the priority areas that they would like to effectively manage. This means that physicians can engage with patients whilst having a prior repository of knowledge to guide these interactions, leading to better outcomes for the patients and more time saved for the doctor.

In areas such as depression, or in those suffering from conditions associated with a high-risk of this, it has allowed PRO questionnaires to be used to identify patients who may be at an increased risk of suicide. The answers to the questionnaire that show a particular pattern can be flagged for those at-risk, and consultation can be guided accordingly.

Driving research and improving medical care

One organisation that is helping to collect PROs on a larger scale is Corrona, a US-based provider of disease registries. The organisation has worked to build large-scale databases on a number of diseases and recently announced its collaboration with the US National Multiple Sclerosis Society. Pharmafocus contacted a spokesperson for Corrona to learn more about what the partnership would entail, as well as what the long-term plan is for the collection of PROs:

“The collaboration builds on the strengths of each member. Corrona has successfully launched registries, collected data, and performed analytic research on the datasets for over 16 years. While our experience lies with the registry, the National MS Society will assist with increasing the exposure of the registry to neurologists, patients, and pharma through targeted efforts to its members, practicing neurologists, and other stakeholders. The National MS Society will be able to conduct research in the registry utilising Corrona’s biostatisticians and epidemiologists.

“The registry is designed to be a long-term follow-up. The recruitment and follow-up will continue indefinitely. We expect the Corrona MS Registry to be the largest registry of its kind in the US. We say this for two reasons: first, we believe there is a need for greater real world evidence to better guide prescribing decisions in MS; second, Corrona has a track record of successfully launching five other registries, and has deep experience in how to successfully scale a new registry.”

When asked about what the potential benefits offered by the collection of PROs from patients, the spokesperson stated:

“Corrona’s primary mission is to advance medical research and improve the quality of patient care. These data can be used to research areas such as pharmacovigilance (drug safety), pharmacoeconomics, and drug utilisation. Corrona utilises several methods to get information out to the both neurologists and patients, including poster/abstract presentations at national/international conferences and newsletters to sites.

“Corrona was founded in 2000 by leading rheumatologists dedicated to advancing and improving the care of patients with rheumatic and other chronic diseases. Since then the company has expanded from rheumatoid arthritis to other rheumatic diseases (psoriatic arthritis and spondyloarthritis), dermatological disease (psoriasis), gastroenterological disease (inflammatory bowel disease), and now neurologic disease (multiple sclerosis).

“In the short term, all of our registries have provided meaningful information. However, the power of what the registry data can tell us increases dramatically over time. In the short term, we are able to provide detailed information about the patterns of treatment and the burden of a particular illness in terms of clinical measures and important patient-reported measures like pain, fatigue, and work productivity. In the longer term, Corrona can provide information to help guide which patient should receive which therapy and evaluate long-term safety.”

The way in which Corrona is collecting PROs then stands as a marked difference from the way that the data is employed in clinical trials in that, rather than looking to the short-term benefits medicine can give to provide to regulatory authorities, the registries look to longer term measures of the impacts of treatment on a patient-level.

In the future, this could provide important feedback for both physicians and to pharmaceutical companies about how patients are being managed by various treatments. Looking towards the future, Corrona’s spokesperson spoke on the potential in the years to come and also the current challenges they face gathering the data:

“Corrona is excited about the prospect of exploring new ways to capture and integrate patient-reported outcomes into our analyses. In particular, we look forward to smartphone apps and other devices making the capture of this information simpler and less burdensome for patients.

“With any long term follow-up registry there can be questionnaire fatigue that sets in over time. We address this with newsletters (and other engagement efforts) to inform the patients on how their data is helping contribute to the larger research.”

The potential for PROs is still relatively untapped, but the final note by Coronna that one of the significant challenges is keeping patients engaged with supplying the data required to make PROs work will always be a challenge no matter how far technology progresses.

Seeing the difference

Corrona has already pointed towards one way of making sure that patients stay engaged enough to continue providing their feedback – by ensuring that they can see the difference they are making. This will be the key challenge that will have to be met by the pharma industry and by the healthcare organisations that look to, or continue to, employ PROs and leads fully back to another key buzzword often paired with patient centricity: ‘patient engagement’.

Of course, PROs are actually one form of patient engagement, but if the wider goal of patient engagement is to place the patient’s voice at the front and centre of healthcare discussions then the approaches need to be tied together. Wider patient engagement measures often reside at the cutting edge of technology, to include tools such as smartphone apps, smart watches and social media. Informing PROs with such approaches could reduce the burden placed on patients, identified by Corrona as one of the biggest barriers. For example, an app with which patients submit PROs is one potential avenue to follow, as is Takeda’s method of collecting data through wearable technology. As tools becomes increasingly sophisticated, patient engagement is becoming easier and increasingly capable of providing feedback of significance to the pharma and healthcare industries – it up to the industries themselves to take advantage of this.

A recent study by the National Quality Forum, alongside patient community PatientsLikeMe, found that PROs were often asking questions that patients did not fully understand or were not always accessible for patients. Regarding the findings, PatientsLikeMe Co-founder and President Ben Heywood said: “Patients are the ultimate stakeholders in their care and their health, so it’s critical to know what they need and value most.” Heywood’s assertion that patients are the ultimate stakeholders is one worth bearing in mind and one factor that is rapidly become increasingly important as patient centricity continues to move beyond being just a buzzword.

Ben Hargreaves

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