Crowdsourcing Initiatives

In addition to these prediction initiatives, biopharmas are adopting new crowdsourcing models. For the epilepsy community of approximately 65 million people worldwide and more than 2 million in the United States, UCB staged in April 2015 in Brussels and Atlanta a “Hack Epilepsy” event, where digital experts, specialists, and patients collaborated on building digital tools to inform patients, empower them to talk about their illness, and guide them with questions to providers, following a diagnosis. These events delivered 17 prototype digital solutions, half of which continue in development with startups and UCB support [7].

Patient Insight Research

Uncovering patient needs at early research stages entails technical and legal issues across countries. Data privacy regulations, cultural traits, and digital channel preferences, from smartphone apps to text messaging, vary across regions. There is a need for a comprehensive patient engagement platform, whereby messaging, electronic collection of patient-reported outcomes, health apps/wearable connections, and call center escalation should be coordinated, secured, and proven through global experience [8].

As research moves in to the clinical stage, patient-reported outcomes (PROs) are broadly used, but some gaps remain. The FDA has issued guidelines on the development and validation of PROs, and they are included in some drug labels and observational studies. However, they are not necessarily patient-relevant. Experience in areas such as mobility, cognition, pain, and sleep may not be captured adequately; for example, sleep may be more important to Parkinson's patients than tremor or limb rigidity, and in psoriasis, itchiness may matter more than lesion characteristics.

The understanding of patient experience is most extensive in the small populations of rare diseases. For instance, Shire has established PRO groups to optimize consultation with patient organizations. Even in the large diabetes populations, Novo Nordisk has a long experience of patient engagement, works with regulators to develop PRO tools to optimize quality of life, and conducts cross-disciplinary studies of behavioral and perception challenges in diabetes management [9].

A landmark initiative was announced in July 2016 by the National Institutes of Health (NIH) as the Cohort Program, within the national Precision Medicine Initiative. This longitudinal effort aims to engage one million or more US participants to improve treatment and prevention, based on individual differences in lifestyle, environment, and genetics. Data will be collected through health histories, genomic information, EHRs, and mobile devices, and participants will have ongoing input into study design, as well as access to individual and aggregated results. The program will fund a network of health systems operated by the Veterans Affairs Department to organize enrollment, with initial participation including Northwestern University, Columbia University, and the University of Arizona. It will also support a Data Center (awarded to Vanderbilt University, the Broad Institute, and Verily), as well as a Participant Technologies Center, whereby the Scripps Research Institute and Vibrant Health will create digital enrollment tools. The initial focus will be on genomic testing and next-generation sequencing [10].

Rare Disease Trials

Rare diseases are now a major focus, numbering over 7,000, with only 10 percent having treatments, and they represent a major opportunity, with estimated worldwide sales of $176 billion by 2020 [11]. However, trial difficulty and cost are highest in this area, since it can be hard to find participants and lead investigators, as well as to organize transportation—sometimes across borders—for patients and their families. For rare disease–focused companies like Sanofi Genzyme and Shire, the first step may be a natural disease history study, through advisory boards and individual conversations; this may help establish which biomarkers, protocols, and endpoints best reflect patient needs. Advocacy groups may also have registries that enable patient identification. To optimize collaboration, companies should create an engagement framework with all relevant functions, from medical affairs, legal and regulatory to commercial; they should build close relationships with key opinion leaders trusted by patient groups, and encourage collaboration between these groups, as several may be active within a specific disease area.

The trade-offs in rare diseases may be the prospect of smaller and faster trials, the incentives of the Orphan Drug Act, and the market potential of many diseases with no treatment, versus poorly understood etiologies, complex diagnoses, difficult recruitment, and increasing payer pressures and public outcry regarding ultra-premium prices.

Trial Recruitment and Retention

Even in diseases with larger populations, enrollment is challenging, as protocols may discourage patients due to the frequency and length of trips to a research center, and as inclusion/exclusion criteria have multiplied. While advocacy groups can help, up to half of rare diseases do not have a specific foundation. In response, companies such as Sanofi Genzyme may help establish and support patient groups and develop networks of investigators and specialized medical centers.

An added challenge is the representativeness of patient KOLs. The most engaged and visible e-patients may be younger and more educated than a general disease population. This concern about tokenism may be partly overcome by stratified recruitment and by a combination of patient inputs with real-world data sources, including medical claims and EHR records [12].

As patient retention is also an issue, predictive analytics (see Chapter 10) may help track demographic and behavior profiles for participants who stay in trials, and time-related burdens may be minimized with simplified consent forms and streamlined visits to research centers.

An underused incentive is feedback to patients about study results, as these are often not communicated or interpreted. This two-way dialogue can take place through in-trial surveys, ongoing advisory panels, and protocol and endpoint codevelopment. Trial optimization may be conducted through sequential steps:

• At the protocol design stage, use large data sets to verify eligibility and inclusion/exclusion criteria, and identify recruitment drivers and barriers (study logistics and frequency of invasive examinations versus burden of symptoms and acceptance of risks to achieve better outcomes).
• At the start of the study, use social listening to identify areas of special patient interest as well as chief complaints.
• During the study, to improve coordination, communicate key patient attitudes and concerns to researchers.
• After the study, ensure that patients have access to study results as well as to their interpretation [13].

Patient-Reported Outcomes

Since the 2009 FDA Guidance on PROs to Support Labeling Claims, these have increasingly been included in trials, especially in oncology, where symptoms such as fatigue, weight loss, and pain have a substantial impact on quality of life. Another PRO driver is the reliance of payers on real-world evidence to support reimbursement, and the role PROs can play in comparative drug effectiveness. This extends to Europe, where the EMA now requires input from patient advocates, as it has direct value for drug tolerability, delivery formulation, and titration. However, a 2016 study showed that only 7.5 percent of reported trials from 2010 to 2014 included a PRO, whereas 24 percent of earlier trials had one.

This may be related to more rigorous standards of review from regulators, as well as a slowing of drug approvals by using PROs to continually adjust dose regimens according to reported side effects [14]. There have been exceptional cases of inclusion of PROs in labels, such as Incyte's Jakafi (ruxolitinib), approved in 2014 for myelofibrosis, where symptom information was included on the label for FDA approval.

Payers also have mixed views on the application of PROs in practice. Medical directors may see engagement as appropriate only in Phase III, whereas pharmacy directors may be divided on all phases. While medical directors are outcomes-driven, pharmacy directors are accountable for budgetary impact and may be more open to patient views of comparative effectiveness.

Another channel for PROs is patient registries; these could be especially useful at the Phase IV post-approval stage, to document the impact of different dosage and titration cycles, and to decide on other treatment regimens than the one already approved. However, patient registries are not generally accepted as evidence to support an FDA label ruling [15].

Clinical trial enhancement and the broader use of patient-generated data are part of the objectives of online patient communities such as PatientsLikeMe.

The role of observational studies remains controversial. Several publications have focused on “eParticipants” who engage in social media during randomized trials, addressing the potential to undermine their integrity on topics such as eligibility (mutual coaching on how to meet criteria), blinding (advice on how to determine the treatment arm), and safety (sharing adverse effects may stimulate other patients and lead to a false spike in these reports). For instance, during trials for Incivek (telaprevir) from Vertex for hepatitis C, participants had online discussions on sites such as medhelp.org. These included sensitive issues such as suggestions to identify in which study arm patients had been assigned [16]. Forum participants can also pose as self-appointed medical experts and provide advice on dosing, safety, and efficacy, list symptoms that may not be drug-related, and suggest nonadherence.

Preventive measures may include:

• Assessing the size and degree of activity of online communities
• Complementing PROs with objective data from sources such as EHRs
• Educating participants on discussion risks as early as on the informed consent form and through organizations such as the Center for Information and Study on Clinical Research Participation.

In sum, patient centricity strategies in R & D include external and internal processes.

• Externally, gather patient insights on unmet needs early in discovery, through in-person discussions and advisory boards. Also, work with patient groups for recruitment and collect data from multiple sources. In phase IV studies, continue to track the patient experience and provide education and clinical and economic support.
• Internally, analyze at an early stage the natural disease history and drive development with real-world evidence. Facilitate recruitment with simplified consent forms and codevelop protocols and endpoints, which should be reassessed according to PROs. Finally, continue in Phase IV with adherence and access programs. This dual process is shown in Figure 6-3.

Patient Satisfaction Ratings

Ever since the first US News & World Report “best hospital” rankings in 1990, based mostly on physician surveys, rating methods have multiplied, from the launch of Healthgrades in 2004, Medicare's Hospital Compare in 2005, hospital ratings by the Leapfrog Group and Consumer Reports, and the ranking of 16,000 surgeons by ProPublica in 2015. Crowdsourced ratings such as Yelp's were found to generally correlate with those of the federal government HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) survey, launched in 2006. The HCAHPS scores drive 25 percent of the financial incentives in the Medicare value-based purchasing program. These surveys are systematically fielded and interpreted, but they suffer from low response rates, entail delays between hospitalizations and public reporting of results, and rarely identify actual problem sources. By contrast, ratings on social media sites are unstructured and have largely uncurated narrative reviews.

In the United Kingdom, the National Health Service operates the NHS Choices site, allowing structured patient reviews. Consumer-generated reviews on sites such as Yelp contain several domains important to users that are not included in HCAHPS, such as cost of hospital visit, insurance/billing, and quality of nursing and staff. While HCAHPS asks, “How often did doctors/nurses treat you with courtesy and respect?,” Yelp allows more complete narratives. In response, several health systems have begun allowing direct patient reviews on their sites. Consumer platforms suffer from selection bias and possible false reviews, but they retain the advantage of ease of use and real-time reporting [19].

Even government ratings of hospitals remain controversial. When the Centers for Medicare and Medicaid Services (CMS) released its star ratings in July 2016, the American Hospital Association criticized its confusing format. CMS admitted limitations such as the fact that specialized services including cancer care were not rated, and that measures of deaths and readmissions were based on data from Medicare beneficiaries only [20]. The methodology could also put academic medical centers at a disadvantage, as they treat more complex cases and poorer populations.

Other issues include the lack of a common definition of “patient satisfaction” among the various ratings instruments and the fact that consumer reviews focus on service components of care, such as staff courtesy, that are not correlated with accepted outcome measures such as mortality and readmission rates. Optimally, these two types of measures could be combined, as well as the following steps:

• Public education about the objective components of quality
• Measurement of clinical results that consumers can understand, such as complications and outcomes from surgical procedures
• Inclusion of consumer participation in HCAHPS ratings
• Building into EHRs the capacity to include PROs
• Combining patient experience results, quality metrics, and cost information, and using this more broadly in composite measures [21]

Physician/Patient Dynamics

While there has been significant progress in provider/patient communications, there remain substantial disconnects. The AHRQ defines patient engagement as a set of behaviors by health professionals, a set of organizational policies, and a set of individual and collective mindsets that foster the inclusion of patients and their families as active members of the care team, encouraging partnerships with them, their providers, and communities [22].

To bridge the disconnect between what the patient knows and what the provider thinks he or she knows, shared decision making (SDM) aims to support patient-centered care with these core attributes: education and shared knowledge, involvement of family and friends, collaborative team management, sensitivity for nonmedical/social dimensions of care, respect for patient needs, and free flow and accessibility of information.

In February 2015, CMS approved reimbursement for lung cancer screening with a mandated shared-decision counseling session before the first scan, to determine risks and benefits. Among others, the Mayo Clinic has set up online forums hosting discussion groups, blogs, and events, and providing a non-acute physician/patient platform [23].

In a 2016 NEJM Catalyst online survey sent to clinicians and healthcare executives, respondents saw engaged patients as adhering to a care plan co-created with providers and taking an active role in improving their health. The biggest challenge cited was insufficient time with patients. A majority found patient portals helpful, but there was not strong support for remote monitoring, due to concerns about the burden of handling data streams, and beliefs that, without engagement, technology alone was unlikely to change behavior [24].

Other studies have confirmed communication deficiencies. The 2016 Patient Access and Engagement Report by the nonprofit CancerCare included six surveys with input from more than 3,000 cancer patients, from newly diagnosed to post-treatment. Overall, fewer than half of respondents discussed the cost of follow-up testing with their physicians, only about two-thirds had adequate information about treatment benefits and risks, and only 13 percent felt sufficiently informed about clinical trial opportunities. Fewer than half obtained a second opinion about their treatment plan. Strikingly, communication gaps extended to payers. Only about one half of respondents reported understanding their health plan coverage, despite 58 percent feeling distressed about the financial burdens during treatment [25].

While a broad portfolio of digital engagement tools is available, these generally need further development. Patient portals are most widely used but lack real-time interactivity with providers; patients can access test results but do not have their interpretation in real time. Mobile appointment scheduling is useful, but reminders may be perceived as intrusive. E-consultations provide faster access to care, but have limited applicability, and “doctor on demand” virtual services may vary greatly in quality. Wearables allow continuous data monitoring but without interpretation or connection to medical records. Social networks provide peer-to-peer information and support, but entail potential privacy and security issues. These benefits and limitations are shown in Figure 6-4.

Some health system initiatives now aim to optimize their patient experience with a new organization. Faced with a gap between its good ratings on medical outcomes and uneven patient experience reports, in 2007, the Cleveland Clinic adopted a new care model, creating institutes with multidisciplinary teams treating a single organ system, such as heart/vascular. A new Chief Patient Experience officer position was also established, and outcomes data were published on every surgeon and program, in addition to the HCAHPS ratings available online to consumers. “Managing the 360” defined the patient experience as everyone and everything people encountered, from their decision to choose the clinic until they were discharged. A “Best Practices” department within the Office of Patient Experience identified successful approaches and tested new practices in pilot projects. A same-day appointment option was mandated for the first time among major US health systems. The full program was launched in 2010, and by 2013, a CMS survey showed that the Clinic was in the 92^nd percentile for patient satisfaction, among the 4,600 hospitals surveyed [26].

Biopharma Initiatives for Engagement

Biopharmas have greatly expanded patient communications, but they still face broad distrust among consumers. Traditional direct-to-consumer (DTC) promotion runs against ad-blocking behavior and disruption concerns, especially on mobile channels. While sites such as Fit2Me, launched by AstraZeneca in 2014 to reach the nearly 30 million Americans with type 2 diabetes, offer a wide range of customizable diet and exercise tools, the Fit2Me drug information remains limited to the company's own products, unlike health system sites such as that of the Mayo Clinic.

A 2016 study by researchers at the FDA Office of Prescription Drug Promotion and RTI International focused on 65 oncology websites and found that, while drug benefits and risks were almost equally represented, both consumer and professional sites had uneven quantitative information for benefits and risks [27].

While biopharmas have sought to simplify patient outreach with structures like Shire's OnePath program, assigning a personalized care manager as a single contact point for care coordination and drug access, there is very low consumer awareness worldwide of the range of available patient services.

A 2015 Accenture survey of 10,000 patients in Brazil, France, Germany, and the United States, across seven therapeutic areas including the brain, bones, heart, immune system, metabolism, and oncology, found that only 19 percent of responders were aware of services from biopharmas. They especially wanted more guidance at the pre-diagnosis stage, to know their potential risks before experiencing symptoms. They also wanted a single point of contact for information, and 85 percent preferred it to be their first-in-line team of healthcare professionals; only one percent saw biopharmas in that role [28].

This points to a related need to expand the biopharma/physician range of communications. A ZS Associates survey of physician access by salesforces found that only 44 percent accepted more than 70 percent of sales calls, versus nearly 80 percent in 2008. While a large part of budgets was still focused on the salesforce, more than 53 percent of activity took place through nonpersonal channels such as emails, mobile alerts, and websites. One factor leading to better access was the launch of a truly novel therapy, such as new hepatitis C drugs for gastroenterologists, or oral anticoagulants for cardiologists. These studies suggest that salesforces need to break out of their silos and work with marketing and patient advocacy teams to expand the range and depth of education materials and to communicate these to broader audiences, including nurses and physician assistants, as they are also often more accessible [29].

In sum, patients are at the center of multiple points of care with varying degrees of connectivity. Education channels require health literacy, which remains uneven across geographic and demographic populations. Public health communications include ratings such as HCAHPS scores, still inadequately understood by consumers. Online communities are successful with information, support, and even financing of some trials, but they face privacy and security issues. Health data are more easily quantified through wearables but lack connections to medical records. Biosensors are optimizing remote drug monitoring by biopharmas, but these firms need to communicate more broadly the range of their “beyond the pill” services. This communication ecosystem is shown in Figure 6-5.

Drivers and Barriers of Behavior

A full understanding of the patient journey requires gathering insights from multiple sources about the drivers of behavior at each step and setting up goals linking value added to the patient and value to the company. This includes increased awareness and screening, better trial recruitment and retention, increased prescribing and fulfillment, reduced switching, and improved adherence. Defining metrics requires coordination between R & D, medical and corporate affairs, health economics, sales, and marketing functions.

There should also be a recognition of barriers at each point of the journey: Initial misconceptions about the condition, decision to seek alternative advice and treatment after diagnosis, abandonment due to side effects or burdensome self-management for multiple conditions, logistical issues, language and cultural barriers, and total cost burden. The intensive continuous coaching that is needed may be outsourced in part. Employers and payers may partner with companies like Omada Health, with services such as professional lifestyle coaches.

The understanding of behavior drivers and barriers may vary across diseases. In the case of depression, a survey of more than 1,200 patients showed that 71 percent took over a month to receive a diagnosis after their first awareness of symptoms, and 38 percent took more than six months. Although antidepressants may take 6 to 12 weeks to be fully effective, the survey showed that 18 percent of prescribed drugs were discontinued in less than one month, with perceived lack of efficacy as the reason for 52 percent of respondents [31].

Given the consumer preference for a healthcare professional as a primary contact point and regulations in some jurisdictions that restrict direct contact with patients, biopharma companies should strive to build high-credibility partnerships with providers and to develop with them online and offline care management tools.

The value proposition for a biopharma then depends on its therapies, services, and provider alliances; it is specific to subpopulations with the most needs based on socioeconomics and disease state; and it is customized to significant moments in the journey, in order to achieve outcomes measures of quality, cost, and patient satisfaction [32].

Adherence Strategies

Adherence can be defined as the extent to which a patient behavior, including taking medication, following a diet, exercise, or other lifestyle actions, reflects agreed-upon recommendations from a healthcare provider. Nonadherence has long been known as having serious health and cost consequences. Studies have shown that 20 to 30 percent of prescriptions are never filled, and that about half of medications for chronic diseases are not taken as prescribed. In the United States, nonadherence is estimated to cause at least 10 percent of hospitalizations, with an increase in mortality and morbidity, and to cost the healthcare system between $100 billion and $289 billion annually [33]. Adherence is a multifactorial behavior that is driven by socioeconomics and demographics, patient knowledge and attitudes, condition and treatment status (disease severity, treatment complexity, and side effects), provider traits (communication skills and resources), and cost issues (drug coverage, co-pay, and access to medication and reimbursement support).

A study funded by the AHRQ found that the effectiveness of interventions varied across diseases. Generally, for chronic diseases, interventions with behavioral support, through continued patient contact over several weeks or months, were most effective for hypertension, heart failure, and hyperlipidemia; other approaches included reminders and pharmacist-led interventions. For depression, collaborative care with in-person visits and counseling appeared effective [34].

Optimizing adherence thus entails both strategic and tactical approaches. Strategies include partnerships with health systems, employers, payers, and pharmacies, as well as alliances with advocacy groups to share experiences and track treatment effect and outcomes. Tactics range from the development of point-of-care tools to nurse-staffed call centers and clinical educator programs for disease management and treatment monitoring. For example, Philips' HealthSuite digital platform has integration capabilities with EHRs and, through a collaboration with Validic, consumer data from wearables. Validic has also partnered with the Sutter Health system of 30 hospitals in California to develop a preventive model of care, including a hypertension management program connecting with blood pressures monitors and activity trackers [35].

However, issues remain at the consumer end, including quality and privacy. A 2016 study published in JAMA Cardiology compared the accuracy of four wrist-worn heart rate monitoring devices with that of traditional chest-band electrode systems. While the Apple Watch reached a 91 percent accuracy, other devices, including the Fitbit Charge HR and Basis Peak were, respectively, only 84 and 83 percent accurate, versus 99 percent for the Polar H7 chest band device. Accuracy diminished with exercise intensity, with Fitbit underestimating heart rate during vigorous exercise; the recommendation was for further validation [36].

In sum, adherence strategies follow a step-by-step process, starting with early patient insights, clinical and economic support during treatment (especially with reimbursement dossiers and copay assistance), and continuous tracking of outcomes and quality of life to support the provider/patient dialogue and self-management.

Structure Options

While an appropriate culture is a primary success factor, different structure options each have trade-offs. A decentralized model embedding patient advocacy within business units ensures the diffusion of this capability into franchises, but it does not break down existing silos. A possible evolution may be the reestablishment of cross-functional teams with deep patient-focused experience and skills.

A growing trend is a centralized structure around a Chief Patient Officer. This high-level global appointment helps communicate the corporate mission and vision throughout the company and across regions. It benefits from a clear role as a center of expertise.

At Sanofi, the objective to ensure that patient centricity becomes part of the culture is supported by a three-pillar framework:

• The first pillar is input and understanding, listening to patients through individual and collective channels and designing solutions based on their needs.
• The second pillar is outcomes and solutions, taking those insights and incorporating them into products and “beyond the pill” solutions. This entails a needs-based patient segmentation. Patients' needs vary greatly from first diagnosis to treatment maintenance ten years later. For communications, some patients prefer direct engagement with a nurse, while others are comfortable with apps and digital coaching.
• The third pillar is culture and community, engaging with online groups and ensuring that every employee has a true understanding of how his or her work can impact patients and improve their outcomes [40].

In conclusion, patient centricity is driven by a transformative culture and involves new models and processes at each stage of the value chain, as well as a comprehensive cross-functional and cross-regional coordination.