Patient non-adherence to medications is remarkably and stubbornly common, costly, and dangerous. Multiple studies have found that at least half of prescriptions in the United States are not taken as prescribed.
“Poor medication adherence in all its manifestations costs the United States upwards of $290 billion per year in unnecessary health care spending, not to mention illnesses and deaths that could be otherwise prevented,” reports the New England Healthcare Institute.
Not surprisingly, the problem has been well known to industry for many years, so one wonders why progress has not been made. Numerous studies have been conducted to understand the etiologies of non-adherence, and many projects have been launched to develop adherence interventions and programs. The results of both have been inconsistent and discouraging overall.
However, there may now be reasons for biopharmaceutical companies both to be more sanguine and more determined about deploying adherence programs. Three rationales are at play:
• advances in science and technology are enabling effective interventions;
• health care reform is creating an environment well-suited for improved adherence; and
• adherence solutions are excellent fits for new pharmaceutical strategies.
The Non-adherence Predicament
Non-adherence is widespread. “Because of the difficulties in measuring compliance, no estimate of compliance or non-compliance can be generalized, but poor compliance is to be expected in 30-50 percent of all patients, irrespective of disease, prognosis or setting,” according to a review of three decades of research on treatment adherence.
Its effects also touch all major stakeholders, including patients, providers, pharmaceutical companies, insurers, pharmacies, and employers. Non-adherence results in poor clinical and financial outcomes, lost industry revenues, lowered quality of life, and lost work productivity.
For example, the Center for Technology and Aging reports that 33 percent-69 percent of medication-related hospital admissions and 23 percent of all nursing home admissions can be attributed to medication non-adherence.
Conversely, high adherence can lower health care costs. A 2011 Health Affairs publication
• congestive heart failure—$7,823 less;
• hypertension—$3,908 less;
• diabetes—$3,756 less; and
• dyslipidemia—$1,258 less.
All stakeholder groups have been involved over the past few decades to one extent or another in programs to improve adherence. The problem, though, has proven fairly intractable. Incremental improvements seem achievable but applicable only to certain populations, and rarely for long periods of time.
Study results regarding both non-adherence causes and the effectiveness of different interventions reveal that the issue is multidimensional, complex, and without easy solutions.
Nailing down the reasons underlying the non-adherent behavior is critical to a successful intervention. Yet, even this seemingly straightforward objective has only recently, with the input of cognitive sciences, been tackled in a way that is starting to show results. What can be concluded from all of these investigations is that causes vary significantly across patients.
The World Health Organization categorized the factors influencing adherence into five groups:
• socioeconomic-related factors; for example, therapy, affordability, or distance from treatment;
• health care team/health system-related factors; for example, communications with and education of the patient;
• condition-related factors—the nature of the illness, and, for example, the patients’ understanding of their condition;
• treatment-related factors; for example, complexity of regimen and side effects of medication; and
• patient-related factors; for example, forgetfulness and psychological issues.
Other reviews have found that the most common reasons for not adhering to medication regimens are affordability, concerns about side effects and other medication issues, and questions about the need for the medication.
More recently, an influx of scientists from, for example, cognitive psychology, behavior economics, and decision science, have provided new insights into non-adherence. What has been revealed is that a patient’s conscious and unconscious mind-set is an important factor in medication adherence, and one key to determining how best to customize an intervention. “The factors influencing adherence can be complex and multifaceted. They may include socio-economic factors, beliefs and perceptions about benefits, risks and consequences, self-efficacy, anxiety, health locus of control, depression, optimism, distrust, openness to persuasion, and social influence,”
Likely because of these complexities, adherence interventions generally have not met with much success, and certainly no single solution has been demonstrated effective across a broad range of patients and settings. In fact, studies’ findings frequently conflict regarding the effectiveness of a particular intervention, such as reminders or patient education. Meta-analyses of adherence intervention studies indicate that only around 50 percent of the studies found any improvement in adherence at all, with an average improvement of only 11 percent.
“[C]urrent interventions to improve adherence lack a clear, uniform approach by which patient compliance can be universally improved,” conclude Justin Gatwood and Steven R. Erickson in a recent editorial.
It is becoming clear that tackling the non-adherence problem has been stymied by three basic challenges:
• because each patient’s non-adherence drivers are different, interventions need to be personalized to some degree;
• because non-adherence issues are typically multiple, interventions need to be multidimensional solutions that address many factors; and
• because adherence interventions need to be implemented in delivery settings and payer programs suited to supporting medication adherence, new reform initiatives are needed.
Thus, making progress will require major changes to implementing intervention solutions.
Insight—Solutions Require Personalization
A reminder system will not improve adherence in patients who are not taking their medication due to side effect concerns. Conversely, a patient education intervention likely will have little effect on a patient who is forgetful or has problems affording the medication. This explains the unimpressive improvement rates found in studies of interventions focused on a single non-adherence factor. Each intervention can only be effective for the single, minority cohort that has that target issue.
Given the very high diversity of etiologies, an effective adherence enhancement approach must be individualized to the patient’s particular challenges or mind-sets. Segmentation and targeting have been demonstrated to be insufficient. The dimensionality of the non-adherence domain means the population is “micro-granular,” and psychological factors are too complex for traditional approaches.
The answer, many have now concluded, is to turn to what is becoming common throughout our Internet-driven, social media society—tailored messaging and services. Just as Amazon and Google have learned commercially, research also has shown that tailoring to an individual’s situation, preferences, etc., makes for more potent marketing. Improving medication adherence can be thought of as “marketing” to the patient to change behavior towards better adherence.
Tailored messaging has been defined as “any combination of strategies and information intended to reach one specific person, based on characteristics that are unique to that person, related to the outcome of interest, and derived from an individual assessment.”
Message tailoring’s “focus on matching messages to the unique beliefs, attitudes, needs, and preferences of individuals makes it fundamentally different from the common mass communication practices of audience segmentation and message targeting, which operate at the group level,” write S.M. Noar and colleagues.
Brian Bertha of McKesson Patient Relationship Solutions, McKesson U.S. Pharmaceutical, has come to the same conclusion: “In essence, successful solutions combine an individual, personalized approach, while maximizing the most appropriate technologies and other data-based, scientific approaches available.”
Insight—Solutions Require Multidimensional Interventions
One finding repeatedly identified in the medication adherence literature is that simple interventions focused on a single non-adherence factor are relatively ineffective except in very short-term settings. To achieve longer-term adherence, interventions that address multiple issues generally perform better than those single component interventions.
Adele Gulfo, U.S. president and general manager for primary care at Pfizer, explains, “We are not going to crack the code to adherence doing one intervention. Most times it’s going to be multifactorial.”
For example, investigators from IMS Health reviewed studies of cardiovascular adherence interventions published between 1972 and 2007 and “found the most effective approaches for improving adherence are multifaceted. Personalised, intensive interventions offered the greatest improvements in adherence, as was found in our earlier study.”
Again, research indicates that patients’ behavior toward medications is complex and influenced by their situation across five diverse dimensions, as defined by WHO—socio-economic, health care team, condition, treatment, and patient. As has been found for other behavior change programs (for example, Weight Watchers), success requires addressing issues in as many areas as feasible and appropriate.
Insight—Effective Adherence Requires New Care Delivery Settings
Our current care delivery and payment systems do not support delivering high touch, personalized, multicomponent adherence programs. Fee-for-service clinicians have limited time to counsel, educate, and engage patients, and are not compensated for these services. Furthermore, our health care system’s lack of coordination and communication across providers and settings is a barrier to delivering an integrated adherence program.
There are economic arguments within the current marketplace for sponsorship of adherence programs by payers, pharmacy benefit managers, employers, pharmacies, and pharmaceutical companies. However, these programs still must work around instead of with the physician, the exception being large managed-care systems like Kaiser.
In essence, a key element in a solution—the primary care provider—currently has barriers erected that are hampering his or her ability to be effective. Until incentives and organizational structures change, it will be difficult to optimally engage patients in long-term adherence solutions.
However, all that may be changing. New health care reforms such as the patient-centered medical home and accountable care organizations offer much more fertile ground for adherence programs, as will be discussed below.
Biopharmas—A New Business Case for Adherence Programs
Biopharmas have invested and launched adherence programs for many years now, with mixed results. With the alluring target of billions in additional revenues, and physicians who already have been convinced, patient adherence has had the veneer of low-hanging fruit. Yet, Robert Nauman, principal, BioPharma Advisors, asserts, “Adherence is still a very small, insignificant issue within the pharma space. If this is a high-profile drug or if the product is a specialty product or biologic, then it might have the budget to pay for these sizable programs. But that’s often not the case.”
An excellent case can now be made, however, that technologic, market, and strategic dynamics are creating a strong new value proposition for biopharma medication adherence programs. Taken together, these factors argue for elevating the importance and role of medication adherence offerings in the biopharma business model over the coming decade.
Scientific and Technologic Advancements in Interventions
As we have all witnessed over the past few years, technologic advances have been explosive in terms of ease of use, ubiquitous access, and intelligence. Commercial software’s ability to mimic human intelligence has become surprisingly good in terms of vocal and written interactions. Combined with the wide range of devices that can be used to channel communications, this functionality enables personalized interventions that fit seamlessly into a patient’s life.
In parallel, scientific insights from cognitive psychology and behavioral economics, which deals with consumer decision making relative to incentives, are driving new, more effective adherence algorithms.
Smarter
For example, HealthHonors Corp., a subsidiary of Healthways, has developed “Patient Reinforcement Plans™” that uses “Dynamic Intermittent Reinforcement™ (DIR™) software,” that is, “sophisticated algorithms that can use historical data (pharmacy claims, medical claims, segmentation data, psychographic data, when available) and/or behavioral data (personal engagement patterns and preferences) to create optimized reinforcement schedules.”
The system is smart enough to learn from patient behavior, automatically tailoring reward points to reinforce adherence behavior. Educational messages are delivered at peak acceptance points and refill needs are predicted and facilitated automatically. An adherence study of patients prescribed statins found, “Adherence increased and remained at high levels with the intervention over the course of the program. Adherence as measured by refill rate improved from 72.7 percent to 97.9 percent, a 34.6 percent relative increase (P = .0016).”
Motivational
Not only do we have an endless stream of new gadgetry from our technology advances, but we have learned a variety of important new insights about consumer behavior from our “living lab” experiences with social media applications. Most importantly, adherence interventions are applying knowledge that has been generated about the power of gaming to influence behavior.
Gaming can influence people in at least three ways—competition for rewards, competition to win against peers, and engagement for fun or winning against the game. Interventions using these approaches have shown remarkable results.
Re-Mission (http://www.re-mission.net/) is a video game for young people with cancer in which “players pilot Roxxi the nanobot through the bodies of teenaged cancer patients to investigate symptoms, destroy cancer cells, eradicate bacteria, stop metastases, and manage treatment side effects.” In a large, multicenter randomized, controlled trial (375 cancer patients aged 13 to 29 years old at 34 clinical sites in the United States, Canada, and Australia), Re-Mission players showed much higher adherence rates—they had blood chemotherapy metabolite levels that were 41 percent higher than controls.
A study of warfarin patients evaluated the combination of a lottery system and a reminder to measure effect on adherence. If patients opened their pill bottles appropriately, they were entered into a daily lottery. Outcomes measured included the number of incorrect warfarin doses and the proportion of International Normalized Ratio (INR) levels out of range. The results were a drop in percent of out-of-range INRs from 35 percent to 12.2 percent during the intervention, and a drop in proportion of incorrect pills from a historic mean of 22 percent to 2.3 percent during the lottery intervention.
What these signal is that effective, smart, high-tech adherence programs are becoming a reality. The fact that these interventions can both engage patients in a manner that might also increase brand loyalty, as well as meaningfully increase brand sales, equates to a strong value proposition.
Market Reforms Are Adherence Enhancers
Regardless of what happens at the federal government level, America’s health care system is committed to transitioning away from fee-for-service and toward value-based purchasing, and away from silos of providers to a coordinated, centralized care delivery system. As part of these reforms, including President Obama’s health system reform legislation and initiatives by private payers, new care delivery models such as the patient-centered medical home (PCMH) and Accountable Care Organizations (ACOs) that greatly facilitate effective adherence interventions are being rolled out. The New England Healthcare Institute writes this about adoption of patient adherence: “The time is also right because the U.S. health care system appears poised to embrace system-changing innovations, such as the increased utilization of health care IT, which will facilitate the introduction of interventions to improve patient medication adherence.”
Three ways, in particular, that these types of reform initiatives will optimize the delivery of adherence interventions are:
• they are greatly increasing the availability of and access to providers and care-teams;
• they are driving the establishment of HIT systems for better communication and coordination; and
• they are tying provider incentives to quality metrics and outcomes.
The PCMH pays primary care providers and care teams to spend time with patients engaging them in their care and supporting their self-management, which certainly would include medication adherence. “The patient-centered medical home (PCMH) is a way of organizing primary care so that patients receive care that is coordinated by a primary care physician (PCP), supported by information technologies for self-care management, delivered by a multi-disciplinary team of allied health professionals and adherent to evidence-based practice guidelines. The goal of the PCMH is to deliver continuous, accessible, high-quality, patient-oriented primary care.”
PCMHs are being widely adopted across health care systems and by private insurers such as Humana, Cigna, BlueCross BlueShield, and UnitedHealthcare. PCMHs likely will continue to spread, as numerous pilots have shown they generate substantial savings in terms of, for example, reduced hospitalizations and emergency room visits
PCMHs will greatly facilitate the sort of highly effective multicomponent, personalized, high-touch adherence programs that work best when delivered by providers that have relationships with the patient, and have the time to support them over the long term.
HIT care coordination systems, which are being implemented as part of both PCMH and ACO initiatives, can further increase adherence by incorporating more providers, including ancillaries and pharmacists, into the program. Evidence indicates that receiving messages from multiple health care professionals reinforces the patient’s engagement and self-efficacy.
Providers are compensated by ACOs and other “value-based” payment programs according to quality performance. This aligns their interests with that of the biopharma, and (hopefully) the patient. Adhering to medication regimens improves outcomes, which can directly effect the physician’s compensation.
Also, since the ACO is compensated based on the health care expenditures of its population, it has a major incentive to avoid readmissions and emergency room visits. Thus, its incentives also are aligned with the biopharma.
Finally, another reform initiative likely to drive adherence interventions is a provision in the Patient Protection and Accountable Care Act, or
These reform initiatives give biopharmas another multi-win opportunity. In this case, again, when delivered in new care delivery settings, adherence programs are more likely to succeed and thus deliver higher sales, but the added dividend is incentive alignment and reputation building with physicians, health care organizations, and policy makers.
Biopharma Strategy Needs Adherence
Many biopharmas undergoing their own transitions to new business models that involve less internal R&D and more downstream value are considering adding offerings that complement their medications, to deliver a “therapeutic solution.” Medication adherence programs should be near the top of that agenda for any strategically important medication, especially one facing generic competition.
First, developing and delivering adherence programs leverages biopharmas’ competitive strengths in clinical trials, reimbursement, and sales and marketing. Secondly, adherence programs facilitate new pricing strategies that focus on effectiveness and value delivery. Third, highly effective adherence programs can provide powerful brand differentiation with providers.
• Leveraging biopharma competitive strengths—collaborating with product developers of adherence interventions, conducting trials to demonstrate effectiveness, packaging the intervention into a program and therapeutic solution, and distributing through multiple channels, all are key strengths of biopharmas that need to be leveraged by the new business models.
• Support new pricing strategies—given the value-based purchasing movement, there may be opportunities for biopharma to introduce programs where bundled solutions are offered with minimal, “guaranteed” effectiveness. This becomes more tenable with the availability of potent patient adherence solutions. Moving to this sort of pricing model in developed countries aligns biopharmas with market reforms, counteracts generics, and may forestall attacks on medication prices.
• Provider brand differentiation—as provider compensation becomes increasingly tied to clinical outcomes, prescribing decisions will focus on patient adherence factors. A brand that is bundled with a more effective adherence program will have a clear advantage with physicians. One survey conducted by the pharmaceutical marketing firm HealthcarePanel.org found that “the addition of a rewards-based medication adherence solution shifted reported prescribing preferences between two competing drugs by over 30 percentage points.” The intervention, the HealthPrize Engagement Engine™, an Internet and mobile-based adherence platform that leverages behavioral economics and gaming dynamics, was considered very valuable in terms of increasing adherence by 86 percent of the physicians.
Conclusions
Patient non-adherence has been a tenaciously difficult problem to solve, and one that drains biopharma revenues, costs lives, results in poor outcomes, and drives up health care costs at a time when our system is nearly bankrupt. Although biopharmas have not ignored adherence programs, they are not currently a top strategic objective.
After many years of trials and meta-analyses, the conclusions that are emerging are that effective adherence requires tailoring and a multidimensional approach. Fortunately, smart software, scientific insights, and new care delivery models can significantly advance patient adherence programs.
Adherence programs are a business biopharmas should embrace strategically. Health care market reforms mean that adherence programs are now a nexus point that aligns biopharma, physician, health care system, patient, and insurer incentives. This, in turn, may mean a boost to sales and marketing, a defense against generics, and a new approach to engendering goodwill and loyalty. Improved medication adherence leads to better outcomes and overall health care savings. This is a strategic initiative biopharma cannot afford to pass up.
Learn more about Bloomberg Law or Log In to keep reading:
See Breaking News in Context
Bloomberg Law provides trusted coverage of current events enhanced with legal analysis.
Already a subscriber?
Log in to keep reading or access research tools and resources.