When mountain climbers venture into difficult terrain, they can rely on topographic maps and GPS devices. Matters aren’t so simple in the pharmaceutical business. Drug developers face a landscape that is continually reshaped by new technology, regulatory changes, shifts in prescribing patterns, innovations in care delivery, and changing payment models.
Even results from clinical trials published in peer-reviewed journals may not be able to deliver the certainty or predictive power of how the treatment will perform in real life. While trial data may point toward likely medical outcomes, in the real world patients suffer from comorbidities, subpopulations respond to drugs in different ways, and there can be many other surprises.
Now, a methodology known as evidence mapping is helping drug developers grapple with market uncertainty. Designed as an interactive data grid, this analytic technique gives users an early read on how regulators, payers, patients, and providers are likely to review and respond to new pharmaceutical products as well as how the horizon may change perspective and requirements.
Even after a drug reaches the market, pharmaceutical companies can update the map as circumstances evolve. This helps demonstrate to stakeholders on an ongoing basis that the product is not only safe and effective when compared with other medicines, but also worth the price. Increasingly, health insurers, employers, and governments that offer plans or health insurance coverage are demanding to see such evidence.
In a recent survey of 100 U.S. health insurers and pharmacy benefit managers by PriceWaterhouseCoopers’ Health Research Institute, 82% of respondents said that drug manufacturers must demonstrate clear clinical benefits of their products, compared with existing generic and branded treatments. Some 78% said the drugs must also save money. An evidence map helps the company assemble the different pieces of information needed to make the case.
Drafting an evidence map
To be effective, this methodology must meet three goals. It must define the options to demonstrate value and criteria for a successful drug in a particular disease market; show what’s required to meet those criteria; and establish priority for investment to deliver, on a market value threshold, one or more development assets or programs over various competing projects.
For designers of an evidence map, the first step is to track down all the important information on drugs —either on the market or in the pipeline—that address a particular condition. In addition to the list of direct and indirect comparators, the map also captures current and future key attributes that identify the clinical and economic impact of managing the disease. The attributes are a set of comparable characteristics and performance value thresholds of competing therapies, based on a spectrum of clinical and patient-reported outcomes, which vary depending upon the disease category.
To make sure these attributes are relevant, the development team may enlist a panel of experts ranging from clinicians, academic authorities, and members of patient advocacy groups to insurance executives, staff at health technology assessment (HTA) organizations, and advisors to the U.S. Food and Drug Administration and to its counterparts overseas. These panelists will help review regulatory developments, reimbursement trends, differences among patient subpopulations, and other elements. Each relevant detail and insight will eventually be added to the grid.
The universe of data resources is vast. Much of the information comes from news and articles in peer-reviewed publications. But evidence mappers may also draw on coverage in the financial press, analyst reports, blog posts by scientists, medical conferences, message boards of support groups, and social sites such as PatientsLikeMe. Indeed, social media may be in the vanguard; for example, when it comes to tracking adverse events among patient subgroups. More formal patient-reported outcomes (PROs) also provide an essential piece of the picture, as do real-world data such as drug prescription claims.
Finally, the map incorporates both linear and weighted rating scales that help gauge the importance of key attributes and predict the performance of therapy/drug comparators. These opinion-driven assessments are based, in part, on input from the panelists and experts mentioned above, and will reflect both value and value thresholds that may be required to gain the ability to differentiate a product in a real-world setting.
Utilizing the grid
Built in Microsoft Excel to assure ease-of-use, the grid consolidates concrete results from patient reported, clinical, observational and economic trials, which are assigned numeric scores, as well as assessments from reviewers. Comments, supporting data and links to web sites are also embedded. One virtue of this format, compared to a linear report or flat table, is that it allows users to step back and scan the results in a bird’s-eye view. Coded by color, this snapshot lets the user locate areas of interest and potential differentiation, without being distracted by the data.
One color, for instance, may alert the viewer to disease pathologies that aren’t currently addressed by any medication. Another color could signal the opposite: areas where the company faces a high risk of failure or low potential rewards, either because the market is small, the niche is well-served, or payers are skeptical. By clicking on the color region, the user can drill down in the data or tab over to related comments and web links.
The ability to embed expert assessments is critical when looking at development programs that promise improvements only at the margin. In diabetes care, for example, many new treatments may offer 0.2% or 0.3% improvement on a hemoglobin A1c test. This is roughly what one expects whenever the patient switches to a new medication. The designers may choose not to flag a given intervention as an area of interest unless the value threshold is 0.5% or greater. By drilling down, the user learns what the number may signify to the typical provider, to a patient subgroup, or to insurers who have said they will pay more for an improvement in this range.
Having all the data within easy reach facilitates so-called value threshold analysis. This brings significant benefit when tackling a condition such as psoriasis. An evidence map lets the drug developer select a specific outcome and immediately see what it looks like from the vantage of the patient, the payer, or any other stakeholder.
With psoriasis, for example, doctors are accustomed to judging drug effectiveness based on partial remissions, calibrated in terms of surface area affected and, perhaps, graded with an “itch score.” Total patient satisfaction may also be swayed by adverse drug interactions, frequency of dosing, price, and other factors. With the aid of a map, the drug developer is able to segment the value of an experimental or approved drug by health-care constituent, by patient population, and by total cost. The company can spot the best opportunity to differentiate the product and see exactly what is needed for the payer to see the value in the treatment.
Risks and rewards
Building an evidence map requires painstaking research on the front end. New technology isn’t predictable—exemplified by the high number of failures in Phase 3 clinical trials. For the map to be useful, researchers may have to take stock of every relevant citation on PubMed, every related entry in ClinicalTrials.gov, and all recent news reports. Even with these efforts, they still can’t know how ongoing double-blinded trials will turn out. Without that information, there’s a degree of haze on the horizon.
Yet, the benefits of gleaning knowledge far outweigh the risks of missing something that can’t be known. This is why the data-gathering part of the exercise requires such a wide aperture. For example, a drug company whose focus is on the U.S. market may not recognize the importance of regulatory trends in Europe until the information is spotlighted in the evidence map.
The fact is, trends outside the United States can have an impact in all markets. The European Medicines Agency (EMA) is currently coordinating activities with HTA agencies in several member countries, part of a concerted effort to thrash out unified responses when new drug technologies emerge from the lab. Regulatory coordination with HTA groups is a growing trend in the United States as well.
In the same way, an evidence map can lead the drug developer to fresh insights on a disease of interest. Consider the broad social ramifications of Alzheimer’s disease. There are approximately 5.4 million patients with this condition in the United States, but nearly three times that number fall into the category of caregivers, according to the Alzheimer’s Association—people providing unpaid support for a sick relative. In the context of an evidence map, Alzheimer’s looks like no other illness, in the sense that it is close kin, not the patients themselves, who become the most forceful voice in PRO-related inputs on the grid.
The most powerful lesson evidence mapping provides is that drug developers can no longer function in silos within the organization. In a sense, the evidence map confers the power of a digital avatar. The developer gains the ability to survey the industry and the wider economy, and also scan the horizon with the eyes of a patient, a clinician, a regulator, or a payer.
When any drug company communicates with the FDA or the EMA on matters of drug effectiveness, there are relevant comparisons to other drugs on the market and in the pipeline. But with an evidence map, this panoramic view extends much more broadly. Conversations with the Centers for Medicare and Medicaid Services (CMS) aren’t just about the cost of a drug or managing an episode. They’re about the total cost of managing a disease that the new drug will help to address, and the savings that come with efficiencies in disease management. The map ensures that a new drug is not only approved, but that it’s differentiated from whatever else is out there—or what is expected to emerge—and that the value is identified so doctors will prescribe the medicine, payers will reimburse for it, and patients will benefit.
1. Unleashing Value: The changing payment landscape for the US pharmaceutical industry. PwC Health Research Institute, May 2012: http://www.pwc.se/sv_SE/se/halso-sjukvard/assets/unleashing-value-the-changing-payment-landscape-for-the-us-pharmaceutical-industry.pdf