3 Drug Industry Challenges in Targeting Patient Value

Drug companies are getting better at targeting patient value.

In 2010, a drug company was working on new ways to differentiate their cancer drug (Drug 2) from the market leader (Drug 1).

Both drugs had similar efficacy and similar incidence of adverse events (AEs).

However, the AE profile for Drug 2 was a bit different from Drug 1. Based on this fact, Drug 2 researchers hypothesized patients would prefer the experience of being treated with Drug 2 over Drug 1.

As such, the company invested in  a multi-million dollar randomized controlled “patient preference” study – something never done before.

In the study, patients received each drug for a period of 10 weeks with a 2 week wash-out period in between. Once 22 weeks had passed, patients were asked which course of treatment they preferred.

The results were astounding – 70% vs 22% preferred treatment with the Drug 2. The greater preference for Drug 2 resulted despite the fact that 97% of these patients experienced AEs (99% did on Drug 1).

The implications for this study go way beyond a single trial and two cancer drugs.

You see, this study highlighted the potential for demonstrating value of a drug in terms of the patient experience while on treatment. Even more, the study showed that a similar drug in terms of traditional efficacy and safety endpoints could be highly differentiated in terms of patient value.

This kind of value can only be demonstrated by understanding the experience of the patient while on treatment.

Thus, there is a need to gather patient perspectives about their experience of treatment… a need for targeting patient value.

Accelerating the need is the recent launch of multiple “value frameworks” by provider and policy groups. These frameworks attempt to quantify clinical and economic aspects of drugs and translate them into value scores across different domains. Currently, they fall short of including direct measures of patient value but have stated intentions to do so (read more HERE).

But targeting patient value is challenging for drug companies.

This article will help you understand some of these challenges in targeting patient value. Identifying them is the first step in overcoming them.

Major challenges include:

1. Defining & Quantifying Patient Value
2. Anticipating the Evolving Regulatory Landscape
3. Predicting Value Framework “Winners”

Challenge #1: Defining & Quantifying Patient Value

One of the first major challenges for industry is how to better define and quantify patient value.

Actually, work has been done in defining and quantifying patient value for decades. This work is well-known in the scientific field of health economics & outcomes research (HEOR) but is little-known elsewhere.

Regardless, there is a great deal of activity in defining and quantifying patient value. Something is still missing. In order to understand this dynamic, we’ll look at traditional and evolving assessments of patient value.

Traditional Assessment of Patient Value

Let’s start by looking at how patient value has been traditionally assessed.

Health-Related Quality of Life (HRQoL)

In health economics, we talk about patient value in terms of health-related quality of life (HRQoL).

Health-related quality of life (HRQoL) is a multi-dimensional concept that includes domains related to physical, mental, emotional, and social functioning. It goes beyond direct measures of population health, life expectancy, and causes of death, and focuses on the impact health status has on quality of life.¹ Health-Related Quality of Life and Well-Being. Available at: https://www.healthypeople.gov/2020/about/foundation-health-measures/Health-Related-Quality-of-Life-and-Well-Being. Accessed May 2016

But how do we quantify HRQoL?

Economics and health economics use metrics of “utilities” to reflect the preferences of individuals. Utilities are a measure of usefulness of any given good or service.

Health economists have settled on a common denominator for health utilities called the Quality-Adjusted Life Year or QALY for short.

The quality-adjusted life year (QALY) is a generic measure of disease burden, including both the quality and the quantity of life lived. It is used in economic evaluation to assess the value for money of medical interventions.² Quality-Adjusted Life Year. Available at: https://en.wikipedia.org/wiki/Quality-adjusted_life_year. Accessed May 2016

The definition of QALY may sound complicated.

But the QALY is nothing more than 1 year of life adjusted for the quality of that life.

For example, if I am completely healthy for an entire year, I earn 1.0 QALYs over that year. In contrast, if I get injured and am only 50% of full health, I earn 0.5 QALYs over that same 1 year.

A handful of tools have been developed for measuring and quantifying QALYs.

The EuroQol (EQ-5D) and the Health Utility Index (HUI) are two such instruments that generate QALY data. These tools take the responses from patients to multiple questions and convert them into a summary figures that quantify their quality of life per year (i.e., QALY).

Patient-Reported Outcomes (PROs)

In addition to generating QALY data directly, there are hundreds of instruments that have been developed to measure patient-reported outcomes (PROs).

A patient–reported outcome or PRO is a method or questionnaire used in a clinical trial or a clinical setting, where the responses are collected directly from the patient.³ Patient-reported outcome. Available at: https://en.wikipedia.org/wiki/Patient-reported_outcome. Accessed May 2016

These instruments can be broadly classified as those that are general and those that are disease-specific.

As you would expect, the general instruments can be used to assess PROs regardless of the disease of study. The same instrument can be used to assess how patients feel or function if they have asthma, diabetes, cancer, or any other disease.

In contrast, disease-specific instruments have been developed to assess PROs for one specific disease. The Diabetes Health Profile is used in diabetes. The Asthma Quality of Life Questionnaire (AQLQ) is used in asthma. The Functional Assessment of Cancer Therapy General (FACT G) is used in cancer.

There are hundreds of PRO instruments that have been developed by researchers over the past few decades (over 1,200 by my last search).

Generally, each of them goes through a robust development process that establishes its validity (accurate results) and reliability (reproducible and consistent results over time).

Emerging Assessment of Patient Value

There are several reasons for the emergence of new ways of defining and quantifying patient value.

The QALY uses inputs from patient responses to derive its numeric value. But the output (i.e., the QALY) means very little to the patient. It just isn’t very tangible or meaningful to people.

To illustrate, let’s assume I fill out the EQ-5D and my QALY is 0.8. This can be interpreted in several different ways. It could mean I lived 1 year at 80% capacity. It could also mean I only lived 80% of 1 year. Furthermore, my 20% loss in utility could be interpreted as 20% more sleep, 20% less walking and running, or 20% more days in the hospital.

Now let’s consider the hundreds of instruments available to assess PROs. They certainly give part of the health picture from the patient’s perspective. But researchers are now looking to be more direct when targeting patient value. They are also trying to accommodate the fact the patients’ preferences change over time.

Researchers are now targeting patient value concepts like the following in PRO instruments:

• Value of minimal disruption to normal life
• Value of maintaining emotional well-being
• Value of maintaining activities of daily living (ADLs)
• Value of not being reminded about their disease
• Value of progression-free survival (PFS) in cancer (i.e., knowing the cancer is not growing in the body)
• Value of timely and convenient care
• Value of living to meaningful landmarks (e.g., son’s college graduation, daughter’s marriage)
• Value of being informed about treatment options and knowing additional options remain
• Value of knowing treating doctors are up-to-date about their specific disease and all current treatment options
• Value of being involved in treatment decisions
• Value of care coordination

To illustrate, let’s consider the PRO-CTCAE instrument.

The Common Terminology Criteria for Adverse Events (CTCAE) is a standardized way for researchers to classify the occurrence and seriousness of AEs. The PRO-CTCAE is an extension of the CTCAE. It goes beyond the traditional assessment to capture the experience of the patient when AEs occur.

For example, the CTCAE captures the occurrence and severity of fatigue on a scale from 1 (least severe) to 5 (most severe). In contrast, the PRO-CTCAE captures the same information (i.e., “severe fatigue”) PLUS the fact that the severe fatigue “interfered with usual or daily activities quite a bit.” The PRO-CTCAE goes beyond the occurrence and severity of fatigue to also capture the patient’s experience with that fatigue.

Challenge #2: Anticipating the Evolving Regulatory Environment

The second major challenge for industry in targeting patient value is anticipating the evolving regulatory environment.

In 2009, the Food and Drug Administration (FDA) published a white paper to provide guidance to industry on incorporating PRO research in the clinical development process.[4. HHS. Guidance for Industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. Available at: http://www.fda.gov/downloads/Drugs/…/Guidances/UCM193282.pdf. Accessed May 2016] The European Medicines Association (EMA) provides similar guidance in the form of a publication from 2006.[5. Reflection paper on the regulatory guidance for the use of health-related quality of life (HRQL) measures in the evaluation of medicinal products. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003637.pdf – Accessed May 2016]

The guidance is designed to help drug companies understand the steps involved in pursuing a PRO claim in their label. On the surface, a label claim simply means their PRO data will be published in their prescribing information (i.e., “PI”). In reality, the “claim” designation is incredibly meaningful. The ability to promote the PRO data to healthcare providers and executives and use it to differentiate the drug is greatly enhanced with a label claim.

In reviewing the guidance, however, it is clear the level of investment is significant. The guidance describes labor-intensive processes for developing new instruments with valid and reliable measures. Such a process takes many months or years. As such, the decision to attempt a label PRO claim can delay the start of registrational clinical trial programs needed to establish core drug efficacy and safety. That’s a tough sell in any drug company that is looking to maximize the life on its patent clock which is already ticking.

In addition to the FDA and EMA guidance documents, other publications highlight just how quickly the regulatory environment is changing.

In 2015, the Office of Hematology and Oncology Products (OHOP) division of FDA published a request for PRO data in the following 3 areas:[6. Kluetz PG, Slagle A, Papadopoulos E, et al: Focusing on core patient-reported outcomes in cancer clinical trials: Symptomatic adverse events, physical function, and disease-related symptoms. Clin Cancer Res. 2016;22:1553-1558]

1. Disease-related symptoms
2. Treatment-related symptoms
3. Physical function

The publication specifically highlighted the PRO-CTCAE instrument for meeting assessments #1 and #2 and the PROMIS tool for #3. Despite the unofficial recommendations, there is no mention that use of these instruments would guarantee a PRO claim.

As such, drug development teams need to decide whether they will use an existing instrument, modify an existing instrument, or develop a new instrument based on the patient value targets they choose.

Once this decision is made, the instrument(s) chosen or developed must be integrated into early development trials.

But integrating instruments for targeting patient value endpoints into early clinical trials is non-traditional. Quite simply, the individuals within drug companies are not used to such a workflow.

Here are some key barriers:

First, let’s consider the expertise of the clinical development team running early drug development programs. These scientists are very good at generating traditional efficacy and safety data required for regulatory approval. In contrast, their experience with HRQoL / PRO data collection or instrument development is limited. If they’ve seen instruments assessing HRQoL or PROs at all, it’s only rarely when the tools have been piggy-backed onto their existing trials. In short, they are an afterthought to the critical efficacy and safety data program.

Second, the experts in HRQoL / PRO data collection and instrument development reside in entirely different functional areas within drug companies. This kind of expertise is generally housed in HEOR groups. The HEOR groups focus heavily on data generation after drug launch.

And that raises a clear contrast.

The clinical development team is focused on early product efficacy and safety data generation while the HEOR team is focused on late product effectiveness, safety, and HRQoL / PRO data. These two groups are used to working in different extremes of the drug product life-cycle.

As such, there is an intentional organizational shift that must occur to connect the HEOR expertise with the early clinical development team. Doing so optimizes the early integration of targeting patient value within the entire drug development process. Drug companies that do this well will have the most robust patient value data to communicate to the market and support a strong differentiation strategy.

Third, the regulatory environment requires efficacy and safety data for regulatory approval. It does not generally require HRQoL / PRO data. As such, the latter are seen as “nice-to-have” and are not necessarily prioritized in drug product development.

Since they are not required, drug companies lean towards not investing in HRQoL / PRO data generation. This is starting to change because of increasing access restrictions. But for now, only drug companies who have the foresight to leverage greater opportunities to differentiate in terms of patient value are routinely investing in this kind of data generation.

Challenge #3: Predicting Value Framework “Winners”

The third major challenge for industry in targeting patient value is predicting the value framework “winners.”

Any company that invests in generating patient value data wants that investment to pay off in terms of good positioning within emerging value frameworks.

But there are several barriers to predicting how good the patient value data will be reflected by these tools.

First, the same drug can look drastically different depending on which value framework is used. The variable value domains used and scoring systems employed by each framework create different ratings of value across frameworks.

Second, the value frameworks are in their relative infancy. As such, we expect them to morph over time. However, it is unclear how often or by how much they will change. Thus, efforts to target patient value endpoints that score well today is no guarantee they will score well in 2 to 3 years when the frameworks are likely to have changed.

Third, not every stakeholder will use every value framework to assess product value for their business. The frameworks can be broadly classified in 1) those that are useful for doctors at the individual patient level, and 2) those that are useful for healthcare decision-makers at the population health level (read more HERE). As such, targeting patient value endpoints that score well across multiple frameworks is difficult.

Fourth, there is no guarantee that the frameworks available today will exist in 2 to 3 years once our data is mature. Furthermore, new frameworks may emerge that are comprised of completely different value formulas.

Wrap-Up: 3 Drug Industry Challenges in Targeting Patient Value

The drug industry is facing many challenges in targeting patient value. As discussed above, a few of them include:

1. Defining & Quantifying Patient Value
2. Anticipating the Evolving Regulatory Landscape
3. Predicting Value Framework “Winners”

Evolving methods of defining and quantifying patient value are starting to complement traditional methods like HRQoL and PRO assessments. They are looking to capture the patient experience of treatment – how the drug’s efficacy and safety affect their experience of life.

At the same time, the regulatory landscape around patient value endpoints has been evolving to offer guidance on PRO claims. Such claims have great benefits for drug companies in terms of promoting product differentiation.

However, the investments in pursuing PRO claims and the lack of expertise in traditional clinical development teams has hindered their widespread use. Drug companies have to be intentional about merging the PRO expertise from internal HEOR teams with the early clinical development teams.

Ultimately, the way patient value is scored per emerging value frameworks is a moving target that is difficult to anticipate. In the meantime, drug companies may have to focus their patient value development plans for different reasons – namely, because it is the right thing to do for the patient.