 |
|||
|
GfK HealthCare | May 2011 | |
|
|||
The Art and Science of Telling the Mechanism of Action (MOA) Story  By Donna Kelly, Chief Consulting Officer and Alice Liftin, Senior Vice PresidentProduct development is shifting to niche compounds, biologics and vaccines As opposed to the 20th century, when blockbuster agents were tweaked to produce many similar compounds (e.g., 13 angiotensin receptor blockers), product development in the 21st century will focus on more targeted and specialized agents with the goal of providing more effective treatment for smaller subsets of the population versus the scattershot approach of some of the previous century’s medications. For example:
Data show that the number of people on multiple drugs has steadily increased over the past 10 years, due in large part to the aging populations in western/industrial countries. This leads to greater challenges around keeping track of drug interactions.  Because of the growth of polypharmacy, it becomes a medical as well as a medical-legal challenge for physicians to understand which medications may be used by a given patient and which may not. Understanding the mechanisms of action of multidrug regimens has thus increased in importance for practitioners. Understanding drug MOA will become even more important As market researchers, we often hear rank-and-file physicians tell us that they “don’t care” about how the drug works, just that it does work. They say they have forgotten most of what they learned about biochemistry in medical school and have no interest in the “gory details” of how a drug acts upon the body’s physiological processes. Often, when we ask physicians to “build the most compelling story” for Product X, they will underplay the importance of MOA in that story in the abstract, but unfailingly include it as part of the introduction to the story, as the setup for why the new agent should be used. As a result of this physician ambivalence about MOA, marketers are challenged to leverage a drug’s MOA in a way that makes physicians care about it. While physicians have always needed to have some understanding of drugs’ mechanisms of action, their need to understand MOA as a way to make decisions about treatment will become even more important as totally novel MOAs are introduced and more patients are on multiple-drug regimens. In a poll and threaded discussion conducted by GfK HealthCare and WebMD (Medscape Physician Connect from WebMD, the largest physician-only social network on the Internet), physicians were asked to respond to several questions about new medications’ MOA. The graphic below summarizes their responses to three of the poll questions.  As these results demonstrate, the majority of physicians believe that for new medications, an understanding of the MOA helps them make better clinical decisions. Physicians’ comments on the WebMD threaded discussion explain the value that a good understanding of the MOA provides:
The pharmaceutical industry has emphasized the development of a strong selling story for new medications. Most often, this story focuses on the benefits of the medication and the MOA may be relegated to a reason to believe the product’s benefits. Novel mechanisms are the focus of R&D pipelines so in the future physicians will face even more choices involving new approaches to treatment and will need to understand where new agents fit. Prior to gaining clinical experience with a novel agent, physicians will lean on the MOA to make decisions about when and how to introduce the new agent into treatment regimens. Thus, a story that communicates this idea clearly is needed.  The ideal MOA explanation, similar to the overall drug’s selling story, needs to possess the characteristics summarized in the graphic above. Several of these criteria are interrelated and more conceptually than actually distinct, but describing them separately may help us understand the multidimensionality of successful MOA messaging. Clinically Meaningful MOA Perhaps the most important contributor to the successful use of MOA is to explain how the agent works in a way that is clinically meaningful to practitioners. A drug’s MOA can help connect the dots regarding why the physician should care about how it works. It can also enhance the credibility of a new drug’s superiority claim. Physicians are often reluctant to try a new agent and may be hesitant to accept that a new therapy is as good as reported versus current therapy. A clinically meaningful MOA can lend credence to claims of superiority for a new drug’s use as a reason to believe the promise, based on scientific, rational MOA grounds. The very 21st century notion of targeted therapy is itself an MOA construct and inferentially conveys to the physician two things: that the therapy has a narrower side effect profile and is therefore less toxic to the patient; and/or that it has more missile-like (and therefore potent) efficacy. Practice-Changing MOA – Helps underscore what is unique/novel about the drug Very much related to the “clinically meaningful” requirement of successful MOA deployment is whether it conveys that the drug will be practice-changing, e.g., will require the replacement of or addition to current treatments on a routine basis. Inherent in the practice-changing nature of a drug’s MOA is its uniqueness – what unmet need does it address, what new target does it hit? For example, a new cardiovascular agent used its MOA to challenge the market leader. It claimed, importantly, that it was a first-in-class agent – so it was a unique MOA - and was effective in patients regardless of their CYP2C19 (enzyme metabolizing) function, as opposed to the market leader, which acknowledged that poor CYP2C19 metabolizers did in fact exhibit higher CV event rates than those with normal metabolizing function of that enzyme. Potentially, this clinical benefit could challenge the current agent’s position because it helps physicians understand who of their patients will be eligible for this new treatment (versus current therapy), and may also help answer the clinical question of why the market leader works in some patients but not in others – a discomfiting issue for physicians when they prescribe an agent and it fails the patient for unknown reasons. MOA Provides Nonrational/Emotional End Benefit Also related to the clinical meaningfulness of a drug’s MOA is whether it can tie the product’s use to a nonrational/ emotional end benefit for the physician – or the patient. If it can provide a clear emotional benefit, it has gone a long way toward focusing physicians’ interest. For example, a widely used oncology agent conveyed its anti-angiogenic MOA in very broad terms: it helped to cut off the blood supply of cancer cells and thereby reduce the tumor’s ability to replicate. This inferred applicability to a wide range of cancers provided several end benefits to physicians: (1) It made this agent an easier (risk-reducing) choice; (2) it made it easier to explain to patients and caregivers who might need persuading to sign on for a toxic oncology therapy; and (3) it added to oncologists’ sense of confidence that they were making the right treatment decision. These emotional end benefits may all have added to the success of this oncology drug. Developers do need to be careful not to hang their hats entirely on MOA, since its uniqueness may be superseded over time; it may also backfire if the benefit promised by the MOA is not fully borne out in clinical practice. In the case of the oncology agent referred to above, its MOA story became such a powerful support for its broad use in many cancers that when it recently failed to show benefit in a new tumor type, some oncologists began to rethink their use of the agent in general! Parsimonious MOA – Simple and Nontechnical Even in very data-driven therapeutic areas (such as oncology or anti-infectives), rank-and-file practitioners desire an MOA story that expresses how the drug will fit into their treatment regimen. As noted earlier, practicing physicians do not necessarily know/remember the science or the terms associated with a product’s MOA – and don’t like being reminded of their deficiencies in biochemistry. If the MOA can, in simple terms, describe what a product does or how it works, and makes intuitive sense to them, it helps them accept the agent. A good example of how a complex physiological process can be simply explained to physicians and their patients is a new cancer vaccine that is indicated for some types of advanced prostate cancer (PCa) patients. This agent provides a simple and nontechnical story to physicians as to how vaccines work, as well as how their procedure for pheresing a cancer patient’s own blood cells, treating them with the product, and then re-injecting those blood cells into the patient work. On its home page, this new agent is described as “the first in a new class of autologous cellular immunotherapies that use a patient’s own antigen-presenting cells (APCs) to stimulate the body’s immune system against prostate cancer.” This description communicates what the agent does and how it does it, in a concise and clear manner. For patients, this agent’s immunotherapy MOA is explained even more clearly as a story: that it “stimulates a patient’s immune system to target and attack prostate cancer.” (As an aside, the terms “attack” and “target” also resonate with cancer patients and practitioners, who often envision cancer treatment as a “battle”—i.e., it also communicates in a way that emotionally resonates.) Memorable MOA – Tells a Story Graphically or Visually Once the clinically meaningful story can be told in relatively simple, nontechnical terms, it helps to add graphical or visual representations for increased memorability and comprehension. A noteworthy trend among drug reps is to employ visual tools, such as iPads, in physician details to help describe their products in a memorable and graphical way. One recent study conducted by GfK noted that some physicians found animated MOAs on an iPad to be an extremely useful method for explaining relatively complex MOAs. Another approach to making a drug’s MOA – and therefore the product – memorable to physicians is to have its name describe its activity. For example, some cancer agents are described as having a “dual MOA,” which allows the physician to intuitively understand that it can provide a one-two punch to the tumor. In the HIV world, there is a class of drugs that prevents the HIV virus from entering a cell – they are called entry inhibitors and thereby provide a reminder of how and why they work. In head and neck cancer, some agents are described as radiation sensitizers, which reminds practitioners why these agents should be used (it enhances radiation’s benefit) as well as when (in early line therapy) and how (in combination with radiation). Can Be Easily Explained to/Grasped by Patients If your MOA story is simple and nontechnical, as well as visually depicted, it can also be put to good use when physicians need to explain the new drug to patients – for example, when MDs need to persuade patients to accept the new agent. Our research has found that physicians increasingly need to provide a persuasive argument for their treatment decisions to the patient or caregiver, as these stakeholders become more vocal about their own concerns and needs. Moreover, a clear, nontechnical (and when possible, visual) representation of the MOA can be very useful to other health care professionals, such as practice or infusion nurses, who are often called upon to interact with the patient and answer their questions about the drug. In Summary The ideal MOA message is clinically relevant for the physician and helps the practitioner explain the treatment to patients. Those agents that seem to have crafted a successful MOA story have in common the following characteristics:
[The authors would like acknowledge GfK HealthCare colleagues’ contribution to this article’s ideas and examples, including: Tom Alesi, Associate Vice President, Victoria Chen, Senior Vice President, Mimi Doi, Associate Vice President, John Fracek, Vice President, Will Leskin, Senior Vice President and Neil Wasserstein, Vice President] |
Want to learn more on this topic? Please contact:   |