Why oncology companies should care about drug adherence

Conventional wisdom in pharma holds that cancer patients are highly adherent to oral medications, but that may not be the case - and this has significant implications for drug developers.  At ASCO this year, a session featuring Dawn Hershman (Columbia), Soko Setoguchi-Iwata (Duke) and Winson Cheung (British Columbia Cancer Agency) highlighted some facts that I found surprising:

  • Oral medication adherence in chronic diseases is only ~50% in the developed world
  • Even in cancer, maximum adherence is often only ~80%, and it can be much lower for therapies taken over longer periods (see here, here and here for examples in breast cancer, and here for data in CML)
  • Low adherence to cancer drugs can be linked to a significant increase in all-cause mortality (see here and here for examples in breast cancer)

Why should oncology companies care about drug adherence?  First, and quite simply, revenues - and specifically, low-risk revenues.  After all, a dollar spent on increasing adherence for a drug that's already on the market is statistically more likely to yield returns than one spent on, say, R&D.  (More on how to invest that dollar in a moment.)

In addition, low adherence will cause reduced real-world anti-tumor efficacy compared with what's seen in clinical trials, where adherence is tightly monitored and controlled.  Improving adherence could lead to better outcomes (see above), and also prevent physicians from getting an incorrectly poor impression of a drug's utility.

Adherence also provides pharma companies with an opportunity to forge better relationships with payers, who are increasingly focused on this issue.  (If you're going to pay for a drug, wouldn't you want it to have the best chance of doing what it's supposed to do?)  From payers' perspective, maintaining adherence will be particularly critical if they either encourage or force manufacturers to develop value-based pricing schemes that link price to outcomes on a per-patient basis (as I believe is likely, per prior arguments).

Finally, helping to increase adherence would address a problem in the eyes of oncologists - and this would make pharma companies enablers of improved patient care, not merely providers of medications.  This more holistic view of the role of drug developers could help establish a more productive relationship between manufacturers and providers, rather than one that can border on antagonistic.

The bad news for cancer drug developers is that there's no "one-size-fits-all" solution to low adherence.  Per Dr. Cheung's summary at ASCO, patient factors (lack of understanding, sociodemographics, polypharmacy), treatment factors (adverse events, regimen complexity, cost, duration), system factors (inadequate family or pharmacy support, low access, poor outreach) and clinician factors (miscommunication, lack of follow-up, insufficient resources) can all contribute, but their relative importance likely varies depending on the drug, tumor type and patient population - and in any event, adherence in oncology is relatively under-studied.  Thus, it's not obvious for any given development-stage program whether to focus on, for example, text messaging solutions to remind patients to take their meds, or coupons to help ensure patients can afford to fill their prescriptions in a timely manner.

But even in light of this uncertainty, I think there are three things cancer-focused pharma companies should do in this area:

  1. Devote resources to studying cancer drug adherence, perhaps via "open innovation".  There's clearly a huge need and opportunity to better understand the root causes of low adherence in oncology and their relative importance.  As a minimum, companies should ensure they understand the barriers to adherence for their own marketed oncology drugs.  But I'd argue further that much greater insights can be gained by looking across drug classes and indications - and that effort may be perfect for a precompetitive collaboration, where the larger amount of information to be gained by collaborating would not have "proprietary" value, but would significantly enable companies' individual efforts.
  2. Spread bets across many types of solutions.  The landscape of potential approaches to improve adherence is extremely fragmented, particularly in the digital / technology space (see here and here, for example).  But the good news for oncology companies is that compared with developing anti-cancer drugs, accessing and implementing many of these solutions is a relative bargain.  Rather than waiting for winners to declare themselves, pharma companies can play a more active role in picking them, and perhaps even helping to guide their evolution and improvement in the real-world.  This may be particularly important in oncology, because many solution providers are focused on common primary care diseases like hypertension and hyperlipidemia, and it may take some engagement and education for these companies to appreciate the need and opportunity in relatively smaller cancer indications - much like the dialogue that has taken place in oncology molecular diagnostics with test developers.
  3. Collaborate on improving adherence across the healthcare system.  Payers, community physicians, oncology-focused healthcare networks and patients all have important perspectives and insights related to cancer drug adherence.  No one segment (and especially not pharma) has enough in-house expertise or capabilities to improve adherence alone without actively engaging all the other stakeholder groups.

A recent article by oncologist Ethan Basch argued that cancer drug developers need to pay more attention to the "patient experience".  Adherence is a particularly critical manifestation of that experience, and addressing it not only makes good clinical and moral sense for pharma companies, but also  good business sense.