Geriatric Opportunities in Pharmaceutical Product Development: What’s New? What’s changed? What’s needed?

This article focuses on three critical considerations in the planning and development of drugs targeted at the geriatric population that present enormous opportunities for the forward thinking life sciences companies. We highlight two current products Pradaxa and Xarelto and discuss the geriatric impact on them as examples of challenges the life sciences industries confront.   In the last website posting, we looked at three of the recommendations that addressed the critical need for the industry and key stakeholders to change the way we all do business to prepare for the upcoming elderly population explosion.  The basis for both articles is a retrospective analysis of the 1990 Institute of Medicine paper “Drug Development for the Geriatric Population.” We plan to conclude the series with some specific recommendations for leveraging the geriatric opportunity.

Three recommendations from “Drug Development for the Geriatric Population” are analyzed below with an eye to the future.

1.    Consider cost-containment policies.  This in fact suggested a re-consideration of cost-containment policies related to medication coverage in the elderly.  The grounds for this recommendation were based on that in certain situations failure to use a certain medication may result in severe consequences for which the treatment may outweigh the cost of the actual medication. This involves a careful cost-benefit analysis to show that not using a certain medication will in fact raise the cost of treatment. 

At the time this document was written, Medicare did not cover outpatient medications. While the majority of seniors held additional Medi-Gap policies, these did not include prescription benefits. In 2006, enacted as part of the Medicare Modernization Act of 2003, older individuals were now eligible for formal Medicare prescription plans (Medicare Part D) either through Medicare Prescription Drug Plans (PDP) or Advantage plans. 

At the same time these plans offer the geriatric population greater access to medications overall, they are still somewhat restrictive.  Given the latest news regarding the elevated stroke risk in older women with atrial fibrillation (AF) regardless of anticoagulation status, we looked at the availability within these plans, of newer agents approved for stroke prevention in AF, specifically Pradaxa and Xarelto.  In clinical trials in which the median age was 71, Pradaxa demonstrated an advantage over warfarin while Xarelto was comparable.  Both agents obviate the frequent monitoring and dietary restrictions required for warfarin therapy.   We evaluated formularies for Medicare prescription drug benefits offered by two of the top health insurers in the U.S (one was a PDP and the other an Advantage plan) to determine coverage of these agents.  The Advantage program did not cover either drug.  Although the PDP offers both drugs, they are Tier 3 with an associated co-pay of $35-$45 and necessitate prior authorization.  In comparison, warfarin is Tier 2 with the co-pay ranging from $8 to $12 with no prior authorization required.

The issue of prior authorization for Medicare plans has been increasing.  Based on results of the Avalere Health Analysis in 2011, the percent of drugs requiring prior authorization has increased from 12.8% in 2008 to 16.7% in 2011. 

2.    Quality of life endpoints.  This would expand endpoints beyond efficacy and safety to evaluate those such as measures of cognition and function.  For example, if the drug results in delirium or incontinence.

Review of the literature, commentary, etc. has revealed that there is still a call to action for such endpoints.  To confirm this, using the website clinicaltrials.gov we performed a search of all interventional trials involving patients >66 years of age in which “cognition” was included as an outcome measure.  Out of 209 trials, only five did not evaluating therapies for diseases involving the brain such as Alzheimer’s and Parkinson’s disease.  Although there is significant interest in including such endpoints for drugs used in older individuals, the level of importance has not been recognized by industry.

Efforts are being made by regulators to encourage the inclusion of such geriatric-specific endpoints.  In the U.S. and in Europe, regulatory bodies have stated the goal of ensuring that drugs used primarily in the older population have been in clinical trials which adequately represent these patients.  The document titled Guidance for Industry:  E7 Studies in Support of Special Populations: Geriatrics states that “certain specific adverse events and age-related efficacy endpoints should be actively sought in the geriatric population, e.g., effects on cognitive function, balance and falls, urinary incontinence or retention, weight loss, and sarcopenia.” 

3.    Discontinue use of unsafe or unneeded drugs.   This involved a review of the drugs being used in older patients and how they are used.  Based upon this assessment, if a particular product is not demonstrating benefit in this patient population or places them at an increased risk for an adverse drug reaction, a suitable alternative should be identified.  

Not long after this recommendation was made, the Dr. Mark Beers in collaboration with other experts released the Beers Criteria for Potentially InappropriateMedication Use in Older Adults, informally known as Beer's Criteria.  The criteria is a reference for healthcare professionals as it outlines drugs for which the risks outweigh the benefits in those 65 years and older.  With a handful of revisions since its inception, the Beers Criteria remains the foremost guide to drugs which either pose high risks of adverse effects or seem to have limited effectiveness in the geriatric population.   Currently it categorizes drugs in the following ways: (1) potentially inappropriate for older people because they either pose high risks of adverse effects or appear to have limited effectiveness in older patients (2) potentially inappropriate for older people who have certain diseases or disorders because these drugs may exacerbate the specified health problems (3) used with caution in older adults.

In the meantime, other tools have been developed including the Screening Tool of OlderPersons’ (STOPP) criteria.  Furthermore various mechanisms to reduce the prescribing of potentially inappropriate drugs (PIMs) in the elderly have been put in place at the regional and local levels.  Regardless of available to tools and initiatives, considerable use of PIMs persists.  A study from a group at Weill Cornell Medical College identified 38% of U.S-based older adult patients receiving home care were prescribed at least one PIM.  A similar prevalence was found in Australia in which almonst 50% of a sample of community-dwelling older adults was found to use at least one PIM.   Lack of awareness among the general community of healthcare professionals may be one major reason for this relatively high rate of PIM use.  A survey  of eighty-nine physicians revealed that despite the fact that an estimated 25% of their practice consisted of patients > 65, many exhibited a poor knowledge of PIMs and were unaware of prescribing guidelines such as the Beers criteria.  

There is still much to be accomplished with respect to pharmaceutical management of older adults in order to address this great demographic shift.  Nonetheless,  this offers a wide open opportunity for industry to demonstrate innovation and product differentiation.  The next post will provide a framework for what the industry could be doing to leverage this potential by means of product development efforts.   In the meantime, I look forward to your thoughts on this analysis.