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While many pharmaceutical companies are focused on maintaining prescription refills as part of a sales effort, there are those in development who also are concerned about the impact on safety and efficacy data from clinical studies. If a clear picture of compliance is not available during development, there will be errors in trial precision, time to result, and the decision to continue or halt a program.

More disease areas are starting to examine what non-compliance means in their development paths. At a recent meeting of NCDEU, (a well known, NIMH sponsored gathering of mental health professionals involved in all kinds of psychiatric trials) several talks acknowledged that the non-compliance rates typical in trials for depression patients can range upwards of 40%. Trials in depression are also challenged by a high placebo rate (average 40% but up to 50% not uncommon) that already makes it difficult to separate drug effect from placebo (over 50% of clinical trials in depression fail to separate active drug from placebo). An underlying misunderstanding of compliance in a trial could substantially alter the picture of efficacy that is created and, therefore, the overall outcome. Conference proceedings are available at the NIMH website under NCDEU, 2008 abstracts.

A second important event marking the advance of adherence as an issue in development, was the first-ever conference focused entirely on adherence issues from a development and regulatory perspective. Entitled Improving Drug Development Using Patient Adherence Data in Clinical Trials, the conference was sponsored by DIA and included such notable speakers as Carl Peck, former director of CDER, Allisdair Breckenridge, head of the UK MHRA, and development experts in HIV, transplant, and cardiovascular medicine across research organizations and pharmaceutical companies. Conference proceedings are available at www.dia.org. A theme across many presentations was the challenge of measuring adherence accurately and the impact it can have on efficiency and effectiveness in any clinical trial stage.

Over the next year, Xhale, Inc., a company developing breath-based adherence monitoring systems as well as breath-based diagnostics and drugs, will present data from several clinical studies. The Xhale technology platform is called SMART -- Self Monitoring and Reportable Therapeutics -- and consists of a tagged drug and a monitoring device designed for home use for patients to provide a breath sample after every dose. The monitor provides patient reminders for taking the dose and providing a breath sample, and transmits an electronic record of dose ingestion to the trial coordinator, physician, or caregiver.

Virtually any drug can become breath-detectable by adding SMART GRAS taggants to capsules or to tablet coatings. The inclusion of the SMART GRAS taggant into the wall of a capsule or coating on a tablet should not alter the pharmacokinetic or pharmacodynamic properties of the drug and should invoke minimal regulatory burden, as SMART GRAS taggants are compounds already FDA approved for use as food components.

When used in clinical development, a SMART trial provides a completely novel type of definitive adherence data by documenting the ingestion of medication and time of dose. This definitive adherence data will enable the analysis of the clinical trial data in new ways; i.e. efficacy and safety data could be stratified by level of adherence, and trials with small effect sizes could be reanalyzed to determine if the effect was greater in the high-complier population, providing valuable information on the drug program. In product applications, a SMART drug version could assist the caregiver in oversight of adherence and provide a better indication of whether the patient is actually taking their medication than prescription refill data. In many cases, insurers, physicians or caregivers could implement incentive systems that directly incent the action most important to therapeutic benefit - taking the drug. In some settings, patients would opt in to prove they are adherent in order to earn incentives, help their caregiver, or provide proof of compliance to insurers or others involved in monitoring their healthcare.

A key theme at last years eyeforpharma conference was that adherence and compliance have many stakeholders in the organization but have not always received their due in terms of prioritization and investment. Xhales goal is to support and expand efforts to monitor and improve non-compliance across all settings with a tool that provide the next generation in precision and information.

Author: Deebie Symmes, VP Business Development, Xhale