Addressing the Challenge of Patient NonAddressing the Challenge of Patient Non--ComplianceCompliance

Separating the NonSeparating the Non--Compliers from the NonCompliers from the Non--RespondersResponders

Today’s Topic: Patient Non-Compliance

• Discover the population profiles for non-compliance• Reveal the underlying reasons – symptomatic versus

asymptomatic patients• The implications of non-compliancep p• Strategies for reducing non-compliance risk• What is the value for addressing this issue?• What are the industry obligations we face moving forward?• What are the industry obligations we face moving forward?

What Do We Mean by Non-Compliance?

Non-compliance is the degree to which behavior fails to coincide

with medical recommendations in …taking medication, attending

clinical appointments, following exercise or diet regimens and

engaging in preventative behavior*

*Haynes RB Taylor DW Sackett DL (eds) Compliance in Health CareHaynes RB, Taylor DW, Sackett DL (eds). Compliance in Health Care

There is No Excuse for Ignorance

• “Keep watch also on the fault of patients which makes them lie about t ki f thi ib d”taking of things prescribed” Hippocrates, circa 500 BC

• “Drugs don’t work if people don’t take them” C. Everett Koop, 1985

I i th ll k i f ti t li• Ignoring the well-know issue of patient non-compliance or non-adherence makes no sense, especially when it is simple to turn a liability into an asset

• Estimated annual cost to the US Health Care System of non-compliance with prescribed medication over $175B

• Ernst & Grizzle, JAPharmA, 2001Ernst & Grizzle, JAPharmA, 2001

• 50 percent of patients are non-compliant

• Boddenheimer & Fernandez, Ann Int Med, 2005, ,

Non-Compliance in the Clinical Trial Setting

• Results of non-compliance include: – Loss of subjects to follow up– Loss of patients to side effects

S bj t t ti li i l it i t– Subjects not meeting clinical criteria to continue in the study

– Injection of error variance into the study

– Failure to complete the study with enough participants to produce statistically significant results

– Requirement to increase sample sizes to compensate for error variancep

How do you Ensure Non-Adherence is not Undermining your Data?

• Traditional approaches to addressing non-compliance

– Patient self reports– Medication diaries– Tablet counts– Monitoring plasma levels

Electronic compliance data show that many• Electronic compliance data show that many of these traditional practices are ineffective

• Parking Lot Syndrome• Weekend/Holiday

Why Non-Compliance??

• Lack of symptomsy p

• Side effects

• Unable to understand dosing instructionsg

– Complicated

– Language/Translation issues

• Forgetfulness

– Generally accepted that blister cards provide a better opportunity for adherence

– Calendar packs

• Complicated multiple drug regimens• Complicated multiple drug regimens

Electronic Compliance Monitors

Pros Cons• Smaller sample sizes or• Increased statistical power

– Greater confidence

• Increased cost• Increased complexity

– TimeGreater confidence

• Quicker decision making• Quicker regulatory approval

Time

• User acceptance– What to do with the data

• More accurate dosing information

• Intra trial feedback• Positive ROI

Mandating Electronic Compliance Monitoring

• Will the FDA issue a mandate as theseWill the FDA issue a mandate as these devices become cost effective and reliable?

• Case Study: NIH sponsored a trial

– Regimen of 1x day for one year

– COPD population

– Made the assumption that this type of trial would typically be plagued with non-compliance

Adherence Data Can Increase Statistical Power

• Resulting in positive ROIResulting in positive ROI

• Reliability is no longer an issue

• Stricter compliance requirements may actually St cte co p a ce equ e e ts ay actua yreduce the N for a trial

• Sample training

• Intra-trial feedback

• Adjusting trial data post hoc for non compliance

• Better correlation of drug/Adverse Events

• More accurate dosing information

Sample Scenarios

• Opiate analgesics– Reduce dependence liabilityp y– Reduce medico-legal liability– Increase clinical effectiveness

• PRN medications; migraine medications• PRN medications; migraine medications, sleep medication

• Critical window drugs– Combination therapies, e.g. HIV,

chemotherapies– High toxicity drugs

• Mandated pharmacotherapy, e.g. cyproterone, naltrexone, INH

• Combination therapies, e.g. HIV, chemotherapies

– High toxicity drugs

Special Populations

• Geriatric populationsGeriatric populations• Psychiatric populations• Addicted populations• Third-world populations• Poorly motivated populations

Where non adherence causes no symptoms– Where non-adherence causes no symptoms– Where non-adherence is catastrophic

• Chronic indications where patients must take medication for long periods of time, e.g. diabetes, organ rejection

Technology to Address Non-Compliance

• Current and planned generations ofCurrent and planned generations of electronic compliance monitors fit increasingly seamlessly into the trials process

– High reliability

– Patient friendly – no patient input requiredrequired

– User friendly

– Highly flexible according to fit user requirements

Three Practical Recommendations for Sponsors Today

• When considering electronic compliance, early involvement from the technical team is critical

• Have a strategy for using the data

• Old paradigms no longer apply