Using Electronic Compliance Monitoring (ECM) in the drug development process

Ward SmithClinical Packaging Consultantward7@fuse.net513-307-8163

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Overview

• WHAT is electronic compliance monitoring (ECM)?

• WHY would you use EMC?

• WHERE is ECM data useful?

• WHEN should you start planning?

• WHO are ECM solution providers?

WHAT is electronic compliance monitoring (ECM)?

• The use of technology to record patient dosing history, as it occurs.

• Transmit dosing diary history as electronic data. (Non-pharma ECM)

Concept started 33 years ago

• As technology has advanced, size of components has come down as well as cost.

• Brief history of “smart packages” designed to monitor dosing compliance

1976$500 each

($1200 today)6 weeks of data

1986$400 each

1991$250 each

2000$80 each

2005$75 each

•Blister Format

HOW does it work?• Modern technology uses ASIC

chip technology and conductive inks to create circuits embedded inside of conventional wallet card designs.

Data Capturing Options

Multiple wireless methods

Daily24 hour

clock

Sequential dosing days

Chronology of Dosage:Desirable

Example of near perfect compliance

Chronology of Dosage:Reality

Increasing timing variationMulti-day dosing holiday

Why us ECM? .

• The problem: Study subjects have proven to be unreliable.

• Their self reporting is highly inaccurate.

• They fail to report missed doses.

• They fail to complete diaries; often waiting until the next site visit to enter dosing data, trying to recall dose times from memory

Unreliable subjects are well documented.

Not all patients report Non-adherence data

• Returned empty bottles/blisters; even when doses are omitted.

• Study patients want to be perceived as cooperative or helpful to study staff.

• Study patents don’t want to be kicked out of a study for non-compliance.

• Hard to report a missed dose when you forgot to take it. (Can’t report what you don’t remember).

Where is ECM data useful?

• Who is a Non responder vs. non complier?

• Accurate insight into drug “forgiveness”

• More accurate assessment of minimum effective dose

• More accurate assessment of maximum tolerated dose

Case: Kuopio University HospitalOpioid Substitution Treatment

Electronic packaging• Dose control and symptoms feedback• Regimen based filling • Weekly packs

ResultsIncreased handling efficiency vs. dose

pouchesIncreased product safety Convenience for patientsSavings in clinic timeNurse resources released to consultative

discussions and for new patients

Case: Kuopio University HospitalReduction in treatment costs of nearly 40%

“Cost-savings of up to EUR 500 per patient each week would occur if the daily attendance for supervised drug-administration were to be entirely replaced by take-home medication using the Pharma DDSi package.”

Dr. Ulrich Tacke

Dept. Of Psychiatry and Drug Addiction Clinic

Kuopio University Hospital, Finland

Prevent Post-marketing dose reductions

Sub-optimal adherence is a serious problem in Intent To Treat studies that can lead to the failure of the trial

Both papers show that 1 drug in 4.5 has had at least a 50% fall in recommended dose since 1980 (excluding antimicrobial drugs)

Incidence of post market dose reduction is rising

1. Cross, J., Lee, H., Westelinck, A. et al. (2002). Postmarketing drug dosage changes of 499 FDA-approved new molecular entities, 1980-1999. Pharmacoepidemiology and Drug Safety 11, 439-46.

2. Heerdink, E.R., Urquhart, J. & Leufkens, H.G. (2002). Changes in prescribed drug dose after market introduction. Pharmacoepidemiology and Drug Safety 11, 447-453

“Maximum Tolerated Dose” rather than “Minimal Effective Dose” Most drugs are overdosed to « pass » ITT

High risk of dose reduction, and thus revenue reduction once on the market

NHS is using ECM• NHS funded study on the feasibility of electronically monitored blister packages in the

real world, done by Universities of Oxford and Cambridge, over a 3-month period last year. They were able to retrieve adherence data from 94% of patients enrolled and found that over 98% of patients took medication as prescribed:

• http://ecm.cachefly.net/pdf/SAPC_SAMS2v0.7.pdf

• The study concluded that using monitored blister packaging is indeed feasible for long term studies.

• The extremely high adherence rate is also (so far unpublished) evidenced in a multi-year 18-center NIH funded COPD study:

• http://www.informationmediary.com/media/more/UofMStudy.shtml

• This study is now in its extended 4th year, and the success of monitoring 100% of issued cards (over 35,000 to-date) is evidenced by the fact that the contract to supply Med-ic inlays has been renewed each year.

When should you start planning? EARLY!!!

Expect to run into some roadblocks:

• Additional planning steps for the study

• Additional costs of electronics and integration

• Insufficiently integrated packaging logistics

• Additional complexities in obtaining and managing data

• Reliability and patient acceptance

• (Perceived) legal and regulatory issues

• Fear of the unknown deriving from additional and more correct data

When should you start planning? EARLY!!!

• Some contract packagers have already developed methods of integrating smart packaging into clinical supply.

• Data management can be outsourced if IT group is overwhelmed

• Patient specific data is not recorded in package, limiting privacy concerns

Who are some ECM solution providers?

• Aardex – MemsCAP http://www.aardexgroup.com/

• IMC – Med-ic http://med-ic.biz/index.shtml

• MWV – Cerepak http://www.meadwestvaco.com

• Stora Enso – DDSi http://www.storaenso.com

•Costs are in line with other procedures and measurements of patient data taken during site visit. ( vitals, EKG, etc) •Fits into existing supply chain where blister packaging is used. No additional stability testing required.•Offers greater insight into patient dosing compliance.•Data analysis offer many advantages not feasible without the use of Electronic Monitoring of dosing. •Improve data quality and you can potentially save your company time and money.

Conclusion

Ward SmithClinical Packaging Consultantward7@fuse.net513-307-8163