Problem:Problem:Therapy MalTherapy Mal--Compliance or Compliance or

NonNon--Adherence ...Adherence ...(Therapie(Therapie--ontrouw ...) ontrouw ...)

If a patient does not comply to the doctor’s or pharmacist’s instructions

concerning continuation, dosage andinterval of the medication, we speak of

“Mal- or Non-Adherence”

Non-Adherence, (Therapie-ontrouw),

is an Issue as old as Medicine …

Non-Adherence, (Therapie-ontrouw),

is an Issue as old as Medicine …

Non-Adherence is a problem that predates Hippocrates, who advised his fellow physicians to "keep watch for that fault in patients which

makes them lie about the taking of things prescribed."

Non-Adherence is a problem that predates Hippocrates, who advised his fellow physicians to "keep watch for that fault in patients which

makes them lie about the taking of things prescribed."

HippocratesHippocrates (460(460--377)377)Early Warning of the NonEarly Warning of the Non--AdherenceAdherence--IssueIssue

HippocratesHippocrates (460(460--377)377)Early Warning of the NonEarly Warning of the Non--AdherenceAdherence--IssueIssue

Penicillin:

The Gift from the Gods …

Penicillin:

The Gift from the Gods …

The Gift from the Gods …The Gift from the Gods …

However:

“If there were a cure for non-adherence -a pill that would make you take your other

pills - it would be a greater boon to health than any medication since penicillin” …

“Medicine’s stealthiest problem” 1999

However:

“If there were a cure for non-adherence -a pill that would make you take your other

pills - it would be a greater boon to health than any medication since penicillin” …

“Medicine’s stealthiest problem” 1999

5NonNon--Adherence to Therapy: The Doomsday Machine Similarity …?Adherence to Therapy: The Doomsday Machine Similarity …?

Concurrent Therapy: The Doomsday Machine …?

Improving Patient’s Therapy AdherenceImproving Patient’s Therapy Adherencevisvis--aa--visvis

Preventing Colossal Costs & Wastage Preventing Colossal Costs & Wastage through simple innovations …through simple innovations …

June 10, 2014Willem Kort, Confrérie Clinique

Zorg 2025, Rabobank, Amsterdam Economic Board

8From Dr. Strangelove …From Dr. Strangelove …

9

Homo Sapiens ...?Homo Sapiens ...?

10

Homo Sapiens ...?Homo Non-Adherent!

Homo Sapiens ...?Homo Non-Adherent!

“If there were a cure for non-compliance - a pill that would make you take your other pills - it would be a greater boon to

health than any medication since penicillin …”Dr.Craig Saxton, fmr Head Pfizer HQ R&D, New York, USA.

Dr. Koop

“Medicines don’t work in patients who don’t take them …”Dr.C. Everett Koop, frmr Surgeon General, USA.

Dr. Koop

Negative Effects of Mal-Compliance for Specific Drugs

Antidepressiva Serious Rebound Phenomena

Beta Blockers Rebound Hypertension, TachycardiaCa-Antagonists Reflex tachycardia at „restart“Antibiotics New „resistant“ infectionsAntiarrhythmica Life threatening arrhythmias

Anti Hypertensives Stroke and myocardial infarctionImmunosuppressants in organ transplantation

Organ rejection

Anti Diabetica Blood circulation problems

None, or less, therapeutical efficacy of the medication!

Researched by Dr.Dr.med. Joerg Dellbruegge

M.Mitzel:”Defining the Problem of Malcompliance”

“In Flagrante Delicti …”

Counseling, education and behaviour modification techniqueshave achieved only limited success

in boosting compliance ...

40% Of patients will experience treatment failure or a new

medical problem as a result of improper use of medication …

Of all medication prescribed, Of all medication prescribed, only 60% are actually consumed ...only 60% are actually consumed ...

analysis | status otcm | technology | roll out

Giga Costs ...Giga Costs ...

17Play ZDF “Heute Magzine” life-action storyboard?

Non-Adherence … The Very Costly Facts of Trash Medication.

Non-Adherence … The Very Costly Facts of Trash Medication.

Yes No

18NonNon--compliance: many patients take drugs incorrectly, infrequently, compliance: many patients take drugs incorrectly, infrequently,

or not at all. Rates & reasons vary between therapeutic areas. or not at all. Rates & reasons vary between therapeutic areas.

Source: The Hidden Epidemic by Boston Consulting Group, 2003

19NonNon--compliancecompliance::

a major a major problemproblem in in minorminor & & seriousserious illnessesillnesses, i.e. , i.e. ……

Source: PWC, Pharma 2020, 2007

20From Dr. Strangelove …From Dr. Strangelove …

RFID

Radio Frequency IDentification

NFC

Near Field Communications

24Anatomy of the (actual) Technology Principle …Anatomy of the (actual) Technology Principle …

Printed circuitry Printed circuitry ––“conductive lines”“conductive lines”

Printed Printed AntennaAntenna

Mini cellMini cellBatteryBattery

Microchip:Microchip:•• MemoryMemory•• RFID interface (NFC)RFID interface (NFC)•• Clock calendar (counter)Clock calendar (counter)•• Sensor inputsSensor inputs

Smartblister Label attachedincludes the electronic therapy adherence measurementcircuitry

Label can be attached to theexisting blister and returnedinto the original box (secondaryPackaging)

Wireless communication at the Pharmacy’s reader/programmerand with the patient’s Smartphone

SmartblistersSmartblisters in Original (secondary) Packaging …in Original (secondary) Packaging …

26Scenes we’d like to see (3): transfer of data by standard NFC cell …Scenes we’d like to see (3): transfer of data by standard NFC cell …

27Example: NonExample: Non--Compliance of Medication Taking in Compliance of Medication Taking in DiabetesDiabetes--IIII

Compliance events recording

Outcome measurements (i.e. blood glucose levels)

Confidential

Live at Work Now ...Live at Work Now ...

29From Dr. Strangelove …From Dr. Strangelove …

Live (clinical) trials: 2005Live (clinical) trials: 2005--2006, the onset ...2006, the onset ...Evidence of Functionality ...Evidence of Functionality ...

Live (clinical) trials: 2007Live (clinical) trials: 2007--2010, 2 theses (Jekle, Zeiter)2010, 2 theses (Jekle, Zeiter)Evidence of Functionality ...Evidence of Functionality ...

Prof. Dr. Irene Krämer, Prof. Dr. Irene Krämer, University of MainzUniversity of MainzPharmacy Department Pharmacy Department Johannes GutenbergJohannes Gutenberg--University University HospitalHospitalMainz, GermanyMainz, Germany

Conclusion:Effective therapy adherenceleads to regular, tied INRvalues in chronic patients.MEDICCINE enhances thestatus required.

Pharmaceutical CareResearch Group

Live (clinical) trials: 2007Live (clinical) trials: 2007-- ongoing (2 theses, Walter, Boeni)ongoing (2 theses, Walter, Boeni)Evidence of Functionality ...Evidence of Functionality ...

Polymedication Electronic Monitoring System (POEMS): Introducing a new technology as gold standard for therapy

adherence measurement.

Prof. Dr. Kurt E. Hersberger, Prof. Dr. Kurt E. Hersberger, Dr. Isabelle Arnet,Dr. Isabelle Arnet,University of BaselUniversity of BaselDepartment of Pharmaceutical Department of Pharmaceutical Sciences, Pharmaceutical Sciences, Pharmaceutical Care, Basel, SwitzerlandCare, Basel, Switzerland

Prof. Dr. med Rudolf BruppacherDr. Markus Lampert

Markus Messerlieidg. dipl. pharm

Fabienne Boenieidg. dipl. pharm

Philipp Waltereidg. dipl. pharm

Pilot “Efficiency & Wastage of Returned Medication”,Pilot “Efficiency & Wastage of Returned Medication”,Evidence of Evidence of Functionality re: Functionality re: T⁰T⁰--Monitoring ...Monitoring ...

Prof. Dr. Prof. Dr. ToineToine EgbertsEgberts, , Prof.DrProf.Dr. Marcel . Marcel BouvyBouvy, , University University of Utrecht,of Utrecht,Department of Pharmaceutical Department of Pharmaceutical Sciences, Pharmacotherapy, Sciences, Pharmacotherapy, Utrecht UMCU, NetherlandsUtrecht UMCU, Netherlands

Dr. Bart van den Dr. Bart van den BemtBemt, Principal Investigator, Principal Investigator

Live (clinical) trials:Live (clinical) trials:Evidence of Functionality ...Evidence of Functionality ...

• First trial in NL, University of Maastricht, Netherlands• Benefit Project, Vienna, Austria, BMGFJ & BMVIT• Clinical Studies Johannes Gutenberg University, Mainz, Germany• Clinical Studies Basel University, Basel, Switzerland• Projects at Sanofi Aventis, Montpellier, France• Projects at Janssen Johnson&Johnson CTI, Beerse, Belgium• Clinical Studies at Cologne University, Cologne, Germany• Clinical Studies at University of Western Australia, Crawley, Australia• Projects at BMS Bristol Myers Squibb, Utrecht, The Netherlands• Projects at Abbvie, Hoofddorp, The Netherlands• Projects at Radboud University, Nijmegen, The Netherlands• Projects at Leiden University, Leiden, The Netherlands• Projects at Utrecht University, Utrecht, The Netherlands• Projects at MediZorg HomeCare, Houten, The Netherlands

Cooperation & Associates …

• Co-operation with NXP, (Sony), regarding dedicated NFC/RFID chip and active RFID/NFC labels (Schreiner Medipharm), and Alu foils

(AMCOR)

• Novartis, Basel – East-Hanover, Barcelona, Australia

• Sanofi Aventis – Montpellier, Paris, France

• TEVA – Opava, Czech Republic - Israel

• BMS Bristol - Myers Squibb, Utrecht, Netherlands

• Janssen Pharmaceutica Johnson &Johnson – Beerse, Raritan, San Diego, Vienna

• Basel University – Basel, Geneva, Zürich, Lausanne, Bern, St. Gallen

• MSD Merck & Co., Haarlem, New Brunswick

Cooperation & Associates …

• Johannes Gutenberg Universität - Co-operation on Clinical R&D –Clinical Phamacological Vigilance, Mainz, Germany

• Sandoz – Basel, Almere, USA

• Abbvie – Amsterdam, Abbott Park, Chicago, USA

• Boehringer Ingelheim – Ingelheim am Rhein, Weesp

• Mediq - Utrecht, Netherlands

• SMK, Sint MaartensKliniek, Ubbergen, Netherlands,Radboud Universiteit, Nijmegen, Netherlands

• Transposafe, BradyCorp – Sassenheim, Milwaukee, WI

•MediZorg – Houten, The Netherlands, Benelux

•Market potential Medication Blisters –Worldwide estimation 2012: 35 Billion medication blister packages per year …

•Market potential Medication Bottles –Kaiser Family Foundation’s Report Prescription Drug Trends: 3.4 Billion prescription (medication) bottles per year …

•Market potential Licenses Pharma & Packagers -More than 400 therapeutical chemicals (groups), per therapeutical group 1 exclusive license …

•Financial Worth Healthcare Packaging by 2018 –Report Pharmaceutical Packaging Market(MarketsandMarkets) $ 80 Billion p.a.

Global Market …Global Market …

•

•

•

They ‘They ‘veve put their money where their mouth is …put their money where their mouth is …

••

••••

••

•“Geen Terugbetaling, Geen Markt” …Ron de Graaff

•“Willen, Kunnen, Mogen” … Bob van der Kamp

En En dandan nu: nu: WieWie gaatgaat datdat regelenregelen & & betalenbetalen? …? …