EQUITABLE and ECONOMICAL ACCESS to EFFECTIVE THERAPIES Czech Republic Essential Medicines Lists | Changing needs | Evidence based medicine Data source: Czech State Institute for Drug Control, Ministry of Interior Date: June 6, 2017 Data lock point: May 28, 2017 For more details contact Arete-Zoe

WHO ESSENTIAL MEDICINES LIST “EML” WHO EML medications represent the most efficacious, safe and cost-effective treatment options available. WHO EML is designed to meet public health systems needs, often adopted as is or adjusted for national usage.

CHALLENGES Standard of Care | Access | Interoperability | Travel | Profits WHO EML medications represent the most efficacious, safe and cost-effective treatment options available. WHO EML is designed to meet public health systems needs, often adopted as is or adjusted for national usage.

Standard of Care Based on Evidence-based practice (Best practice) Keeping up with developments in medical science Minimal competence requires continuing professional education “A diagnostic and treatment process that a clinician should follow for a certain type of patient, illness, or clinical circumstance. ” Also called best practice, standard medical care, and standard therapy Cost of Care Equitable Access Population Health Burden of Disability (QALY, QADY) Medical Negligence cases

Evidence-based practice “Evidence-based practice is the conscientious and judicious use of current best evidence in conjunction with clinical expertise and patient values to guide health care decisions.”

Evidence-based practice Knowledge creation Knowledge Dissemination Knowledge Adoption ProcessClinical researchPractice guidelines Training curricula Organization SOPs Actors Professional associations, IOM, NQF Professional media Conferences Trainings Healthcare delivery Insurers Medical schools Regulators Activities Distillation of findings from clinical research Presentations Publications Partnerships Implementation tools Cost-benefit analysis Training (Hughes, 2008)Hughes, 2008

Standard of Care Public health Consistency in care delivery Equitable access Efficacy, safety, cost-effectiveness Predictability & Planning Professional education Train to standard Interoperability Medical malpractice cases Duty, Breach of duty, Harm, Causation NICE Doctors Without Borders Surviving sepsis guidelines

Accessibility Burden of Disease Standard of Care Clinical Practice Guidelines National Circumstances WHAT Essential Medicines Lists (EML) Efficacy and safety Cost-effectiveness Meets the needs of most systems Public health systems Adequate therapy Periodic review of system needs Defined standard

International interoperability Medical support in peacekeeping, disaster relief and humanitarian operations transnational operations Multinational health care Modularity of medical treatment facilities and partnerships Medicine as industry, medical tourism Fig. 1 - Not all of these people need to be in the same room Coordination, standardization and interoperability for diagnosis and treatment Collaborative exchange of information

Population turbulence Persons found to be illegally present in the EUEU and Schengen membership

Population turbulence

Holiday and business inbound All: 9,3 million (Worldbank) | 4,7 million (MMR)WorldbankMMR EU 6,4 million (MMR) – Germans, Slovaks, BritsMMR Non-EU 2,3 million (MMR)MMR Holiday and business travel outbound EU: Croatia, Slovakia, Austria, Italy, Greece, Spain, France Non-EU: Tunisia, Egypt, Turkey, UAE, Morocco Increasing popularity of exotic destinations in sub- Saharan Africa, India, Indonesia and SE Asia Popular holiday destinations Migration PolicyMigration Policy | Eurostat | border statistics | border surveys | hotel stays | MVCR |MMR | CSZOEurostatCSZO Multiple sources of migratory data of varying quality Slovakia Croatia Italy Austria Greece Hungary Turkey France Spain Egypt Population turbulence

Migration (Frontex, 2017)

Immigration to CZ by country of origin Migration-related medical risks Protracted indirect exposure EU-wide Country-specific risks: Russia (MDR TB) The Balkans (vectors)

REFUGEES IN CZ Immigration centers EU-wide crisis since 2015 CZ indirectly exposed Bělá pod Bezdězem: Capacity: 90 Currently in use: 16 Vyšní Lhoty: Capacity: 198 Currently in use : 5 Balková: Capacity: 200 Currently in use: 54 (Google Earth) Western Balkans Route (MVČR, 2017)

SITUATION IN THE CZECH REPUBLIC Standard of Care | Access | Interoperability | Travel Suggested solutions

Availability of WHO EML in CZ Summary Of the 427 WHO EML drugs 311 are registered in CZ 292 are registered and marketed This includes Special Access 135 (32%) are unavailable Most affected classes: Parenteral nutrition components Antibacterials, immune sera Antituberculars, Antiretrovirals Antiparasitics, Antidotes Implications Availability gap overlaps significantly with drugs that are in shortage globally Essential drugs are difficult or impossible to replace, and workaround solutions are usually less effective, more toxic, and/or more costly.

Significant gaps A Parenteral nutrition components Docusate sodium (palliative care) Hydrocortisone, rectal formulation Paromomycin (Cl. Difficile) B Dextran, dalteparin Magnesium sulfate C Nitroprusside (hypertensive crisis) Hydralazine, amiloride D Miconazole, griseofulvin G Sex hormones, esp. fixed combinations J Cloxacilin, cefalexim, cefixim Kanamycin streptomycin, spectinomycin Antituberculars, antiretrovirals Immune sera – rabies, diphtheria L Dactinomycin, daunorubicin, tretinoin N Halothane, lorazepam, methadone P Antiprotozoals, anthelmintics R Cyclizine S Opthalmologicals V Antidotes – edetates, acetylcysteine, fomepizole, thiosulfate and some contrast media

Tuberculosis Main challenges: Second-line TB therapies and combination products Multidrug resistant TB (Migrants from former USSR) Counterfeits BCG vaccine (Eurosurveillance, 2017) 518 cases in 2015 (CZ)

Malaria (Eurosurveillance, 2017) 29 cases in CZ in 2015 (Státní Ústav pro Kontrolu Léčiv, 2017)

Anthelmintics Vector-borne helminthsEchinococcosis Flukes Tapeworms Round worms Filarial worms Zoonotic potential Underreported

Compassionate use Drugs that are already submitted for registration Newly authorized drugs available elsewhere in the EU Special Treatment Programs Published every quarter by the Ministry of Health All patients who meet conditions of the program Can be used by specific treatment centers Not reimbursed Individual Import Physician’s application for an individual patient Needs to be preapproved by the Agency Special application for reimbursement required Alternative options

Solutions Standards of Care Clinical Practice Guidelines Evidence-based medicine Expert opinions Training, CPE Interoperability EML Tied to SoC EML default Accessible throughout the system Reflect efficacy, safety and cost Rare conditions Drugs in shortage Epidemic potential Zoonoses Disaster medicine BCW MCM Burden of disease Globalization Drug shortages Counterfeits Global markets Other access options Treatment Standards Essential Medicines National Stockpile Regular Review

BREAKDOWN BY ORGAN CLASS Essential medicines registered and marketed As available in the Czech Republic

A – Alimentary and Metabolic System Unavailable Special Access Program Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs

B – Blood and blood-forming system Unavailable Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs

C – Cardiovascular system Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable

D – Dermatologicals Some available as compounded products Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable Special Access Program

G – Genito-urinary system and sex hormones Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable Special Access Program

H – Hormones Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable Special Access Program

J01 – Antibacterials Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable Special Access Program

J02 – Antifungals Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable Special Access Program

J04 – Antimycobacterials Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable Special Access Program First-line antituberculars

J05 – Antivirals Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable Special Access Program

J06 – Immune sera and Immunoglobulins Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable Special Access Program

J07 – Vaccines Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable Special Access Program

L01 – Antineoplastic agents Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable Special Access Program

L02 – Endocrine system L03 – Immunostimmulants L04 – Immunomodulants Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs

M – Musculoskeletal Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable

N – Nervous system: Anesthetics and Analgesics Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable

N – Nervous system Unavailable Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs

P01 – Antiprotozoals Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable Special Access Program

P – Antiparasitics: Anthelmintics and ectoparasiticides Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable Special Access Program

R – Respiratory system Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable

S – Sensory organs: Ophthalmologicals Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable Special Access Program

V – Various Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable Special Access Program

ARETE-ZOE, as a consultancy, provides solutions to complex problems in the high stakes and high consequence environment of Global Pharmaceuticals, including clinical research, healthcare informatics, and public health. We blend established, Pharma sector methodologies, innovation, and adaptations/transfers from other sectors to identify and resolve consequential practices that pose risk and often result in avoidable patient casualty. However, we are specifically, not a patient advocacy group but believe in optimizing organizational effectiveness and that smart business is agile, competitive and profitable, while intrinsically safe, secure, and resilient. We work within a global context because transnational interests influence national circumstances and choices at point of prescription. ARETE-ZOE, provides full spectrum organizational and operational risk management consultancy. Our published materials provide a glimpse of some aspects of our services to demonstrate both knowledge and ongoing participation within the Pharmaceutical Industry. Our analysis and consultancy includes all channels of misuse, diversion, counterfeiting and illicit exploitation of pharmaceuticals, medical devices, and precursor chemicals. Our advisement is to manufactures, jurisdictional entities, insurers, legislators, litigators, patients, and health care providers. ​ This scope also frequently segues into the nexus of crime and terrorism as significant influencers that undermine sector integrity differentiated from other criminal activity. Obviously, vulnerability assessment, information collection management and intelligence production supporting decision-making for risk reduction and interventions are routinely within the scope of our services as well as design and implementation of operational control measures.

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