1. 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 https://www.aretezoe.com/

2. 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. https://www.aretezoe.com/

3. 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.

4. Standard of Care Based on Evidence-based practice (Best practice) Keeping up with developments in medical science Minimal competence requires continuing professional education https://www.aretezoe.com/ “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

5. Evidence-based practice https://www.aretezoe.com/ “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.”

6. Evidence-based practice https://www.aretezoe.com/ 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

7. 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 https://www.aretezoe.com/

8. 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 https://www.aretezoe.com/

9. 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 https://www.aretezoe.com/ Coordination, standardization and interoperability for diagnosis and treatment Collaborative exchange of information

10. Population turbulence https://www.aretezoe.com/ Persons found to be illegally present in the EUEU and Schengen membership

11. Population turbulence https://www.aretezoe.com/

12. 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 https://www.aretezoe.com/ 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

13. Migration https://www.aretezoe.com/ (Frontex, 2017)

14. 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) https://www.aretezoe.com/

16. 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) https://www.aretezoe.com/

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

18. https://www.aretezoe.com/ 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.

19. 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 https://www.aretezoe.com/

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

21. Malaria (Eurosurveillance, 2017) 29 cases in CZ in 2015 (Státní Ústav pro Kontrolu Léčiv, 2017) https://www.aretezoe.com/

22. Anthelmintics Vector-borne helminthsEchinococcosis Flukes Tapeworms Round worms Filarial worms Zoonotic potential Underreported https://www.aretezoe.com/

23. 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 https://www.aretezoe.com/

24. Solutions https://www.aretezoe.com/ 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

25. https://www.aretezoe.com/ BREAKDOWN BY ORGAN CLASS Essential medicines registered and marketed As available in the Czech Republic

26. A – Alimentary and Metabolic System Unavailable https://www.aretezoe.com/ Special Access Program Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs

27. B – Blood and blood-forming system https://www.aretezoe.com/ Unavailable Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs

28. C – Cardiovascular system https://www.aretezoe.com/ Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable

29. D – Dermatologicals Some available as compounded products https://www.aretezoe.com/ 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

30. G – Genito-urinary system and sex hormones https://www.aretezoe.com/ 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

31. H – Hormones https://www.aretezoe.com/ 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

32. J01 – Antibacterials https://www.aretezoe.com/ 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

33. J02 – Antifungals https://www.aretezoe.com/ 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

34. J04 – Antimycobacterials https://www.aretezoe.com/ 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

35. J05 – Antivirals https://www.aretezoe.com/ 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

36. J06 – Immune sera and Immunoglobulins https://www.aretezoe.com/ 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

37. J07 – Vaccines https://www.aretezoe.com/ 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

38. L01 – Antineoplastic agents https://www.aretezoe.com/ 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

39. L02 – Endocrine system L03 – Immunostimmulants L04 – Immunomodulants https://www.aretezoe.com/ Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs

40. M – Musculoskeletal https://www.aretezoe.com/ Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable

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

42. N – Nervous system Unavailable https://www.aretezoe.com/ Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs

43. P01 – Antiprotozoals https://www.aretezoe.com/ 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

44. P – Antiparasitics: Anthelmintics and ectoparasiticides https://www.aretezoe.com/ 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

45. R – Respiratory system https://www.aretezoe.com/ Numbers represent SUKL ID rather than Registration number, that is including all available forms and dosages and including Special Treatment Programs Unavailable

46. S – Sensory organs: Ophthalmologicals https://www.aretezoe.com/ 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

47. V – Various https://www.aretezoe.com/ 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

48. 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. https://www.aretezoe.com/

49. References World Health Organization. (2015). The Selection and Use of Essential Medicines. Report of the WHO Expert Committee, 2015 (including the 19th WHO Model List of Essential Medicines and the 5th WHO Model List of Essential Medicines for Children). WHO Technical Report Series No. 994 (1st ed.). World Health Organization. Retrieved from http://apps.who.int/iris/bitstream/10665/189763/1/9789241209946_eng.pdfhttp://apps.who.int/iris/bitstream/10665/189763/1/9789241209946_eng.pdf Eurosurveillance. (2017). Surveillance Atlas. Atlas.ecdc.europa.eu. Retrieved 27 May 2017, from http://atlas.ecdc.europa.eu/public/index.aspx?Instance=GeneralAtlas http://atlas.ecdc.europa.eu/public/index.aspx?Instance=GeneralAtlas Státní Ústav pro Kontrolu Léčiv. (2017). Státní ústav pro kontrolu léčiv. Sukl.cz. Retrieved 28 May 2017, from http://www.sukl.cz/http://www.sukl.cz/ Moffett, P., & Moore, G. (2011). The Standard of Care: Legal History and Definitions: the Bad and Good News. Western Journal Of Emergency Medicine, 12(1), 109-112. http://dx.doi.org/PMC3088386http://dx.doi.org/PMC3088386 Otranto, D., Dantas-Torres, F., Brianti, E., Traversa, D., Petrić, D., Genchi, C., & Capelli, G. (2013). Vector-borne helminths of dogs and humans in Europe. Parasites & Vectors, 6(1), 16. http://dx.doi.org/10.1186/1756-3305-6-16http://dx.doi.org/10.1186/1756-3305-6-16 Štěpánek, í. (2017). Dovolená v roce 2015: nejistota za hranicemi, Češi objeví Česko - iDNES.cz. iDNES.cz. Retrieved 27 May 2017, from http://cestovani.idnes.cz/turisticke-trendy-pro-rok-2016-dij-/kolem-sveta.aspx?c=A151128_181235_kolem-sveta_hig http://cestovani.idnes.cz/turisticke-trendy-pro-rok-2016-dij-/kolem-sveta.aspx?c=A151128_181235_kolem-sveta_hig Connor, P. (2016). Illegal migration to EU rises for routes both well-worn and less-traveled. Pew Research Center. Retrieved 27 May 2017, from http://www.pewresearch.org/fact-tank/2016/03/18/illegal-migration-to-eu-rises-for-routes-both-well-worn-and-less-traveled/ http://www.pewresearch.org/fact-tank/2016/03/18/illegal-migration-to-eu-rises-for-routes-both-well-worn-and-less-traveled/ Frontex. (2017). Risk Analysis for 2017 (1st ed.). Warsaw: Frontex. Retrieved from http://frontex.europa.eu/assets/Publications/Risk_Analysis/Annual_Risk_Analysis_2017.pdf http://frontex.europa.eu/assets/Publications/Risk_Analysis/Annual_Risk_Analysis_2017.pdf European Commission. (2016). Europe without borders The Schengen area (1st ed.). European Commission. Retrieved from http://ec.europa.eu/home- affairs/sites/homeaffairs/files/e-library/docs/schengen_brochure/schengen_brochure_dr3111126_en.pdfhttp://ec.europa.eu/home- affairs/sites/homeaffairs/files/e-library/docs/schengen_brochure/schengen_brochure_dr3111126_en.pdf MVČR. (2017). Aktuální statistiky - Aktuální informace o migraci. Mvcr.cz. Retrieved 27 May 2017, from http://www.mvcr.cz/migrace/clanek/aktualni- statistiky.aspxhttp://www.mvcr.cz/migrace/clanek/aktualni- statistiky.aspx NATO. (2017). Medical support. NATO. Retrieved 28 May 2017, from http://www.nato.int/cps/en/natohq/topics_49168.htmhttp://www.nato.int/cps/en/natohq/topics_49168.htm Navy Medicine. (2017). Cite a Website - Cite This For Me. Navymedicine.navylive.dodlive.mil. Retrieved 28 May 2017, from http://navymedicine.navylive.dodlive.mil/files/2012/11/KAF-Role-3-OR_web.jpg http://navymedicine.navylive.dodlive.mil/files/2012/11/KAF-Role-3-OR_web.jpg Strauss, D., & Thomas, J. (2009). What Does the Medical Profession Mean By “Standard of Care?”. Journal Of Clinical Oncology, 27(32), e192-e193. http://dx.doi.org/10.1200/jco.2009.24.6678 http://dx.doi.org/10.1200/jco.2009.24.6678 Migrant crisis: Migration to Europe explained in seven charts - BBC News. (2017). BBC News. Retrieved 31 May 2017, from http://www.bbc.com/news/world- europe-34131911http://www.bbc.com/news/world- europe-34131911 MVCR. (2017). Cizinci s povoleným pobytem - Ministerstvo vnitra České republiky. Mvcr.cz. Retrieved 31 May 2017, from http://www.mvcr.cz/clanek/cizinci-s- povolenym-pobytem.aspxhttp://www.mvcr.cz/clanek/cizinci-s- povolenym-pobytem.aspx Hughes, R. (2008). Patient safety and quality. Rockville, MD: Agency for Healthcare Research and Quality.Patient safety and quality https://www.aretezoe.com/