An introduction to the Essential Medicines concept: balancing innovation with public health priorities

Transcription

1 An introduction to the Essential Medicines concept: balancing innovation with public health priorities World Oncology Forum Lugano 20 October 2017 Nicola Magrini Secretary, WHO Expert Committee on the Selection and Use of Essential Medicines, Essential Medicines Department, WHO

2 The new EML 2017

3 40 years of EML ( ) 36 pages, 20 references st Model list published, approx. 200 active substances The first list was a major breakthrough in the history of medicine, pharmacy and public health Médecins sans Frontières, 2000

4 20th EML & 6th EMLc th EML: 433 medicines 6th EMLc (children): 314 medicines 602 pages, >800 references

5 eeml: database & App ELECTRONIC DATABASE TEMPLATE ONLINE SEARCH ENGINE LINK TO WHO GUIDELINES EVIDENCE SYNTHESIS

6 2. Essential medicines why some drugs are more important than other

7 7 Essential Medicines List: Concept and Procedures Essential Medicines Guiding principle: A limited range of carefully selected medicines leads to better health care, better medicines management, and lower costs Definition: Essential medicines are those that satisfy the priority health care needs of the population Selection: Selected with due regard to disease prevalence, evidence on efficacy and safety, and comparative costeffectiveness

8 8 EML criteria (EB 109/8, 2001) Disease burden and public health need/relevance Sound and adequate data on the efficacy (on relevant outcomes), safety and comparative cost-effectiveness Absolute cost of the treatment will not constitute a reason to exclude a medicine from the Model List that otherwise meets the stated selected criteria Affordability changed from a precondition into a consequence of the selection (Hogerzeil, BMJ, 2004) WHO responsible management and oversight of CoIs 2008 WHO new Guideline Manual, adopting GRADE Other considerations: regulatory status (off-label), availability, guidelines Essential Medicines List: Concept and Procedures

9 9 Essential Medicines List: Concept and Procedures WHO EML 2015 New cancer medicines 8 May, 2015

10 Methodology to Develop Proposal for Revisions TREATMENT GOAL Cure or near cure Relevant prolongation of survival Palliation of symptoms with small benefit in survival Testicular and ovarian Leukemia and germ cell tumors Lymphomas in CML Children and Adults GTN GIST LOW PRIORITY Metastatic Pancreatic Cancer Stage III Ovarian Cancer Low Medium High Slide credit: Dr. Gilberto Lopes Metastatic Bladder Cancer INCIDENCE OF DISEASE Early-Stage Breast Cancer Early-Stage Colon Cancer Metastatic Breast Cancer Metastatic Prostate Cancer Metastatic Lung Cancer HIGH PRIORITY MEDIUM PRIORITY

11 Diseases Addressed ADULT CANCERS AML and APL (adult+ped) GTN ALL PEDIATRIC CANCERS CLL Head and neck cancer Burkitt lymphoma CML Hodgkin lymphoma Ewing sarcoma DLBCL Kaposi sarcoma Hodgkin lymphoma Early stage breast cancer Metastatic breast cancer Osteosarcoma Early stage cervical cancer Metastatic colorectal cancer Retinoblastoma Early stage colon cancer Metastatic prostate cancer Rabdomyosarcoma Early stage rectal cancer Nasopharyngeal cancer Wilms tumor Epithelial ovarian cancer Follicular lymphoma GIST Non-small cell lung cancer Ovarian germ cell tumors (adult+ped.) Testicular germ cell tumors (adult+ped)

12 12 EML comprehensive cancer review: Essential Medicines List: Concept and Procedures methodology The cancer WG discussed thresholds for clinical benefits and acknowledged their importance but did not endorse an explicit threshold The EC discussed magnitude of benefit as the main criterion to include a medicines in EML but was out of its mandate to define a threshold for clinical benefit

13 13 EML comprehensive cancer review: Essential Medicines List: Concept and Procedures methodology 16 new medicines were added to the EML (out of a total of 22 requested) for 29 cancer types The cancer WG and the WHO Expert Committee used magnitude of clinical benefits to select medicines and regimens (though an explicit threshold was not endorsed) Several medicines included in EML were cost effective AND unaffordable: this will require new actions to increase access

14 14 WHO EML (cancer) application: prominent methodological challenges Common shortcomings Inconsistent use of evidence Emphasis on relative effects and p values Magnitude of benefits uncertain; Confidence in estimates and risk of bias not reported Harms under-reported Essential Medicines List: Concept and Procedures Potential improvements Link between recommendation and supporting evidence Privilege to absolute differences and net benefits Summary of findings tables Survival (disease-free) median time; 95% CIs Observational data from cohort of exposed patients Balance between efficacy/safety RCTs data and real-life observational data on tolerability

15 New EML cancer medicines main criterion: 15 magnitude of absolute benefits Imatinib: vast majority of patients in remission at 7 yrs Rituximab (large B cell lymphomas): 15% absolute increase in survival rates (from 50-55% to 70%) Trastuzumab: early stage breast cancer: up to 13% increase in survival in high risk women (from 37% to 50% survival rates at 3-6 yrs) Bendamustine, ATRA, Acknowledged as cost-effective AND unaffrodable Essential Medicines List: Concept and Procedures

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17 17 Lancet editorial October 24, 2015 Essential Medicines List: Concept and Procedures

18 Linking EML to Health System Capacity Access to cancer medicines Gaps identified in health system capacity EML in context of (i) national strategy; (ii) financing mechanism; (iii) trained workforce 1. National strategy: EML & WHO review of NCCPs & NCD plans 14/30 (47%) mention EML or treatment protocols 9/30 (30%) specify procurement and supply chain strategy 7/30 (23%) have HTA mechanism Strengthen national planning with technical assistance

19 Linking EML to Health System Capacity 2. Financing mechanisms High out-of-pocket payment, financial catastrophe (60-80% in SE Asia) Inefficient budgetary allocation, poor planning Costing platform to support prioritization, estimate package impact & health system costs 3. Workforce strategies Insufficient trained medical oncologists, nurses pharmacists, etc Providers poorly distributed, majority in capitals WHO tool to optimize workforce and implement short-term capacity building strategies

20 Medicines through Lens of Health System WHO List of Essential Medicines WHO List of Priority Medical Devices for Cancer Management Basic package of services for UHC Health system capacity

21 WHO EML 2017 Cancer medicines What s next

22 WHO EML 2017 Cancer medicines Recommendations Dasatinib (CML) Nilotinib (CML) Zoledronic acid (bone metatsteses) Fentanyl (transdermal) Methadone (already listed for substitution treatment) Rejections/standby Enzalutamide (prostate) Trastuzumab emtansine (breast) TKIs, crizotinib, (NSCLC) Tramadol (cancer pain)

23 WHO EML 2017: enzalutamide

24 WHO EML 2017: TDM1

25 WHO EML 2017 Cancer medicines The Committee did not recommend listing for: enzalutamide for metastatic prostate cancer; tyrosine kinase inhibitors (erlotinib, gefitinib and afatinib) and ALK inhibitor (crizotinib) for non-small cell lung cancer; trastuzumab emtansine for metastatic breast cancer. The Committee considered that listing of these medicines was premature and recommended the establishment of an EML cancer medicines working group to coordinate comprehensive evaluation of cancer medicines for the EML.

26 WHO EML 2019 Cancer medicines The Expert Committee recommended the establishment of an EML cancer medicines working group to coordinate comprehensive evaluation of available treatment options, across treatment lines and including recently approved medicines. The working group should support WHO in establishing guiding principles, clarifying what constitutes a clinically relevant therapeutic effect, for granting the status of essential medicine to a cancer medicine.

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28 EML Cancer medicines Where is the rub? Hamlet To sleep perchance to dream: ay, there's the rub!

29 EML Cancer medicines Where is the rub? Hamlet Only a few (10-20%) of the newly registered cancer medicines are highly effective Prices are disproportionately high and unrelated to the magnitude of benefit New mechanism should/can be put in place to increase access to essential medicines

30 to protect and promote public health. It was for this reason that we developed a concept capable of sprouting policies based on sober science, reason and peoples. Dr Halfdan Mahler, /10/2017 Title of the presentation 30