Real World Data: Cosa Sono, Come RaccoglierliGiovanni Fiori, PhD, MPH• Scientific Director, MediData Studi e Ricerche (Modena, Italy)

• Coordinator, Observational Studies Working Group, Italian Society of Applied Pharmacological Science (SSFA)

• Chairman, Late Phase Working Group, European CRO Federation (EUCROF)

Summary

Definition of Real World Data

Methodological issues in designing a RWD collection

How to face some operative constraints (e.g. manage the lack or regulations on RWD)

Real World Data

Definition– data used for decision making that are not

collected in conventional randomized controlled trials (RCTs).

RWD could be characterized by: – type of outcome (clinical, economic and

patient-reported); – hierarchies of evidence (which rank evidence

according to the strength of research design); – type of data source

ISPOR Real-World Task Force Report: Garrison et al. 2007, Value in Health; Vol.10 N. 5 pp 326-335

Outcomes Research

Research addressed to evaluate “what comesout”after an health care interventionusing measures useful for Patients and/orfor Decision Makers

“Outcome Research - the study of the end results of health services that takespatients’ experiences, preferences, and values into account - is intended toprovide scientific evidence relating to decisions made by all who participate inhealth care”Clancy CM, Eisenberg JM. Outcomes research: measuring the end results of health care. Science. 1998;282:245–246

From Efficacy to Effectiveness

Experimental

Studies

OUTCOMES

National health service’s members behavior

Diseasefeatures

Patientfeatures

Structuralfeatures

exportability

Clinicalmorbidity, symptoms,mortality

Humanisticpatient-reported symptoms, quality of life

Economicalresource use and costs

EVIDENCE

Quality of life

Patient Satisfaction

Caregivers burnout

AppropriatenessDirect medical, direct nonmedical, indirect costs

Tumor regression

Disease free survival

Overall Survival

From Effictivenessto Efficiency

EFFICACY EFFECTIVENESS

+ Safety(Large Population)

EFFICIENCY

+ Safety(Small Population)

Pre Marketing Post Marketing

EFFICIENCY

+ Pharma and Health economics

Summary

Definition of Real World Data

Methodological issues in designing a RWD collection

How to manage the lack or regulations and other operative constraints

Real World Data = Real World Evidence ?

– “Data” conjures the idea of simple factual information, whereas “evidence” connotes the organization of the information to inform a conclusion or judgment.

– “Evidence” is generated according to a research plan and interpreted accordingly, whereas “data” is but one component of the research plan.

– “Evidence” is shaped, while “data” simply are raw materials and alone are non informative.

In general, “real world evidence” is what happens to “real world data”

ISPOR Real-World Task Force Report: Garrison et al. 2007, Value in Health; Vol.10 N. 5 pp 326-335

Hierarchies of Evidence

Who’s the ugly duckling ?

Experimental Observational

Objective Tool

Clinical EpidemiologyEpidemiology and PharmacoepidemiologyPost Authorization Safety Study (PASS/PAES)Registries

Outcomes ResearchBurden of DiseaseHealth Related - Quality of LifeHealth Economics

Health Service ResearchAnalysis of Health Care ProcessesHealth Technology AssessmentMonitoring of Clinical Guidelines

New Tool Many Applications !

Not only PASS/ PAES

One Tool Many Applications

Source of RWDReal-World Data can also be categorized by type of data source.1. Databases: These include cross-sectional and longitudinal

databases which essentially provide retrospective data. 2. Patient chart reviews: Used to reflect particular insights in

patient management. 3. Patient and population surveys: Primarily for

epidemiological information. 4. Registries: patients treated at a particular centre for a

particular condition on a continuous basis. 5. Cohort studies: What most people would understand by real

life studies. 6. Pragmatic clinical trials: Whether these are strictly “real-life”

studies is open to debate

ISPOR Real-World Task Force Report: Garrison et al. 2007, Value in Health; Vol.10 N. 5 pp 326-335

ObservationalMethods

Exposition A Outcome

Time

Matched Cohort Study

Exposition B Outcome

Registries

ObservationalStudies

Registries

Registries are observational studies of patients who have a particular disease and/or are receiving a particular treatment or intervention.

They can be used for understanding natural history, assessing or monitoring real-world safety and effectiveness, assessing quality of care and provider performance, and determining value or reimbursement levels

ISPOR REAL WORLD TASK FORCE

One Registry Several Secondary Studies

DATABASE• Retrospective Cohort

Study

• Case Control Study

• Cost of Ilness• Pharmacoeconomics• Appropriateness

PATIENT REGISTRY

Summary

Definition of Real World Data

Methodological issues in designing a RWD collection

How to face some operative constraints (e.g. manage the lack or regulations on RWD)

Map of Interactions

PASS

Epidemiology• Experimental• Observational

PharmacologyPharmaco

Epidemiology

Guidelines on Good Pharmacovigilance practices (GVP), Module VIII (20/Feb/2012) – Post Authorization Safety Studies (PASS)

PharmacoVigilance

Real World Data

PASS Definition

Any study relating to an authorized medicinal product conducted with the aim of:

– identifying, characterizing or quantifying a safety hazard

– confirming the safety profile of the medicinal product

– measuring the effectiveness of risk management measures

Regulation (EU) No. 1235/2010; Directive 2010/84/EC;Guidelines on Good Pharmacovigilance practices (GVP), Module VIII (20/Feb/2012) – Post Authorization Safety Studies (PASS)

Operational Impact

20

Lack of Common EU Regulation

Country‐Specific Regulations

Riferimenti Normativi(Italia)

Studi Osservazionali sul farmaco

• Linea Guida AIFA• Linea Guida Privacy• Normativa PASS e

Farmacovigilanza

Studi Osservazionali non sul farmaco:– Epidemiologici– Qualità di Vita– Economia Sanitaria– Appropriatezza Diagnostica

• Linea Guida Privacy

Italia: Iter Autorizzativo

Tipologia Studio Iter

Studi di coorte prospettici sul farmaco(nei quali i pazienti sono inclusi nello studio in base all’assunzione di un determinato farmaco e seguiti nel tempo per la valutazione degli esiti)

Parere Unico (45 gg)

Accettazione o rifiuto dei CE satelliti (30 gg)

Altre tipologie di studi osservazionali– di coorte retrospettivi– trasversali– caso controllo– solo su casi (case cross over/case series)– di appropriatezza

Notifica ai CEPassati 60 gg:

silenzio assenso

Consenso al trattamento dati in SOs retrospettivi non è necessario qualora:

1. non sia possibile informare l’interessato per motivi etici, metodologici o per motivi di impossibilità organizzativa;

2. il programma di ricerca sia stato oggetto di parere favorevole del competente Comitato di Etica;

3. il trattamento sia autorizzato dal Garante• Dal 2012 annuale Autorizzazione Generale ma valida

solo per alcuni casi (es: non per dati genetici)

Studi Retrospettivi e Privacy

Parere favorevole del Comitato Etico competente a livelloterritoriale

Impossibilità di acquisire consenso per:– Motivi organizzativi: pericolo di alterazione dei risultati in

assenza di arruolamento di soggetti che non possonoesprimere consenso (deceduti o persi al follow up)

– Motivi etici: l’interessato ignora la propria condizione; pericolodi danno materiale o psicologico

Varie Prescrizioni:– Es: ricerca telefonica/anagrafe, rinuncia in caso di rifiuto

anonimizzazione finale, varie misure di sicuerzza, …

Autorizzazione Generale: Condizioni di Applicabilità

Conclusions

Benefits of Real World Data

Estimate long-term clinical benefits and harmsCompare multiple interventions to inform optimal therapy choicesInsight in dosing of drugs, duration and complianceExamine outcomes in diverse populationsDemonstrate full value of a product, broader range of outcomes (incl. compliance, safety, QoL)Data on resource use for economic analysesProvide evidence to public payers that product is being used in the intended target populationData if no RCT possible

ISPOR Real-World Task Force Report: Garrison et al. 2007, Value in Health; Vol.10 N. 5 pp 326-335

Patrik Sobocki (2013) ISPOR CONNECTIONS - V .19 N. 5 (pp 10-11)

Real World Evidence

For the life-science industry, the current regulatory and payer developments in Europe will have an important impact on the current form of drug development

We are likely to see a continuous generation of RWE throughout the entire life cycle of new health technologies

Real World Evidence

Building the Evidence requires the systematic unbiased collection of data

The validity of the Evidence is dependent on – the accuracy of the data – and the appropriate organization to allow

interpretation, analysis and conclusionsTransparency

Quoted by: A.M. Pleil, Senior Director Worldwide Medical and Outcomes Research - Pfizer in «Using Real World Data in Pharmacoeconomic Evaluations: Challenges, Opportunities and Approaches”

Pending Issues

Huge heterogeneity in terms and definitions

Different approaches and methodological standards

Lack of Regulations – Guidance is more dispersed, with many professional

bodies producing guidance on aspects relevant to their respective disciplines (eg. EMA vs ISPOR vs ENCePP)

Grazie dell’Attenzione