más allá del ensayo clínico aleatorizado… taller de...

Más allá del ensayo clínico aleatorizado…

Taller de

Investigación en Efectividad

Comparada en Onco-hematología

José L. García López, MD, MSc, PhD

Septiembre 2015

1 CER. 2015. JL García López, MD, MSc, PhD

Agenda: Comparative Effectiveness Research (CER)

In Hemato-Oncology …

Background,

Concept & Methodologies

RWD: “Pragmatic”

Clinical Trials, Observational

Studies & Economic

Evaluations

Applications & Last Remarks


Background, Concept &

Methodologies

In Oncology …

Comparative effectiveness research (CER)

Annual average growth rate in per capita health expenditure, real terms, 2000 to 2012 (or nearest year). OECD 2014



Methodologies

In Oncology …


Annual average growth rate in per capita health expenditure, real terms, 2000 to 2012 (or nearest year). OECD 2014



Methodologies

In Oncology …


Average annual growth rates of health spending for selected functions, in real terms, OECD average, 2008 to 2011. OECD 2013



Methodologies

In Oncology …


Average annual growth in pharmaceutical expenditure per capita, in real terms, 2000 to 2012 (or nearest year). OECD 2014



Methodologies



UK, In his Harveian Oration in 2008, Professor Sir Michael

Rawlins, Chairman of the National Institute for Health and

Clinical Excellence (NICE), reasoned that we need a new

approach to analyze clinical evidence. He said that:

“Randomized controlled trials (RCTs), long regarded as the ‘gold

standard’ of evidence, have been put on an undeserved

pedestal… Observational studies are also useful and, with

care in the interpretation of the results, can provide an

important source of evidence about both the benefits and

harms of therapeutic interventions.”



Methodologies



UK, “We will put patients at the heart of the NHS,

through an information revolution and greater choice

and control.” (White Paper)

- It has become more widely accepted that patients’

assessment of healthcare interventions are an essential

component in defining value.

- Reflecting this, 2009 saw the introduction of the routine

collection of Patient Reported Outcome Measures

(PROMs) into the NHS.



Methodologies



UK, The 2010 Department of Health consultation on Value

Based Pricing (VBP) proposes a new system for innovative

medicines placed on the market from January 2014.

It recommends a system whereby NICE continues to be the world

leader in the pharmaco-economic evaluation of drugs through the

HTA process.

However, rather than applying a standard cost-effectiveness

threshold to all medicines, the Government would apply

weightings to the benefits provided by new medicines

reflecting a range of price thresholds.

These thresholds would be explicitly adjusted to reflect a

broader range of relevant factors to calculate the full value of a

new product.



Methodologies



UK, 2011. ABPI, REAL WORLD DATA.

- Recent reforms of the health system in England, including

the publication of the White Paper and the Department of

Health (DoH) consultation document on Value Based

Pricing, highlight the Government’s intention to improve

healthcare outcomes for patients.

- It is important for the pharmaceutical industry to

demonstrate that its medicines can contribute to that

improvement.

- The collection and use of RW data can enable all parties

to achieve their objectives and, ultimately, to maximize

patients’ health gains.



Methodologies



US 2009. Explaining health reform: what is

comparative effectiveness research?

Comparative effectiveness research is being discussed

as part of the national health reform debate.

The aim of comparative effectiveness research is to

improve health outcomes by developing and

disseminating evidence-based information to

patients, providers, and health care decision-makers

about the effectiveness of treatments relative to

other options. Identifying the most effective and efficient interventions has the

potential to reduce unnecessary treatments, which in turn, may

help lower costs.



Methodologies



US 2009. American Recovery and Reinvestment

Act of 2009 (ARRA) allocated $1.1 billion over

two years to expand comparative effectiveness

research at AHRQ and NIH.

The Institute of Medicine (IOM), as mandated by

ARRA, recommended 100 research areas

to be given priority for funding from ARRA.

ARRA requires the Secretary of the U.S. Department

of Health and Human Services (HHS) to consider

both sets of recommendations in directing research

funds


- Clinical research provides patients,

physicians, providers, and payers with

information on the natural history of

disease, clinical presentations of disease,

and diagnostic and treatment options.

- They also require this information to decide

how to evaluate and treat their conditions.

- All too often, the information necessary to

inform these medical decisions is incomplete

or unavailable, resulting in more than half of

the treatments delivered today without clear

evidence of effectiveness.


Methodologies





Methodologies



US 2009, Why then?

•Awareness of Complexity

•Awareness of Cost



Methodologies



Awareness of Complexity (US):

- Large amount of information

- Clinical complexity: comorbidities, age, multidisciplinary

approachs, etc…



Methodologies



Awareness of Cost (US):

- For 31 of the past 40 years, health care costs have increased at a

greater rate than the economy as a whole

- Health care costs constitute 18% of U.S. GDP

- 30% increase in personal income over the past decade effectively

eliminated by a 76% increase in health care costs

- $750B in waste



Methodologies

In Oncology …




Methodologies



New tools:

- Computing Power

- Connectivity

- Improvements in organizational capabilities

- Collaboration between teams of clinicians

and with patients



Methodologies



New vision:



Methodologies



RCT: 5% cancer patients



Methodologies



New vision:



Methodologies




CER is the generation and synthesis of

evidence that compares the benefits and

harms of alternative methods to prevent,

diagnose, treat, and monitor a clinical

condition or to improve the delivery of care.

The purpose of CER is to assist consumers,

clinicians, purchasers, and policy makers to

make informed decisions that will improve

health care at both the individual and population

levels.


Methodologies

In Hemato- Oncology …

June 2009



Key elements of the definition are:

- the direct comparison of effective

interventions

- the study of patients in typical day-to-day

clinical care

- the aim of tailoring decisions to the needs

of individual patients.


Methodologies

In Hemato- Oncology …

June 2009



... can take many forms:

- Systematic reviews of the literature are the

starting point for practice guidelines, with

meta-analysis

- Explanatory Randomized Controlled Trials:

considered gold standard

- Pragmatic Randomized Controlled Trials

- Observational Studies: Large cohorts,

prospective registries, large databases,

electronic health records, …


Methodologies


June 2009



Problems with current Clinical Trials approach:

- Time-consuming:

- Historical median time from concept approval to study

activation was 580 days.

- > 90% of industry-sponsored clinical trials experience

delayed enrollment.

- Inefficiency

- High Expenditures:

- Site monitoring absorbs 25%-30% of phase III costs

- Artifice:

- Difficulties making generalization


“Pragmatic” vs “Explanatory” Randomized Clinical Trials


In Hemato-Oncology, …



Limitations of “Pragmatic” Randomized Clinical Trials

- Difficulties to interpret from an explanatory perspective

(how biological, etiological,… mechanisms interact)

- If “real” patients are heterogeneous: invalid generability

- PRCT are difficult to fund




Key questions

- Is the treatment likely to affect relevant endpoints for

patients?

- Are these meaningful differences likely to be detectable

between the groups within the time of the trial?

- Is it financial feasible to collect the important outcomes

needed to influence clinical practice?

- Is the control arm a treatment that is commonly used in

clinical practice?




In Oncology …

Observational studies

PURPOSES Pre-license Post-license




METHODOLOGIES:

- Cross-sectional studies

- Case-control studies

- Cohorts studies

- Registries, EHR, etc… (SEER, …)




Challenges Opportunities


In Oncology …



In Oncology …


J Natl Cancer Inst 2014; 106: 1-3


In Oncology …




In Oncology …


REQUIREMENTS

Provide sufficient information in reports to allow for

assessments of internal and external validity of the

study.

Reporting guidelines for specific design can be found at the

EQUATOR NETWORK WEBSITE (www.equator-network.org)


In Oncology …


- Real patients are not treated in the same way as

in clinical trials. Shall we change current patient

management?

- Figures for every outcomes in all possible

scenarios are not available. Can we trust on

assumptions? Are they feasible?

- Can we assume financial implications of

uncertainty and heterogeneity in clinical

variables?... risk-sharing agreements?

Be prepared to face incomplete information


Making clinical decisions based on economic evaluations in Oncology …

Economic Evaluations

-Methods depending on research questions:

- Minimizing-cost analysis

- Cost-benefit analysis

- Cost-utility analysis

- Cost-effectiveness analysis

-Modeling methods depending on research questions

-Transparency describing assumptions: perspectives,

discount rates, evidence resources, follow-up times, etc…

-Sensitivity analysis: deterministic and probabilistic

-To analyze results and to discuss external validity



Economic Evaluations


Applications

& Last Remarks

Comparative effectiveness research (CER) in Oncology

APPLICATIONS -Decision-making process in cancer patients

-Diagnostic, therapeutic, etc…

-Evaluation of clinical practice in oncology: -Benchmarking -Improving Quality of the delivery of cancer patients care -Decision-making in policies

-Facilitating market access: -CLINICAL LEADERSHIP in oncology:

-Defining Value in Healthcare -Defining Patient related Outcomes -Modeling -Applying economic evaluations


Applications

& Last Remarks



Applications

& Last Remarks


Value in Healthcare: Maximización de los resultados sobre los costes, para sostener los

mejores cuidados sanitarios y el mejor acceso posible a los mismos, racionalizando la provisión

de servicios.

PACIENTE, centro del sistema

IMPLICANDO A TODOS LOS AGENTES (4-5P)

El énfasis en proporcionar los mejores resultados se sustenta:

Transparencia en los datos de los sistemas de información

Mayor implicación del paciente

Liderazgo clínico

Más integración de servicios

En ciertas circunstancias, elementos de competición, EN CALIDAD, no

en precio

Competición EN “VALOR”: CONSEGUIR LOS MEJORES RESULTADOS EN SALUD PARA EL

PACIENTE A UN COSTE DETERMINADO


Applications

& Last Remarks


Defining Patient related Outcomes

Basch E et al. JCO 2012; 30:4249-4255


Applications

& Last Remarks


Clinical Modeling in oncology


Applications

& Last Remarks


Applying economic evaluations in decision-making process

55


CER. 2015. JL García López, MD, MSc, PhD

más allá del ensayo clínico aleatorizado… taller de...

Documents