Upload
others
View
11
Download
1
Embed Size (px)
Citation preview
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
2 CER. 2015. JL García López, MD, MSc, PhD
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
3 CER. 2015. JL García López, MD, MSc, PhD
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
4 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Oncology …
Comparative effectiveness research (CER)
Average annual growth rates of health spending for selected functions, in real terms, OECD average, 2008 to 2011. OECD 2013
5 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Oncology …
Comparative effectiveness research (CER)
Average annual growth in pharmaceutical expenditure per capita, in real terms, 2000 to 2012 (or nearest year). OECD 2014
6 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Hemato-Oncology …
Comparative effectiveness research (CER)
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.”
7 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Hemato-Oncology …
Comparative effectiveness research (CER)
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.
8 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Hemato-Oncology …
Comparative effectiveness research (CER)
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.
9 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Hemato-Oncology …
Comparative effectiveness research (CER)
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.
10 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Hemato-Oncology …
Comparative effectiveness research (CER)
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.
11 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Hemato-Oncology …
Comparative effectiveness research (CER)
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
12 CER. 2015. JL García López, MD, MSc, PhD
- 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.
Background, Concept &
Methodologies
In Hemato-Oncology …
Comparative effectiveness research (CER)
13 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Hemato-Oncology …
Comparative effectiveness research (CER)
US 2009, Why then?
•Awareness of Complexity
•Awareness of Cost
14 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Hemato-Oncology …
Comparative effectiveness research (CER)
Awareness of Complexity (US):
- Large amount of information
- Clinical complexity: comorbidities, age, multidisciplinary
approachs, etc…
15 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Hemato-Oncology …
Comparative effectiveness research (CER)
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
16 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Oncology …
Comparative effectiveness research (CER)
17 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Oncology …
Comparative effectiveness research (CER)
18 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Hemato-Oncology …
Comparative effectiveness research (CER)
New tools:
- Computing Power
- Connectivity
- Improvements in organizational capabilities
- Collaboration between teams of clinicians
and with patients
19 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Hemato-Oncology …
Comparative effectiveness research (CER)
New vision:
20 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Hemato-Oncology …
Comparative effectiveness research (CER)
RCT: 5% cancer patients
21 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Hemato-Oncology …
Comparative effectiveness research (CER)
New vision:
22 CER. 2015. JL García López, MD, MSc, PhD
Background, Concept &
Methodologies
In Hemato-Oncology …
Comparative effectiveness research (CER)
23 CER. 2015. JL García López, MD, MSc, PhD
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.
Background, Concept &
Methodologies
In Hemato- Oncology …
June 2009
Comparative effectiveness research (CER)
24 CER. 2015. JL García López, MD, MSc, PhD
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.
Background, Concept &
Methodologies
In Hemato- Oncology …
June 2009
Comparative effectiveness research (CER)
25 CER. 2015. JL García López, MD, MSc, PhD
... 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, …
Background, Concept &
Methodologies
In Hemato-Oncology …
June 2009
Comparative effectiveness research (CER)
26 CER. 2015. JL García López, MD, MSc, PhD
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
In Hemato-Oncology …
“Pragmatic” vs “Explanatory” Randomized Clinical Trials
27 CER. 2015. JL García López, MD, MSc, PhD
In Hemato-Oncology …
“Pragmatic” vs “Explanatory” Randomized Clinical Trials
28 CER. 2015. JL García López, MD, MSc, PhD
In Hemato-Oncology …
“Pragmatic” vs “Explanatory” Randomized Clinical Trials
29 CER. 2015. JL García López, MD, MSc, PhD
In Hemato-Oncology, …
“Pragmatic” vs “Explanatory” Randomized Clinical Trials
30 CER. 2015. JL García López, MD, MSc, PhD
In Hemato-Oncology …
“Pragmatic” vs “Explanatory” Randomized Clinical Trials
31 CER. 2015. JL García López, MD, MSc, PhD
In Hemato-Oncology …
“Pragmatic” vs “Explanatory” Randomized Clinical Trials
32 CER. 2015. JL García López, MD, MSc, PhD
In Hemato-Oncology …
“Pragmatic” vs “Explanatory” Randomized Clinical Trials
33 CER. 2015. JL García López, MD, MSc, PhD
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
In Hemato-Oncology …
“Pragmatic” vs “Explanatory” Randomized Clinical Trials
34 CER. 2015. JL García López, MD, MSc, PhD
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 Hemato-Oncology …
“Pragmatic” vs “Explanatory” Randomized Clinical Trials
35 CER. 2015. JL García López, MD, MSc, PhD
In Oncology …
Observational studies
PURPOSES Pre-license Post-license
36 CER. 2015. JL García López, MD, MSc, PhD
In Hemato-Oncology …
Observational studies
METHODOLOGIES:
- Cross-sectional studies
- Case-control studies
- Cohorts studies
- Registries, EHR, etc… (SEER, …)
37 CER. 2015. JL García López, MD, MSc, PhD
In Hemato-Oncology …
Observational studies
Challenges Opportunities
38 CER. 2015. JL García López, MD, MSc, PhD
In Hemato-Oncology …
Observational studies
39 CER. 2015. JL García López, MD, MSc, PhD
In Oncology …
Observational studies
40 CER. 2015. JL García López, MD, MSc, PhD
In Oncology …
Observational studies
41 CER. 2015. JL García López, MD, MSc, PhD
In Oncology …
Observational studies
42 CER. 2015. JL García López, MD, MSc, PhD
In Oncology …
Observational studies
J Natl Cancer Inst 2014; 106: 1-3
43 CER. 2015. JL García López, MD, MSc, PhD
In Oncology …
Observational studies
J Natl Cancer Inst 2014; 106: 1-3
44 CER. 2015. JL García López, MD, MSc, PhD
In Oncology …
Observational studies
J Natl Cancer Inst 2014; 106: 1-3
45 CER. 2015. JL García López, MD, MSc, PhD
In Oncology …
Observational studies
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)
46 CER. 2015. JL García López, MD, MSc, PhD
In Oncology …
Observational studies
- 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
47 CER. 2015. JL García López, MD, MSc, PhD
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
48 CER. 2015. JL García López, MD, MSc, PhD
In Hemato-Oncology …
Economic Evaluations
49 CER. 2015. JL García López, MD, MSc, PhD
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
50 CER. 2015. JL García López, MD, MSc, PhD
Applications
& Last Remarks
Comparative effectiveness research (CER) in Oncology
51 CER. 2015. JL García López, MD, MSc, PhD
Applications
& Last Remarks
Comparative effectiveness research (CER) in Oncology
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
52 CER. 2015. JL García López, MD, MSc, PhD
Applications
& Last Remarks
Comparative effectiveness research (CER) in Oncology
Defining Patient related Outcomes
Basch E et al. JCO 2012; 30:4249-4255
53 CER. 2015. JL García López, MD, MSc, PhD
Applications
& Last Remarks
Comparative effectiveness research (CER) in Oncology
Clinical Modeling in oncology
54 CER. 2015. JL García López, MD, MSc, PhD
Applications
& Last Remarks
Comparative effectiveness research (CER) in Oncology
Applying economic evaluations in decision-making process
55
In Hemato-Oncology …
CER. 2015. JL García López, MD, MSc, PhD