EBM, reductionism , and the - PowerPoint Presentation

Slide1

EBM, reductionism, and the road to Medicine’s Adaptive Pathways to Patients (MAPP).

Professor Mike

Kelly

Primary Care Unit, Institute of Public Health,

University of Cambridge.Slide2

The original precepepts of EBM.Slide3

The legacy of Archie Cochrane

Effectiveness and Efficiency

(1972)Slide4

Do we know whether intervention x for problem y is effective?

How do we know it is effective?

How do we know whether it is more or less effective than intervention z?

On what basis do we make that judgement of effectiveness?

Do we know what it costs? And is it cost effective?

If it is not cost effective, why is it still being used?

What are the dangers posed to the public of interventions and actions about which we are scientifically uncertain?

Are the interventions dangerous? Why are we using potentially dangerous or worthless interventions?Slide5

Do we know whether intervention x for problem y is effective?

How do we know it is effective?

How do we know whether it is more or less effective than intervention z?

On what basis do we make that judgement of effectiveness?

Do we know what it costs? And is it cost effective?

If it is not cost effective, why is it still being used?

What are the dangers posed to the public of interventions and actions about which we are scientifically uncertain?

Are the interventions dangerous? Why are we using potentially dangerous or worthless interventions?Slide6

Use the evidence which is the least likely to be biased as the basis for clinical decision making because -

medical interventions are inherently risky to patients;

very costly for whoever has to pay for them. Slide7

Key elements.What is the effectiveness of x compared to Y for condition z.Search the extant scientific literature.Appraise the literature with in the hierarchy of evidence.Synthesise the evidence.

Make a recommendation.Slide8

Conventional criticisms.Slow – pateints and the public expect fatsrr access.Expensive and adds burdens to payers.

Stifles innovation.

Focus on

onternal

validity.

Disease categories and the emergence of

extremen

sub- sub categories – personalised medicine. Slide9

But…..Deviations from RCTs as a gold standard not infrewquently seized upon by industry and other vested interests to sew doubt and uncertainty about an issue.Slide10

Developing public health guidelines at NICE: going beyond the EBM paradigm.The absence of trial data.The absence of evidence more geneally

– downstream rather than upstream

The impossibility of

appltying

\RCT

desigs

to some problems.

Need for diversity of methods and

disciplnes

.

Need to understand mechanisms.

How applicable are the data to the circumstances and context?

Can the scientific intervention of the trial or the study be transferred to the context of interest?Slide11

Critisisma of the pubic health approach.Devalued the gold standard.Focus on rwal world and qualitative evidence

unrelauble

and prone to

boias

.

Use of theory and models

reagarded

with suspicion – not

empirival

science.

Efforts to widen the

epitemic

base of decision making seen as unhelpful to HTA and EBM.Slide12

Reklationism vs reductionismIn public health it was necessary to focus on relations between groups within populations.It was also necessary to try to move beyond simple reductionist accounts of social phenomena.Slide13
Slide14

Back to new technologies and the appearance of the Medicines Adaptive Pathways to |Pateints (MAPP.Led by the European Medici))nes

Sgency

(EMA); MIT, NUCE,.

Appears in 2014 under the auspices of the EMA.

NEWDIGS –

Mnew

Druf

Development \P Paradigms.Slide15

Rationale.Presently con and conventionally authorisation occurs after Phase III RCTs.Ths is said to be too slow and doesn’t meet the need of stakeholders.Posy approval issues will be minimised.

Problems of co-morbidities sorted out.Slide16

MAPP Innovation.MAPP is about combining other methods with RCTs.This is in order to reduce uncertainty about benefit risk profeiles and

sto

speed access to the drugs – to reduce from 8 years to 2 years.Slide17

This will produce flexible development and access strategies.Will supposedly optimise the trade – odff between early patient access, public health and social benefits.Slide18

How MAPP works.Improved lifespan management of the technology – will involve the continuous updating of the evidence base.Monitoring improved because of more rigorous post approval.Slide19

Tiools and methods.RCTs plusreal world pragmatic RCTs, non-randomised observational studies including those based on qualitataive

methods.Slide20
Slide21

Targetted populations.Post genomic medicine, heterogeneity.Pwersonalised medicine.Slide22

Focus on patient access.Slide23

Justification.More agileand adaptive HTA process across the life cycle of the technology.Goes beyond the ICERs and QALYs and is meaningful to patients and clinicians.

Involves multilateral stakeholder dialogue.

And better involvement of patients.Slide24

Assumptions.New technologies are more effective and innovative than older ones.Current mechanisms for regulation and post approval stifle innovation (aka profit).Early market entry ids beneficial to society.

Pateints

will be content if they are taken off fast track new drugs and put back on older technologies.

Current information systems van support MAPP.Slide25

Conculsion.Paradigm losy t or paradigm regained\\?Scientific

recolution

or normal science?

The role od vested interests.

Patient harms – the shadow of Thalidomide.Slide26

Kant’s contributionAnalytic

a priori

judgements

– bringing together two things which are by definition true.

“All bachelors are men.”Slide27

Synthetic judgements

- bringing together two things by observation.

“The book is blue.”

Books can be any colour, and there are many millions of different blue objects.

Established empirically after the fact –

a posterioriSlide28

A priori synthetic judgements

Known before the fact or the observation.

Helps to make sense of novel observations.

Brings together theoretical logical understanding with past empirical observations.Slide29

These three judgement processes are used in EBMSlide30

The simplestSynthetic

a posteriori

judgements – the relative effect size of compound x over compound y in the case of disease Z.

Basic empirical observations.

Certainly subject to observational error but provides us with the basic building block. Slide31

A priori analytic judgements .

Our starting points which we determine ontologically and are by definition true.

They are rationalist because they are about the relationship between ideas.

The hierarchy of evidence and the elimination/reduction of bias belong to his class of judgements.Slide32

The RCT maximises internal validity by reducing bias

It allows the reasonable conclusion that the effect that is being witnessed is the consequence of the intervention.

By controlling out of the process factors that could contaminate the relationship between the independent and dependent variable, the observer has as much certainty as possible that the relationship is real rather than an artefact of the research process or some other variables confounding the relationship. Slide33

The hierarchy of evidence represents levels of types of evidence where internal validity is improved at each succeeding step up the hierarchy.

With each step up the hierarchy, the chances of bias are lessened.

RCTs score highly because their raison d’eˆtre is the controlling out of factors, which can cause bias.Slide34

The hierarchy of evidenceSlide35

But all of this depends on the assumption that it is possible to identify the true relationship between the between the independent and dependent variable if only we could really eliminate bias.

This is a rationalist ideal, not an empirical fact.

Kant’s distinction between phenomenon and noumenon is helpful here

as are Hume’s

comments on the fallibility of the observer.

Slide36

Synthetic a priori judgements

disease taxonomy, economic models, logic models, theory, clinical judgement and external validity.Slide37

The importance of external validity There are clear reasons to assume that what has been observed in one area where the primary studies have been carried out would apply equally well in another area.

The intervention itself is so well circumscribed that it is easy for practitioners who know nothing of the original studies to understand and implement the intervention without too much trouble and without altering the fidelity of the intervention itself.

An synthetic

a priori

judgement!Slide38

Producing evidence based guidance involves both kinds of reasoning rationalist and empiricist and all three types of judgement – the problem has been a failure to articulate these ideas, and consequently to assume that much which is scientific is merely opinion. Slide39

Introduction.Contemporary neuroscience is reawakening to ideas of the brain as a model of the world.Slide40

This paper focusses on how sense data are encoded in social interaction between the person and the external environment and how these in turn are used in generative modelling.Slide41

Conclusion.The external environment and the way it interacts with the intra – individual processes is as important as the inter- individual processes themselves. The external social and physical world is not just “there” waiting to impact on inter-individual processing and modelling either in a deterministic way or in a process akin to osmosis. Slide42

Humans actively engage with the external world and in that engagement are constrained by it in various ways. Slide43

Humans actively engage with the external world and in that engagement are constrained by it in various ways. In elucidating those interactions it is possible to describe the mechanisms linking inter and intra individual processes. Slide44

Acknowledgements.The St John’s College Reading Group on Health Inequalities and the College Annual Fund.Paul Fletcher, Natasha Kriznik, Ann Louise Kinmonth, Anil Seth.Slide45

Kelly, M.P., Kelly, R., Russo, F. (2014) The integration of social, behavioural and biological mechanisms in models of pathogenesis, Perspectives in Biology and Medicine; 57: 308-28.