Evidence and Guidelines in Diabetes Treatment

Edwin Gale

Guidelines

1. Where does judgement come from?

2. The rise of the robot physician

3. Guidelines for the politically incorrect

4. The politics of guidelines

Life is short, The Art [medicine] is long to learn,

Experience may be misleading, And judgement is difficult

Hippocrates

Where does Judgement come from?

1. Tradition

2. Authority

3. Science

4. Analysis of the evidence

5. The personal factor

Supportive Model

Based on a long-term personal relationship between patient and physician

Palliation more important than intervention

The role of the physician was often to bear witness:

Supportive Model

Based on a long-term personal relationship between patient and physician

Palliation more important than intervention

The role of the physician was often to bear witness:

“To cure sometimes, to relieve often, to comfort always”

Where does Judgement come from?

1. Tradition

2. Authority

• Individual

• Collective

• Geographical

3. Science

4. Analysis of the Evidence

5. The personal factor

Where does Judgement come from?

1. Tradition

2. Authority

3. Science

• Experiment

• Population studies

• RCTs

4. Analysis of the Evidence

5. The personal factor

Where does Judgement come from?

1. Tradition

2. Authority

3. Science

• Experiment

• Population studies

• RCTs

4. Analysis of the Evidence

5. The personal factor

What do we mean by evidence?

“The concept of „evidence-based medicine‟ has been originally formulated in the English language and it rapidly appeared that the word „evidence‟ as

used by Sackett et al was not easy to be adequately translated in other languages”…

Pierre Lefebvre

What do we mean by evidence?

The word “evidence” is used in quite different senses, to mean

• The raw material upon which a judgement is made

• The key piece of data which proves the case one way or another

… English Included!

Often used in the sense that “what I do is evidence based; what other people do is not”

More accurately, it is a technique for making best use of the information available, and for replacing circumstantial (suggestive) evidence with direct (experimental) evidence, generally obtained through RCTs

Evidence-based medicine

Evidence-based medicine works well for situations involving well-defined patient

groups, binary alternatives, and well defined outcomes…

You cannot make one good study out of 17 bad studies

Even good information is only relevant in the context (age group, inclusion criteria etc) in which that information was obtained

But…

The Evidence Gap…

“Evidence-based review … (must) … also be supplemented by value judgments, where the benefits of treatment are weighed against risks and costs in a subjective fashion ...

We realise that others may have different judgments …”

ADA/EASD Consensus, Diabetologia (2009) 52:17-30

Where does Judgement come from?

1. Tradition

2. Authority

3. Science

• Experiment

• Population studies

• RCTs

4. Analysis of the Evidence

5. The personal factor

Medical students are trained…

… to share the same knowledge base, and to think and react the same way in the same situation

The stage beyond training …

To express yourself creatively through what you do

To learn how to do better

To achieve mastery

Guidelines

1. Where does judgement come from?

2. The rise of the robot physician

3. Guidelines for the politically incorrect

4. The politics of guidelines

Obesity

Lipids

Patient Doctor

Symptoms, concerns

Advice, treatment

Before the 1970s, a disease was something that made you ill.

A disease then became something that might turn into something that made you ill

More recently, a disease became something that might turn into something that might make you ill

The Therapeutic Transition

Obesity

Lipids

Patient

Doctor

Doctor

“But I feel fine”

Advice, treatment

Patient

Patient

Big Pharma

Doctor

Professional Societies

Doctor

Public health

“But I feel fine”

Re-elected 1944 BP 200/100 Died of a massive brain haemorrhage 6 months later…

Franklin D Roosevelt (1882-1945)

“Has resulted in an average of four extra years of life”

C Lenfant, Shattuck Lecture, 2003

“The town that changed America‟s heart”

“Has resulted in an average of four extra years of life”

C Lenfant, Shattuck Lecture, 2003

“The town that changed America‟s heart”

Risk Factors

Smoking Hypertension Hyperlipidaemia Hyperglycaemia

These have the highest risk

“Has resulted in an average of four extra years of life”

C Lenfant, Shattuck Lecture, 2003

“The town that changed America‟s heart”

Risk Factors

Smoking Hypertension Hyperlipidaemia Hyperglycaemia

] The Hyperdiseases

The Hyperdiseases

Defined not by their cause, or by their mechanism, but by their consequences

All hyperdiseases have circular definitions

The level of BP/Cholesterol/BG that is harmful

Is defined as the level that does harm

Diabetes is defined by the risk of retinopathy (2 hr value after OGTT)

11 mmol/l

Retinopathy

Retinopathy

Same result in Arizona,

UK and Egypt

11 mmol/l

Diabetes is defined by the risk of retinopathy (2 hr value after OGTT)

Arterial disease

11 mmol/l

But what is the glucose threshold for arterial disease?

Arterial disease

Multiple determinants, absolute risk varies from one population to another

Arterial disease

? 11 mmol/l

The robot physician

• The treatment of hyperdisease is based upon analysis of populations

• The cut-off for benefit is hard to define

• The outcomes are probabilistic

• The patient has no symptoms

• The treatment has no visible outcome

• Diagnosis requires no skill

• Doctors aren‟t very good at it

Guidelines

1. Where does judgement come from?

2. The rise of the robot physician

3. Guidelines for the politically incorrect

4. The politics of guidelines

Guidelines …

For the politically incorrect

Guidelines: 5 politically incorrect propositions

1. If you have a guideline, you don‟t have the evidence: if you have the evidence, you don‟t need a guideline

2. Guidelines are an assertion of authority

3. Guidelines extend the boundaries of disease

4. Guidelines aspire to the point of therapeutic futility

5. Guidelines are least reliable in the evaluation of new therapies

http://www.va.gov/trm/TRMGlossaryPage.asp

What is a guideline?

“A guideline is a statement by which to determine a course of action. A guideline aims to streamline particular processes according to a set routine or sound practice. By definition, following a guideline is never mandatory. Guidelines are not binding and are not enforced”.

1. The Angelic version

Guidelines help doctors to offer the best, safest and most cost-effective treatment to their patients They are issued as a service to humanity

Why Guidelines are Issued:

2. The Satanic version

Guidelines are a statement of authority They assert the right of competing organizations to legislate for the diabetes community

Why Guidelines are Issued:

Do you doubt this assertion?

“Guidelines are a Statement of Authority”

Then ask yourself this question:

Are guidelines judged according to their scientific quality?

… or according to the status of the organization that issued them?

Are guidelines judged according to their scientific quality?

… or according to the status of the organization that issued them?

See what I mean?

“The Satanic version”

There are 3 types of guideline: Ontological Territorial Imperial

The Ontological Guideline:

“I think, therefore I exist”

René Descartes

“We issue guidelines, therefore

we exist”

Any professional organisation

The Ontological Guideline:

…the territorial guideline

…the territorial guideline

The IDF will define the metabolic

syndrome and diabetes

…the territorial guideline

The IDF will define the metabolic

syndrome and diabetes

No, EASD and ADA

will!

The Imperial Guideline:

Reclassifies previously unconsidered

biological variation as disease.

“Plus

Ultra”

Guidelines Extend Disease

Examples: Hypertension: “Prehypertension” Diabetes: “Prediabetes” Cardiology: The NSTEMI Hepatology: Fatty liver to NAFLD But the prize goes to:

Guidelines Extend Disease

Examples: Hypertension: “Prehypertension” Diabetes: “Prediabetes” Cardiology: The NSTEMI Hepatology: Fatty liver to NAFLD But the prize goes to: Nephrology: Reduced GFR of ageing becomes CKD!

“All individuals with a Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 for 3 months are classified as having chronic kidney disease, irrespective of the presence or absence of kidney damage..

NKF (2002). clinical practice guidelines for chronic kidney disease

Guidelines do not set out to reduce the boundaries of disease

They set out to increase it

See what I mean?

According to current guidelines ~95% of the extreme elderly have a cardiovascular

risk factor that requires treatment…

According to current guidelines ~95% of the extreme elderly have a cardiovascular

risk factor that requires treatment…

… because it might stop them growing old!

Guidelines: 5 politically incorrect propositions

1. If you have a guideline, you don‟t have the evidence: if you have the evidence, you don‟t need a guideline

2. Guidelines are an assertion of authority

3. Guidelines extend the boundaries of disease

4. Guidelines aspire to the point of therapeutic futility

5. Guidelines are least reliable in the evaluation of new therapies

The Therapeutic Imperative

By extending the boundaries of disease, guidelines also extend the boundaries of treatment…

The U-shaped curve

Risks of therapy >risks of disease

Risks of disease >risks of therapy

Therapeutic optimum

Guidelines define the therapeutic

maximum, not the therapeutic optimum

Risks of therapy >risks of disease

Risks of disease >risks of therapy

Therapeutic optimum

The therapeutic optimum is a one-person solution

Risks of therapy >risks of disease

Risks of disease >risks of therapy

Therapeutic optimum

Guidelines: 5 politically incorrect propositions

1. If you have a guideline, you don‟t have the evidence: if you have the evidence, you don‟t need a guideline

2. Guidelines are an assertion of authority

3. Guidelines extend the boundaries of disease

4. Guidelines aspire to the point of therapeutic futility

5. Guidelines are least reliable in the evaluation of new therapies

Guidelines and new therapies

The global market for drugs for diabetes & lipids was $70.8 billion in 2010* In 2009, an adverse comment by the ASDA/EASD Panel wrote 20% off the share price of GSK Pharmaceutical money is the oxygen upon which academic medicine depends

•IMS Health Midas, December 2010. http://www.imshealth.com/portal/site/ims

Conflicts of Interest

Professional society meetings depend upon pharmaceutical support The journals benefit from pharmaceutical support Medical education benefits from pharmaceutical support Most of us benefit from pharmaceutical support

Data access and presentation

The trials are designed by the companies The data are collected and analysed by the companies The companies decide if, where and how the data are published The companies support almost all the experts in a given area directly or indirectly

The Circuit of Influence

Experts Societies

Guidelines

Pharma

Journals

The Circuit of Influence

Experts Societies

Guidelines

Pharma

Health administrators

Journals

Audit reimbursement

What do clinicians want?

1. Access to the best available information and analysis

2. Advice as to best use of this information

3. Common standards of care

4. Best use of resources

5. Better training of young physicians

Strengths of the current system

An insistence upon good quality information The quest for better evidence Use of clinical expertise in translation of evidence into guidelines Easy access to electronic sources of information

Weaknesses

Substitutes pseudo-certainty for uncertainty

Open to competing interests (societies, industry)

“One size fits all” recommendations

Easily misused by administrators

Converts individuals into statistics

Promotes the abdication of the clinician

“The most valuable lesson that knowledge can teach us is that its creation depends

upon a continuous line of human relationships and traditions

that go far back into the past. That continuity is an unbroken thread.

It links cultures and peoples; it brings tolerance and understanding;

it delivers hope and compassion”

Richard Horton (2004)

We are the people we treat.

We are defined by the way we look after them