Oncology Treatment Guidelines :The Rules and Rationale

Oncology Treatment Guidelines :

The Rules and Rationale

Assoc. Prof. Dato’ Dr. Fuad Ismail

&

Dr. Paul Cornes

What are Clinical Practice Guidelines?

Treatment of patients in the clinical setting requires complex inputs

• Disease factors – tumour type, stage, organs involved ..

• Patient factors - age, sex, PS, …

• Treatment factors - efficacy, toxicity, cost …

Clinician cannot keep abreast with evidence now

• Published randomized controlled trials grew from 5,000 per year in

1978–1985 to 25,000 per year in 1994–2001.

IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.

ISBN 978-0-309-16422-1.

What are Clinical Practice Guidelines?

Clinical practice guidelines are statements that include

recommendations intended to optimize patient care that are informed

by a systematic review of evidence and an assessment of the benefits

and harms of alternative care options.

Clinical Practice Guidelines (CPGs) are intended to provide a

systematic aid to making such complex medical decisions

• Help decision making

• Improve healthcare outcomes

Clinical guidelines

Act to reduce variation in

practice

• Permitting effective audit of

outcomes

Improve outcomes

• By steering physicians and

patients to chose the most

clinically effective treatments

Expose areas where evidence is

poor by

• Describing the evidence used

to make a recommendation

• Using grades and strengths of

evidence

Most OECD countries could save money by improving clinical guidelines and negotiating better drug prices, BMJ 2010;341:c5552

Many Malaysian oncologists

have relied on guidelines

from the USA and EU

Historically have not formally

included value judgements

Clinical guidelines

Some guidelines

explicitly make

decisions based on

cost effectiveness

• Example UK

N.I.C.E


Erlotinib is recommended as an option

for the first-line treatment of people

with locally advanced or metastatic

non-small-cell lung cancer (NSCLC) if:

• they test positive for the epidermal growth

factor receptor tyrosine kinase (EGFRTK)

mutation

• the manufacturer provides erlotinib at the

discounted price agreed under the patient

access scheme (as revised in 2012).

Clinical guidelines

Most evidence

based guidelines

promote clinically

effective care –

which is generally

cost-effective too


Clinical guidelines save money

Kosimbei et al. Health Research Policy and Systems 2011, 9:24 http://www.health-policy-systems.com/content/9/1/24

91% of guidelines

save money

What makes a Trustworthy Guideline :

To be trustworthy, guidelines should

• be based on a systematic review of the existing evidence;

• be developed by a knowledgeable, multidisciplinary panel of

experts and representatives from key affected groups;

• consider important patient subgroups and patient preferences;

• be based on an explicit and transparent process that minimizes

distortions, biases, and conflicts of interest;

• provide a clear explanation of the logical relationships between

alternative care options and health outcomes, and

• provide ratings of both the quality of evidence and the strength of

the recommendations; and

• be reconsidered and revised as appropriate when important new

evidence warrants modifications of recommendations.

What standards are there for guidelines?

Just as we have “CONSORT” standards to report clinical trials

Guidelines have standards from the “GRADE” Working Group

– Brozek JL, Akl EA, Alonso-

Coello P, Lang D, Jaeschke R, Williams JW. et al. GRADE Working

Group, Grading quality of evidence and strength of recommendations in clinical

practice guidelines. Part 1 of 3. An overview of the GRADE approach and

grading quality of evidence about interventions.. Allergy. 2009;64669-77

– Guyatt GH, Oxman AD, Kunz R, Jaeschke R, Helfand M, Liberati A. et

al. GRADE Working Group, Incorporating considerations of resources use into

grading recommendations.. BMJ. 2008;3361170-3

“


ISBN 978-0-309-16422-1.


Standards include

• Transparency

• Conflicts of interest

• Multidisciplinary and balanced, ideally with

patient representatives

• Should use systematic reviews

• A clear description of potential benefits and

harms.

• A summary of :

– relevant available evidence (and evidentiary

gaps),

– description of the quality (including applicability),

– quantity (including completeness), and

– consistency of the aggregate available evidence


ISBN 978-0-309-16422-1. PDF is available from The National Academies Press at

http://www.nap.edu/catalog.php?record_id=13058


An explanation of the part played by values,

opinion, theory, and clinical experience in

deriving the recommendation.

A rating of the level of confidence in (certainty

regarding) the evidence underpinning the

recommendation.

A rating of the strength of the

recommendation in light of the preceding

bullets.

A description and explanation of any

differences of opinion regarding the

recommendation.


ISBN 978-0-309-16422-1. PDF is available from The National Academies Press at

http://www.nap.edu/catalog.php?record_id=13058

Proposed CPG Standards

1. Establish transparency

2. Management of Conflict on Interest

• disclosure, divestment, exclusion

3. CPG Group Composition

• Multi-displinary, patients and patient groups

4. CPG – Systemic Review Intersection

5. Evidence based rating and strength of recommendations

6. Write-up on recommendations

• Explain recommendations, summarise evidence, input values

and judgement

7. External review

8. Updating

So why not just have one world guideline?

Treatment decisions must be relevant to the patient population in

Malaysia

• Including its relative wealth

• Access to medical resources (ranked 80th in the world 2010-11)

• And reflect Malaysian Societal Values

Country Spend as

a % of

GDP

(2010-11)

Annual

Spend in US

Dollar

equivalent

Malaysia 4.4 645

USA 17.7 8,508

UK 9.4 3,405

Korea Rep 7.4 2,198

Japan 9.6 3,213

Ref: Data – world Bank. Accessed URL: http://data.worldbank.org/indicator/SH.XPD.TOTL.ZS

So why not just have one world guideline?

Ref

But Guidelines relevant to Malaysia could give

important health leadership in middle income Asia

Limitations of CPG

Variable quality of individual scientific studies;

Limitations in systematic reviews (SRs)

Lack of transparency of development groups’ methodologies

Failure to multi-stakeholder, multi-disciplinary guideline development

groups

Unmanaged conflicts of interest (COI)

Failure to use rigorous methodologies in CPG development.

Lack of evidence in subpopulations eg comorbidities, low socio-

economic groups, rare conditions.

Awareness of Guideline recommmendations

There are many guidelines

available as resources

Clinicians need to be aware of

the evidence behind the

guidelines.

May need to compare different

recommendations

ABS Guidelines for HDR In cervical cancer S Nag et al. Int. J. Rad Onc Biol. Phys., Vol. 48, No. 1, pp. 201–211, 2000

Guidelines vs Guidelines : Which do we use?

http://www.uspreventiveservicestaskforce.org/uspstf/uspscolo.htm Accessed 23 Nov 2014

http://www.uspreventiveservicestaskforce.org/uspstf/uspscolo.htm

NCCN Guideline on Cervical Cancer 2010

All recommendations are

category 2A unless stated

otherwise

Relevance of trail results versus real world

clinical practice

O’Shaughnessy J et al J Clin Oncol 20:2812-2823

Although overall survival was demonstrated, regime was

not widely used due to toxicity

Why do Malaysian guidelines advocate MDT

decisions?

Because we believe it improves outcomes and reduces

variability in treatment and improves cost-effectiveness

Evidence from UK NHS case control study

Definition of MDT

• A specialist breast surgeon operating

• on > 50 breast cancers per year.

• Plus a pathologist, oncologist, radiologist, specialist nurse.

• Evidence based guidelines.

• Formal weekly MDT meeting.

• Audit of clinical activity.

Ref: Eileen Kesson. The influence of MDT care on survival from Breast Cancer. NCIN & UKACR London, June 2011. URL:

www.ncin.org.uk/view?rid=712. Accessed Nov 20, 2014


decisions?


• Breast cancer mortality fell after MDT working introduced

• 11% lower all-cause mortality

• 17% lower breast cancer specific mortality




decisions?


• Breast cancer mortality fell after MDT working introduced

• 11% lower all-cause mortality

• 17% lower breast cancer specific mortality



Why do Malaysian guidelines advocate palliative

care expertise be available?

Palliative care process enhances patient satisfaction, quality of

care, and outcomes while reducing costs.

– Verret D, Rohloff RM. The value of palliative care.. Healthc Financ Manage.

2013 Mar;67(3):50-4.

“There are no examples of chemotherapy that save money

compared to best supportive care”

– Payne SK et al. The Health Economics of Palliative Care.

http://www.cancernetwork.com/review-article/health-economics-palliative-care-1

Payne SK et al. The Health Economics of Palliative Care. http://www.cancernetwork.com/review-article/health-economics-palliative-

care-1

Why do Malaysian guidelines advocate palliative

care expertise be available?

• OS better with novel

therapy

• QOL better

• hazard ratio for death in

the standard care

group, 1.70; 95% CI,

1.14 to 2.54; P = 0.01

Temel JS. N Engl J Med 2010;363:733-42.

Early

supportive

care

Care when

symptoms

progress

“targeted treatment”

was supportive care

How can we improve Malaysian Guidelines?

By being explicit about the clinical effectiveness of the

interventions

• In terms of clinically relevant end points – not surrogate end

points

• Overall Survival – Not DFS, PFS = Added Life Years (ALYs)

• Quality of life – Not Toxicity scores = Q

• The metric for our key endpoints; Q x ALY = QALY


By being explicit about the clinical effectiveness of the

interventions

This enables us to rank the value of potential treatment options

Tier Impact

Extremely

effective

Significant prolongation of

survival or

long term significant increase

in tumour control

Moderate

efficacy

Intermediate between the two

Minimal

efficacy

“statistically significant”

survival benefits of only short

duration

we will need payer and stakeholder consensus to

agree the parameters for our decisions !

What is the

“minimum

clinical

benefit” to

justify

treatment

from

Malaysian

Societal

perspectives?


Resource issues:

International Guidelines from the EU and USA

are freely available

• But may not be relevant from a Malaysian

perspective

Writing guidelines relevant to Malaysia takes

time and resource

• Access to medical libraries

• MDT input implies staff time will be needed

away from clinical duties

• The ability to involve stakeholders from

payers and the patient advocacy groups

Initial guidelines will require the most resource,

subsequent revisions should prove easier

How to improve Malaysian Guidelines :

Language issues

The language used in guidelines show be easily understood

Use of technical English may need to be controlled

Standards for Malaysian Guidelines

Good clinical guidelines should be:

Questions & Discussion

“Knowing is not enough; we must apply.

Willing is not enough; we must do.”

—Goethe

Health & Medicine

Oncology Treatment Guidelines :The Rules and Rationale