Translating Evidence into Practice

Professor John R Zalcberg

Head of Cancer Research Program

School of Public Health and Preventive Medicine

DEFINE

2014 2015 2016 2017 2018 2019 2020

USA TRIAL

TRIAL ANALYSED ABSTRACT PUBLISHED

GUIDELINES

AUSTRALIAN PRACTICE

EVIDENCERADAR CHANGE

Why do trials here?

DEFINE

2014 2015 2016 2017 2018

AUSTRALIAN TRIAL

TRIAL ANALYSED ABSTRACT PUBLISHED

AUSTRALIAN PRACTICE

CHANGERESULTS

Why do trials here?

DEFINE TRIAL

Topgear trial

ECC x3

ECC x2

Sx

Chemo/XRT

ECC x3

ECC x3Sx

Randomise

XRT = radiation therapy

Sx = surgery

Chemo

Chemo

Chemo

Chemo

Hypothesis

• Participation and conduct of a clinical trial

changes clinical practice independently of any

new finding that may result from the trial.

Osteoporotic vertebral fractures

• 1 in 4 women and 1 in 5 men > 50 yrs

• 50,000 new cases/year in Australia (700,000 US)

• ⅓ to ½ will result in severe pain & disability

• generally heal within a few weeks or months

• no effective treatments currently available

• high risk of further vertebral fracture within a year

– untreated osteoporosis, single VF ~ 20% risk (1 in 5)*

– treated with bisphosphonates ~ 10% risk (1 in 10)

*Lindsay R, Silverman SL, Cooper C, et al. Risk of new vertebral fracture in the year following a fracture. JAMA 2001;285:320-3.

Vertebroplasty

Bone cement (e.g. poly methylmethacrylate) injected into fracture under radiological guidance

Dramatic increase in vertebroplasties

Gray D, Hollingworth W, Onwudiwe N, Deyo R, Jarvik J. Thoracic and lumbar vertebroplasties performed in US Medicare enrollees, 2001-2005. JAMA. 2007;298(15):1760-2.

Lad S, Patil C, Lad E, Hayden M, Boakye M. National trends in vertebral augmentation procedures for the treatment of vertebral compression fractures. Surgical Neurology. 2008

Gray et al Spine 2008. Nation-wide and State-specific primary vertebroplastyrates per 100,000 Part B fee-for-service

PUBLISHED : 14 OCTOBER 2004 | THE

AUSTRALIAN FINANCIAL REVIEW | JILL MARGO

“Every now and then a treatment comes along that delivers almost miraculous results in properly selected patients. This is now happening with a treatment for a particular form of back pain that is caused by osteoporosis…”

Pre- and post-Vertebroplasty pain scores (30 uncontrolled studies, 7 prospective)

Hochmuth K, et al. Eur Rad 2006;16: 998-1004.

Pre: Mean 8.1 (6.4 to 9.7)

Post: Mean 2.6 (1.7 to 3.9)

Amount injected not describedSerious complications < 1% (23 studies)

Bone cement leakage 41.2%

(7 to 81%) (20 studies) but >98% asymptomatic

One or more possible explanations

OR

• Natural history

• Biased assessment of outcome (e.g., high

by doc. and patient)

• Placebo response

• Vertebroplasty is highly effective

Randomised, stratified by• centre (x 4)• gender • duration of symptoms (< or ≥ 6 weeks)

Either vertebroplasty or sham procedure

Participants, outcome assessors, investigators (except treating radiologist) all blinded to treatment allocation

Design

Results

No important baseline differences between groups

Participants in both groups improved to amodest degree

No evidence of a beneficial effect of vertebroplasty over sham treatment for painful vertebral fractures at 1 week, 1, 3 or 6 months

“….How do these morons get this published? Buchbinder is a socialist charlatan.

She is better suited to practice medicine in China or Cuba - unfortunately they

probably wouldn't give her a license in either of those countries….”

“I can only hope that one or both of them actually will suffer from a fracture of this

type and are denied this valuable tool to relieve the pain and prevent further

deformity. It appears that would be the only event that would stop them on their

highly focused mission of eliminating these procedures altogether.”

An example of the types of emails I receive

Some changes…

• Withdrawal of reimbursement– Blue Cross Blue Shield, USA – Ontario HTAC, Canada– Australia MSAC, Nov 1, 2011

• Guidelines– American Academy Orthopaedic Surgeons

(AAOS) strong recommendation against its use, Sept 2010

Recommendation 8We recommend against vertebroplasty for patients who present with an osteoporotic spinal compression fracture on imaging with correlating clinical signs and symptoms and who are neurologically intact.Strength of Recommendation: Strong

PRESS RELEASE“By making a strong recommendation against the use of vertebroplasty, the group is expressing its confidence that future evidence is unlikely to overturn the results of these trials [i.e., the sham controlled trials].”

When experience clashes with evidence

PUBLISHED : 13 MAY 2010 | THE AUSTRALIAN FINANCIAL REVIEW | JILL MARGO

Many treatments are introduced into medical practice prematurely, before they

have been scientifically evaluated.

Two studies have turned vertebroplasty (VP) on its head.