MACQUARIE NEUROSURGERY JOURNAL CLUB 02/02/17

Dr Michael Mulcahy

MACQUARIE NEUROSURGERYJOURNAL CLUB

Stephen Honeybul, David Anthony Morrison, Kwok M. Ho, Christopher R. P. Lind, and

Elizabeth Geelhoed

A randomised controlled trial comparing autologous cranioplasty with custom-made titanium cranioplasty

Journal of Neurosurgery, January 2017, volume 126, pp81-90.

Authors

• Senior author: Stephen Honeybul, neurosurgeon Sir Charles Gairdner Hospital

• David Morrison: biomedical engineer Royal Perth Hospital

• Kwok Ho: intensive care physician Royal Perth Hospital

• Christopher Lind: neurosurgeon Sir Charles Gairdner Hospital and RPH

• Elizabeth Geelhoed, professor of population health, UWA

Disclosures/Funding

•No disclosures

•Partially funded by Western Australian State Health Research Advisory Council ($129 500)

Study Relevance

• Cranioplasty after decompressive craniectomy is performed to restore cerebral protection; for cosmesis; and has been reported to improve neurologic function

• Benefits of patient’s own bone: cheap; biocompatible; radiolucent; ideal contour.

• Disadvantages: high failure rate due to infection or bony resorption

• Titanium is an alloplastic material that has been previously used due to strength and biocompatibility

• Computer-assisted design and manufacturing has made production of custom-made plates viable

Originality

• First RCT comparing bone to titanium

Aim

• To compare the long term aesthetic and functional outcomes, and the cost-effectiveness,

of primary autologous bone versus primary prefabricated titanium cranioplasty.

• Hypothesis: primary titanium cranioplasty improves cerebral protection by avoiding the

frequent problem of bone resorption requiring reoperation, and this will offset the higher

initial outlay cost of titanium plates

Trial Design

• Prospectively registered with ANZCTR (ACTRN12612000353897)

• Interventional randomised controlled trial

• Single centre, single surgeon

• Two arm, parallel group study

• Single Blinded (to patient and relatives)

Trial Design

Eligibility criteria:

• age >18

• decompressive craniectomy + own bone available

Exclusions:

• bone flap damaged or comminuted

• intracranial infection following craniectomy

• penetrating brain injury

Trial Design

Manufacture:

• based on high resolution CT

• rapid protocol 3D model of skull created

• plates manufactured from medical grade titanium, (thickness 0.6-1.0mm)

• patient identification and orientation laser marked on plate

• plate try-fitted on model to ensure smooth contour and unambiguous orientation

• standard steam sterilisation

Trial Design

Surgical procedure:

• all cases performed by S.H.

• detailed operative description

Trial Design

Primary outcome measure:

• implant failure requiring reoperation

• either infected cranioplasty requiring removal of implant or bone flap resorption

Secondary outcome measures:

• adverse events (any time in the 12 months)

• cosmetic and functional outcome (assessed by S.H. and patient/primary carer)

• total hospital costs over 1 year period

Trial Design

Primary Outcome assessment

Trial Design

Secondary Outcome assessment

Trial Design

Statistical Analysis Plan

• sample size calculation: taking p<0.05 as significant, and a power of 80% for the

study, 32 patients in each group to demonstrate a 25% difference

• this was based on S.H. experience: 32% complication rate with autologous

cranioplasty (due to infection or bone resorption) v. <5% complication rate with

titatium cranioplasty

• intention to treat analysis

Results

Results

Results

Primary outcome:

• No infections

Results

Primary outcome:

• 7 (22%) were deemed to have ‘complete failure’ due to bone resorption

Results

Results

Results

Internal Validity

Statistics:

• power calculation was appropriate (80% with p=0.05)

• 25% change in outcome is comparable to the literature of the senior surgeon

• achieved their recruitment target

• sample size calculation seems dubious

Protocol prospectively registered with ANZCTR

• note the change from double to single blinded RCT

• ?Experimenter bias

Internal Validity

Randomisation:

• 6 weeks prior to cranioplasty

• Random number sequence generated by software program

• Randomisation numbers concealed in sequentially numbered sealed envelopes

• Baseline characteristics were similar

Blinding:

• The surgeon was not blinded…he was also the clinical assessor

Subjective outcomes, though no widely used method of measuring cranioplasty success

External Validity

• Representative population

• Relevant inclusion/exclusion criteria

• The trial design is replicable

• Surgical technique is detailed, documented and replicable

• Possible that 12 months is not long enough follow up

• All surgeries performed by a senior neurosurgeon, not usually the case in public hospitals

• Titanium plates not used in MUH

Conclusion

• More revisions in the autologous bone group, but not statistically significant (p=0.053)

• Titanium cranioplasty was associated with better functional and cosmetic outcomes

than autologous bone

• There was no significant difference in health care cost

• No primary infections

• Risk of bias from unblinding of surgeon/assessor

• Overall, thoughtful and well conducted trial, though prone to bias and some limitations

on external validity, so now independent verifiability important