Macquarie Neurosurgery Journal Club

1. MACQUARIE NEUROSURGERY JOURNAL CLUB
02/02/17
Dr Michael Mulcahy

2. MACQUARIE NEUROSURGERY
JOURNAL 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.

3. 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

4. Disclosures/Funding
• No disclosures
• Partially funded by Western Australian State Health Research Advisory
Council ($129 500)

5. 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

6. Originality
• First RCT comparing bone to titanium

7. 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

8. 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)

9. Trial Design
Eligibility criteria:
• age >18
• decompressive craniectomy + own bone available
Exclusions:
• bone flap damaged or comminuted
• intracranial infection following craniectomy
• penetrating brain injury

10. 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

11. Trial Design
Surgical procedure:
• all cases performed by S.H.
• detailed operative description

12. 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

13. Trial Design
Primary Outcome assessment

14. Trial Design
Secondary Outcome assessment

15. 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

16. Results

17. Results

18. Results
Primary outcome:
• No infections

19. Results
Primary outcome:
• 7 (22%) were deemed to have ‘complete failure’ due to bone resorption

20. Results

21. Results

22. Results

23. 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

24. 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

25. 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

26. 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