Meythaler 1999b.

Methods	Randomised, double‐blind, placebo‐controlled cross‐over trial. Setting: outpatient rehabilitation clinic, tertiary care university medical centre. Funding: Medtronic, Inc.
Participants	Total participants: 17, all 17 participants with TBI (82% male). Adults: not reported, children: not reported; age range: 10‐55 years. Inclusion criteria: aged 14‐75 years; diagnosis of severe chronic spastic hypertonia in the lower limbs (although the upper limbs could also be involved) for ≥ 6 months that was defined by a mean Ashworth score ≥ 3 in the affected limbs (≥ 1 limbs) or a mean spasm score ≥ 2 in the affected limb; either failure to respond satisfactorily to treatment with oral antispasticity medications (including baclofen and possibly diazepam, clonidine, dantrolene sodium, or a combination of these) or the occurrence of unacceptable adverse effects at effective treatment dosages. Exclusion criteria: not reported. Location of spasticity: lower extremities, upper extremities could be included, > 2 extremities affected.
Interventions	Baclofen: continuous intrathecal infusion of baclofen 50 μg. A lumbar puncture was performed at either the L3‐L4 or the L2‐L3 interspace, and 1 mL was injected. Participants also received intensive inpatient rehabilitation to benefit from the decreased motor tone or increased voluntary motor control (or both) they experience with the intrathecal baclofen. After implantation of the infusion device, all participants received intrathecal baclofen 100 μg/day continuously. Placebo: preservative‐free normal saline. Cross‐over occurred during a second outpatient clinic at least 48 hours after the initial administration.
Outcomes	Outcomes assessed at 1, 2, 4 and 6 hours post injection, 1, 3, 6, 9 months post pump placement. Primary outcome: Ashworth Scale, spasm frequency, deep tendon reflexes; adverse effects: not identified; stated "no untoward effects." Secondary outcomes: not reported. Length of follow‐up: 1 year.
Notes	No data for randomised component, prior to pump insertion. Author contacted and was attempting to locate the data; however, no further information received. "Postoperatively all patients in this study received 24 to 36 hours of intravenous vancomycin and gentamicin for prophylaxis of infection." Inclusion criteria stated minimum age of 14 years, yet at least some participants as young as 10 years.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study reported as randomised but method not described.
Allocation concealment (selection bias)	Unclear risk	Allocation concealment not described.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Neither the patient nor the investigator knew which substance was injected until after the second trial phase was completed."
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	While the authors report that the 'investigator' was blinded, it was unclear if this investigator assessed outcomes.
Incomplete outcome data (attrition bias)	Low risk	Outcome data for all participants reported.
Selective reporting (reporting bias)	Unclear risk	No published protocol.
Baseline Imbalances	Low risk	Baseline imbalances not clear but not relevant for a cross‐over trial.
Appropriate study design (cross‐over trial only)	Low risk	A cross‐over study design was reasonable due to a small sample size.
Adequate washout period (cross‐over trial only)	Unclear risk	Washout period not stated.
Other bias	High risk	Unit of analysis issue. Outcomes were analysed by looking at upper vs lower extremities. "Rather than consider each muscle separately, scores for muscle tone, spasms, and reflexes were averaged for the upper or lower extremities in each patient."