Procedure-Related Complications in Sham Surgeries for Parkinson's Clinical Trials: A Meta-analysis.

BACKGROUND

Double-blind, sham-controlled neurosurgical trials for neurodegenerative disorders are debated as an ethical dilemma, particularly regarding subjects randomized to the sham surgery group with general anesthesia.

OBJECTIVE

The objective of this study was to examine the safety of sham surgeries in Parkinson's disease (PD) clinical trials through complications related to the procedure.

METHODS

A systematic review and meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Rates and odds ratios (OR) were compared using random effects analysis.

RESULTS

Seven studies, all randomized, double-blind, sham surgery-controlled trials, with 309 patients with PD, were qualitatively and quantitatively analyzed: 141 patients in sham groups and 168 patients in the experimental arms of gene or cell therapy trials. Sham subjects had lower rates of gastrointestinal, positioning, incision-site, respiratory (hypoxic or hypercapnic respiratory failure), cardiovascular, thromboembolism, postoperative cognitive decline, skull fracture, and intracranial or spinal complications when compared with active treatment subjects. Sham subjects, however, had a higher rate of perioperative respiratory infections, such as pneumonia or sinusitis. Further, sham subjects were less likely to experience postoperative cognitive decline (OR, 0.23; 95% confidence interval [CI]: 0.11-0.47), intracranial or spinal complications (OR, 0.10; 95% CI: 0.01-0.75), total major morbidity (OR, 0.30; 95% CI: 0.19-0.47), or overall complications (OR, 0.59; 95% CI: 0.47-0.75) when compared with patients receiving experimental therapy.

CONCLUSIONS

Patients with PD in the sham surgery control arm of cell transplantation or gene therapy clinical trials have a low risk of procedure-related adverse events overall and fewer complications than patients in the experimental groups. There were no reported deaths attributed to sham surgery-controlled PD clinical trials. © 2023 International Parkinson and Movement Disorder Society.