Therapies, Research Funding, and Racial Diversity in Essential Tremor: A Systematic Review of the Literature

Abstract

Background: Essential tremor (ET) is one of the most common tremor disorders in the world. Despite this, only one medication, propranolol, is approved by the Food and Drug Administration to treat it.

Objectives: We analyzed controlled clinical trials in ET, spanning the last 50 years, to identify potential shortcomings in the therapeutic clinical pipeline.

Methods: Outcomes reviewed included demographics (specifically gender and race), therapeutic modalities, funding information, location of research, and trends over time. Clinical trials published in English were identified in scientific databases (Pubmed, SCOPUS, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from 1970 through December 2021. Included trials were prospective, either single- or double-blinded (including blinded video assessments for surgical trials), with change in limb, head, or voice tremor as the primary outcome measure.

Results: One hundred and eighty-six controlled clinical trials were accepted for extraction, including 4207 patients. Of the 145 trials that included gender, males comprised 59% of the patient population. Only 6.4% of studies provided racial demographics; in these studies, 70.5% of patients were Caucasian. The most common therapeutic modality over the past 50 years was "pharmaceutical" (56%), and the most common pharmaceutical studied was propranolol (32%). 41% of clinical trials reported no specific funding.

Conclusions: Future efforts should focus on increasing funding for clinical trial research in ET worldwide, and trials should be designed to be more inclusive of disadvantaged minorities.

Keywords: clinical trials; essential tremor; funding; gender; race; surgery; treatment.

FIG. 1

(A) Figures represent countries that published high level clinical trial data in essential tremor from 1972–2021. Of the 186 published trials, two trials were performed by more than one country. For other, see Appendix S3. (B) Controlled clinical trials in essential tremor from 1972–2021 per one million residents. Population data was used from 2020.

FIG. 2

(A) From 1972–2021, 186 controlled clinical trials have been published. (B) Published controlled trial therapeutics from 1972–1999. (C) Published controlled trial therapeutics from 2000–2021. For other, see Appendix S4.

FIG. 3

(A) A total of 106 controlled pharmaceutical trials in essential tremor were published from 1972–2021. One clinical trial was completed by more than one country. (B) A total of 61 controlled surgical trials were conducted from 1972–2021. Of note, three trials studied more than one surgical technique. For other, see Appendix S5. (C) Of the 106 pharmaceutical trials, 22 trials studied more than one pharmaceutical.

FIG. 4

(A) Of note, funding information was collected from published clinical trials and actively recruiting trials. (B) Funding sources from 1972–1999 and 2000–2021 were compared for each funding category.