FDA WARNING_LETTER - Malcolm, Matthew PhD., OTR - February 16, 2012

On May 22, 2012, the FDA issued a Warning Letter to Dr. Matthew P. Malcolm, Sponsor-Investigator of the "Repetitive Transcranial Magnetic Stimulation (rTMS) as an Adjunct to Constraint-Induced Therapy" clinical study (IDE (b)(4)) at Colorado State University. This followed an inspection from February 10-16, 2012, which identified violations of 21 CFR Part 812 (Investigational Device Exemptions) and Part 50 (Protection of Human Subjects).

Key violations include: 1. **Failure to ensure informed consent (21 CFR 50.25(a)(2) and 812.100):** All subjects signed an Informed Consent Document (ICD) that lacked FDA-required and IRB-approved information on risks (permanent hearing loss) and exclusion criteria (large-stroke lesions). The response was inadequate, lacking a procedure for ensuring correct ICD use and staff training. 2. **Failure to maintain accurate adverse event records (21 CFR 812.140(a)(3)(ii)):** Seven reported changes in subjects' health (e.g., partial arm function loss, headache, cut requiring hospital visit, blistering, thyroid cyst, low blood pressure, rash/illness) were not documented as reviewed by the investigator or reported to the IRB, DS