Posted 04 March 2016
By Zachary Brennan
The US Food and Drug Administration (FDA) on Friday released draft guidance to assist sponsors who intend to submit an investigational device exemption (IDE) to conduct clinical trials on medical devices targeting neurological disease progression, including for Alzheimer’s disease, Parkinson’s disease or primary dystonia.
“Medical devices intended to slow, stop, or reverse the effects of neurological disease face challenges with regard to collecting safety and efficacy data in a clinical study, when less invasive pharmacotherapy approaches may be better understood or more-well accepted in the clinical community,” FDA said.
Study designs for such trials, FDA says, should aim to distinguish between symptomatic benefits and disease-altering benefits, and quantify the magnitude of such benefits in terms of biomarkers and clinical outcome assessments.
Clinical outcome assessments – including patient-reported, clinician-reported and observer-reported outcomes such as symptom reduction, decreased need for medication, or improvement in functional and quality of life measures – should consist of direct quantitative measurement of the effect of a treatment upon disease progression and its impact upon the patient, FDA says.
Neurological biomarkers, meanwhile, may include biological proteins, neurotransmitters, amino acids and metabolites in the blood, cerebrospinal fluid or brain parenchyma, FDA adds. However, sponsors should submit studies for the validation of biomarker tests used in previous clinical trials when biomarkers are chosen as a metric, as “there should be well established evidence and agreement in the clinical community that the chosen biomarker test reflects a characteristic that is important to the underlying disease process and that it is associated with a clinically meaningful outcome measure.”
The agency also cautions that identifying meaningful endpoints that measure the rate of progression of a neurological disease, especially over short periods of time, like weeks or months, “can be subtle and difficult to assess.”
“Similarly, biological markers may not be accompanied by clinically meaningful observable changes. These considerations become especially important when patients forgo currently approved treatments in earlier stages of disease, and in some cases undergo a more invasive treatment, when less invasive pharmacotherapy treatments exist and may be better understood.”
And in some cases, studies may be prolonged so that disease progression can be better understood, even when other therapies exist and have proven effectiveness.
“It may be appropriate to approve an IDE application where only a subset of the eligible study subject population would accept the risks as weighed against the benefits, provided there is enough information and an adequate informed consent process in place for study patients to make informed decisions,” FDA adds. “However, if, for a certain IDE application, the risks outweigh the anticipated benefits for all subjects, FDA would disapprove the IDE application.”
Informed Consent, Labeling
FDA recommends that an informed consent document for a neurological device describe:
- the possibility that the proposed treatment may have little or no effect upon halting or delaying the progression of the disease, or could increase rate of progression
- options for discontinuing participation in the study should the subject be dissatisfied with the study
- the potential need for long-term follow up to evaluate the effect of the treatment
As far as labeling, FDA says it “must alert users to potentially injurious outcomes associated with use or misuse of the device, including a lack of clinical benefit, and must describe actions users should take to avoid potentially injurious events.”
Clinical Considerations for Investigational Device Exemptions (IDEs) for Neurological Devices Targeting Disease Progression and Clinical Outcomes