Table 3. Risk categories of PCTs involving medical products in clinical research.

Risk Category	Paradigm	Examples	Considerations
1	One or more regulated products according to approved or labeled uses	Clinical trial comparing atorvastatin versus rosuvastatin according to labeled population and dose(s) Clinical trial comparing functional and anatomic evaluation of patients with chest pain	Some labels are highly specific, which may result in a restrictive study population Likely to be low risk to study subjects In the case of devices, FDA regulations are not triggered unless safety and effectiveness are being evaluated Describes situations that would be encountered in clinical practice
2	One or more regulated products NOT according to label but according to standard of care	Study involving the use of hydralazine in heart failure Study evaluating coronary stents in acute myocardial infarction Study involving the use of amiodarone to treat atrial fibrillation	Risk profile of the product generally well understood Risk may vary according to the level of evidence supporting the “standard of care” ranging from low to high (amiodarone, apixaban) Professional guidelines are frequently discordant with product labels/approved use “Standard of care” may be variable by geography, medical specialty, or other factors Describes situations that would be encountered in clinical practice
3	One or more regulated products NOT according to label and NOT according to standard of care	Study of renal denervation for uncontrolled hypertension Study involving apixiban for anticoagulation in patients with mechanical heart valves Study of intravenous or intramuscular lidocaine for pain relief in fibromyalgia	Understanding of risk based on less experience and Likely less developed evidence base Newly approved products likely have less evidence base in unapproved indications
4	One or more regulated products for investigational use	Pivotal device studies Phase II/III drug studies	Unknown or minimally known safety and efficacy/effectiveness profile