Table 4 Potential risks and adequacy of protection from risks

Physical risk: low to moderate

 ● Blood draw: possible pain associated with needle stick, ecchymosis, or phlebitis

 ● Randomization: subject assignment to the therapeutic group may be less beneficial and associated with more adverse events than standard of care

 ● Other possible risks: osteomyelitis, cellulitis, dermatitis, eczema, rash, allergic reaction

 ● Potential severe but rare risks: cessation of heartbeat and respiratory failure

Psychological risk: low

 ● However, no direct causal relationship has been established to therapy with Timoptic-XR®. These rare AEs may include depression, confusion, anxiety, disorientation, nightmares, somnolence, insomnia, diminished concentration, hallucinations

Social risk: low

 ● Subjects are required to visit the clinic weekly, which may take time away from other activities and tiredness while waiting for weekly office visits

Economic risk: moderately low

 ● Cost of travel to and from weekly appointments. Due to frequency of visit, subjects may lose time from work. Note: subjects would be required to travel for weekly visits regardless of whether the subject had been enrolled in the study, since standard of care typically requires weekly visits

Physical risk: low

 ● All subjects in the study will have their personal information confidentially secured in locked filling cabinets and with protected passwords in a computer database. Access is strictly limited to authorized individual (principal investigator, research staff, or other regulatory authorities such as representatives of FDA or IRB).