Table 3.

Summary of a Proposed Upgrade Natalizumab Risk Minimization Action Plan (RiskMAP), TOUCH^™‐ as it pertains to pharmacovigilance, PML, and melanoma

(1) Prescribing program 47
(1.1) Pharmacy and infusion center requirements	°All pharmacy and infusion center staff members are trained in adverse event reporting protocols such as 15‐day reporting of PML infection or melanoma occurrence, any other opportunistic infection and/or death Prior to infusion, center staff must ensure the following requirements are met: °The infusion site will complete a Pre‐Infusion Patient Checklist and confirm clearance from a prescriber Patients will be given a revised Medication Guide that has additional information on cutaneous nevi and melanoma, as well as time to read it
(1.2) Prescriber requirements	TOUCH™‐registered prescribers must agree and adhere to the following requisites for registration: °Demonstrate capability in diagnosing and managing PML, nevi, and malignant melanoma and other opportunist infections or opportunistic malignancies, or have access to specialists with this ability for referral °Provide patients with a natalizumab Revised Medication Guide °Report any cases of PML, melanoma, or hospitalization/death due to PML, melanoma, and/or any other opportunistic infection or opportunistic malignancy to the manufacturer °Evaluate patient 3 months following first infusion, 6 months following the first infusion, and every 6 months henceforth barring discontinuation of treatment, including a skin review and evaluation of all nevi for changes. °Determine every 6 months whether each patient should continue natalizumab and has not had significant nevi or other skin lesion develop and fill out the Revised Patient Status Report and Reauthorization Questionnaire
(1.3) Patient requirements	TOUCH™‐registered patients must adhere to the following conditions before being accepted for registration: °Must be TOUCH™‐registered. °Must understand the potential risks and benefits of treatment, including the increased possibility of PML infection, potential for nevi growth, and potential for melanoma development. °Revised Medication Guide must be read. °Information about concurrent medicines and treatments taken must be provided at each infusion. °Must have a baseline dermatologic evaluation
(1.4) Education Program	Educational materials on the benefits and risks associated with natalizumab, increased risk of PML, potential risks of melanoma, and requirements of the TOUCH™ program will be provided to prescribers, infusion site staff, pharmacists, and patients by the manufacturer
(2) (2.1) Healthcare provider and patient educational materials	Educational Materials and forms include the following: °Patient Revised Medication Guide and Revised Package Insert (for patients and prescribers). °Revised Patient Status Report and Reauthorization Questionnaire (filled out every 6 months by prescribers) °Revised Dear Doctor and Dear Patient Letters which include information on nevi and melanoma
(3) Reporting	The manufacturer has implemented a reporting and collection system for safety information as follows: All spontaneous and solicited adverse event reports from any postmarketing source are reported A report of all confirmed PML cases, melanoma cases, or nevi that have substantially changed are to be sent to the FDA within 15 calendar days Reports of any other serious opportunistic infections, opportunistic malignancies, and/or death must be sent to the FDA within 15 calendar days
(4) TOUCH™ safety surveillance program	The manufacturer, through TOUCH™, will systematically follow and actively solicit information regarding the occurrence of PML melanoma, and other serious opportunistic infections or opportunistic malignancies on every natalizumab‐treated patient in the U.S. The various reporting mechanisms include: ° Thorough collection and assessment of preinfusion revised patient checklists and the revised prescriber/patient enrollment form ° Thorough serious adverse event reporting ° Thorough contact with prescribers every 6 months in the form of a Revised Patient Status Report and Reauthorization Questionnaire ° Attempt to find patients who discontinued natalizumab treatment and track them for 6 months 1 The manufacturer is creating a Safety Review Committee to review safety data and determine appropriate corrective actions, if needed
(5) TOUCH™ program evaluation	The manufacturer will evaluate the effectiveness of the natalizumab RiskMAP and will report results quarterly for the first year, then every 6 months for 2 years, and annually thereafter to FDA Each FDA submission will include analyses of two major datasets: °Health outcomes data (e.g., PML rate, melanoma rate, overall safety) Systems/process data, quality, and compliance metrics