015 礼来风险文件Lilly Risk Management

Lilly Risk Management Risk Management is the continuous process of assessing and characterizing a product's risks and taking any necessary steps to communicate and manage those risks. These activities are undertaken to optimize the benefit/risk balance of the medication and improve individual patient outcomes. Through a continuous evaluation of risks and implementation of risk minimization activities, the risk management process ensures that information that may impact the benefit/risk balance of a medication is appropriately communicated to physicians and their patients. Lilly's role in risk management centers is to help healthcare providers make informed decisions about: · How and when a drug product should be used · How to monitor the patient for potential adverse events We also help healthcare providers effectively communicate to the patient on the proper use of the medication. Healthcare providers have an essential role in minimizing the risks for their patients. Physicians must stay informed of emerging safety information, evaluate the credibility of the information they receive, and translate the information into the proper context to make the best possible prescribing decision for their individual patient. Benefit-risk balance We know that "safety" is a relative concept and decisions about a particular drug's use must be evaluated as a balance between the benefits and risks of the medication use for an individual patient. What is Benefit? Benefits are positive outcomes or favorable effects associated with a drug. Benefits may be assessed relative to other similar products. Benefits may be due to a drug having greater efficacy, treating a broader range of patients or symptoms, or being easier for a patient to use. Benefits are measured and characterized by clinical trials, but may differ when considered from the perspective of each individual patient. Once approved, Lilly may conduct or support additional clinical trials to further measure benefits for new uses or in new populations. What is Risk? Pharmaceutical risks are undesirable or harmful events related to a drug therapy. They may be documented or suspected; common or rare; severe or merely irritating; preventable or endured. We characterize the risks associated with medicines along several dimensions to understand their meaning and significance. · To what degree is the drug viewed as the cause of an adverse event? · How severe are these risks? · How likely are these risks? · What is the longevity of the risk? Does risk increase over time? Does risk persist after the medication is halted? · How preventable are risks? · How certain are we about the information used to characterize risks? Assessing the Benefit/Risk Balance When the regulatory agency approves a drug for marketing it concludes that the drug's benefits outweigh its risks for the conditions outlined in the product label. This conclusion is based on the conclusion that there is a public health benefit from the medication. On its own, this data does not predict whether an individual patient will specifically benefit from a particular medicine. When prescribing a medication, a physician must make an individual benefit/risk evaluation, based on a drug's potential to benefit an individual patient outweigh its potential risks. Once therapy is initiated, the patient must be monitored to evaluate the benefit/risk balance based on how the drug actually performs for the individual patient. Even as physicians become experienced at identifying individual patients that will more likely benefit from a specific drug therapy, it is still not always possible to predict whether the drug will have the expected therapeutic benefit or whether side effects will occur in an individual patient. Learning how individual patients react to a medication is essential for the ongoing development of better treatment practices. Providing feedback to Lilly by reporting adverse events is a key part of Lilly's ongoing pharmacovigilance (safety monitoring) process. Information on adverse events is collected, monitored and evaluated by Lilly. Lilly collects, monitors, and evaluates drug safety information in an effort to help healthcare providers stay current with what is known about the safety of a medication. This is intended to help healthcare providers make the best possible decision on the use of a particular medication for their patients, and how to best monitor its use once the patient is started on therapy. Factors Determining Benefit/Risk · What is the expected and actual (individual) benefit for a specific patient? · What is the weight of evidence that supports that a risk exists? (how much uncertainty exists)? · How serious is the risk (including sequelae)? · How often is it that the risk will occur? · Is the risk preventable? · Will it decrease/disappear after a drug is stopped or will the risk increase over time · Does the risk outweigh the benefit? · Are there any other treatment options (drug or non-drug) where the benefit/risk balance is more favorable or less favorable? · What are the risks of the disease or condition if not treated? Risk Management Plan A Risk Management Plan systematically outlines Lilly's pharmacovigilance process for a medication, describing the ongoing activities designed to identify, characterize, minimize, and communicate product risks. Lilly includes a Risk Management Plan for every medication as part of its New Drug Application that is submitted for regulatory approval The Risk Management Plan outlines the specific risk assessment and risk minimization activities (if needed) associated with the medication. The primary purpose of a Risk Management Plan is to proactively and systematically describe a set of specific safety monitoring and evaluation activities designed to identify, characterize, and minimize and/or prevent risks that may occur with the use of a particular medication. After a drug receives approval and is made available to patients, the Risk Management Plan continues to be updated as additional information becomes available that impacts the safety profile or benefit/risk balance of the product. Updates are submitted to the regulatory authorities. What are the elements of a Risk Management Plan? · Identifies the important established or potential risks on the basis of non-clinical, clinical and post-marketing data · Outlines how the risks will be monitored for further evaluation (e.g. by conducting additional studies, monitoring of existing databases) · Specifies how the risk will be mitigated through a risk minimization plan. This plan describes a set of activities for minimizing the identified or potential risks of a product in order to optimize the benefit/risk balance. Risk evaluation & mitigation plan What is a REMS? The primary goal of a Risk Evaluation and Mitigation Strategy (REMS) is to help patients and physicians understand the known or potential risks associated with a drug and to mitigate, or lessen, the chance that a serious adverse reaction might occur. Beginning in 2008, the FDA has required these plans for certain drugs with potentially serious risks. REMS are intended to ensure that the benefits of a drug outweigh the risks. In essence, REMS provides the FDA and drug companies with an iterative, stepped framework for managing risks. Which step a product will occupy depends on its specific risk, the tools to help lessen the risk, and whether or not the tool is required by the FDA for the product's benefits to outweigh its risks. Such an approach is not a single event, but a dynamic approach to managing risk throughout the product's lifecycle by increasing or decreasing the elements of the strategy. When is a REMS Required? FDA Amendments Act of 2007 provided the FDA with new authority to more effectively manage the risks of drugs, both before and after a medication's approval, including the ability to require Risk Evaluation and Mitigation Strategies (REMS), in certain circumstances. There are a number of conditions in which REMS may be required. Most commonly, REMS are required when new safety information becomes available to make certain that the benefits of the medication outweigh its risks. The FDA may also require REMS for a group of medications that all have a similar risk - those from the same drug class, such as serotonin-reuptake inhibitors or anti-epileptic drugs. The FDA can also require REMS when a new medication is approved and there is a concern about a known or potential side effect. Review a list of drugs deemed to have an approved REMS. This includes a list of REMS for all FDA approved drugs, including non-Lilly medications. In regards to a medication, "new safety information" is defined as: · Information derived from a clinical trial · Spontaneous adverse event reports · A post-approval study · Peer reviewed biomedical literature · Other scientific data deemed appropriate about a risk or unexpected risk associated with the use of the drug. "New safety information" is an important trigger in assessing a product's benefit/risk profile and making a determination on whether or not a REMS is needed. What impact does REMS have on administration of the drug? Drug information is provided in labels (package inserts) that accompany a drug product, which is reviewed and approved by regulatory agencies, such as the FDA. This information is the primary tool to describe the benefits and risks for physicians and patients. The Medication Guide is used to help explain important risks to patients. For many years, the FDA has required Medication Guides for certain prescription drugs with serious risks. A part of REMS, the FDA can require a Medication Guide be provided so that patients can learn about a serious side effect or be reminded about special directions on how to take a drug for it to be most effective. Medication Guides, however, do not take the place of discussing a patient's medical condition and use of the drug with their healthcare provider. Patients should read the medication guide that is included with the prescription drugs to ensure they are aware of important risks. A Medication Guide is an example of one tool that helps communicate risk as part of REMS. Other tools, such as Dear Healthcare Professional letters, help inform healthcare providers as well. This information is shared with healthcare professionals to support them in providing information to patients. For prescription drugs that have a very serious known risk, such as effects on a fetus, others special requirements may be included in the REMS. This may include a specific, mandatory laboratory test before a patient can receive the medication. REMS may require that a medication only be administered to a patient in a specific setting, such as a hospital. Healthcare providers are trained to administer these special requirements and will instruct patients on what to do when these programs are necessary to ensure appropriate management of serious risks. What are the elements of REMS? REMS may require any number of specific elements, such as: · A Medication Guide · Communication Plan with healthcare providers · Dear Healthcare Professional Letter · Introductory brochure for healthcare providers and/or patients, · Product website · Educational materials disseminated via professional associations and scientific meetings · Additional measures may be required, if necessary, to address serious known risks and assure safe use of a medication. These may be implemented to allow access to drugs proven effective but with associated risks. Without these interventions to assure safe use, these medications might not otherwise be made available to patients or withdrawn from the market. Additional requirements may include: · Healthcare providers who prescribe the drug have particular training or experience or are specially certified · Pharmacies, practitioners, or healthcare settings that dispense the drug are specially certified · The drug be dispensed only in certain healthcare settings, such as hospitals · The drug be dispensed to patients with evidence of safe-use conditions, such as laboratory test results · Each patient using the drug be subject to monitoring · Patients using the drug be enrolled in a registry How does the FDA know if the REMS is working? The legislation that gave the FDA the authority to require REMS also requires that pharmaceutical companies report to the FDA on a regular basis about their REMS. Three scheduled reports are required after the FDA approves the REMS: 18 months, three years and seven years. The drug company must report on the success of the REMS and whether the REMS need to be modified, based on the assessment.