This is an article about RMPs- Risk Management Plans in PVG and important concepts to understand.
I have divided it into two parts, the first has concepts that need to be understood and are described in detail.
Whereas the second half of the article has 27 key definitions relevant to RMPs.
Let’s dive in :-)
1- Risk minimization measures:
- Risk minimization measures are interventions intended to prevent or reduce the occurrence of adverse reactions associated with the exposure to a medicine, or to reduce their severity or impact on the patient should adverse reactions occur.
- These are interventions
- Hence, by nature, episodic and on as and when required basis.
Two types of RMMs:
1- Routine RMMs
2- Additional RMMs
2- Routine risk minimization measures:
- Applicable to all products
- Basic minimum standard of PVG
- Safety concerns of a medicinal product are normally adequately addressed by routine risk minimization measures.
3- Additional risk minimization measures:
- In exceptional cases however, routine risk minimization measures will not be sufficient for some risks and additional risk minimization measures will be necessary to manage the risk and/or improve the risk-benefit balance of a medicinal product.
Each safety concern needs to be individually considered and the selection of the most suitable risk minimization measure should take into account:
- The seriousness of the potential adverse reaction
- Severity (impact on patient)
- Preventability or the clinical actions required to mitigate the risk
- The indication, the route of administration, the target population and the healthcare setting for the use of the product
- A safety concern may be addressed using more than one risk minimization measure, and a risk minimization measure may address more than one safety concern.
- Risk minimization measures should therefore guide optimal use of a medicinal product in clinical practice with the goal of supporting the provision of the right medicine, at the right dose, at the right time, to the right patient and with the right information and monitoring.
- Safety concerns should be prioritized in terms of frequency, seriousness, severity, impact on public health and preventability.
- Careful consideration should then be given to whether the goal can be reached with routine minimization activities, and, if not considered sufficient, which additional minimization measure(s) is (are) the most appropriate.
- Additional risk minimization measures should focus on the most important, preventable risks and the burden of imposing additional risk minimization should be balanced with the benefit for patients.
4- Routine pharmacovigilance:
- Set of activities required by applicable regulations as a minimum standard of pharmacovigilance to be conducted for all medicinal products.
- Minimum PVG std for all products
- Routine risk minimization activities:
- Risk minimization activities that apply to all medicinal products and relate to standard activities such as product labelling, limitations on drug pack size and the legal status of the product (e.g., drug scheduling).
Routine RMAs include PPL:
- Product labelling (L)
- Patient information leaflet (P)
- Limitations on drug Pack size (P)
- The Legal status of the product (L)
5- Additional risk minimization activity:
An intervention intended to prevent or reduce the probability of an undesirable outcome, or reduce its severity should it occur, which is in addition to the routine risk minimization activities defined as requirements applied to all medicinal products in the regulations of a particular territory.
Two key components:
- Prevention/reduction of probability of occurrence
- Reduction of severity if it occurs anyway
- This in addition to common minimum std of PVG applicable for all products
Why are additional risk minimization activities required?
- Additional risk minimization activities apply to some new medicines, or for older products where a safety issue has been identified, to improve the benefit/risk profile.
Examples of additional risk minimization activities include:
- Educational programs for HCPs, patients and care givers
- Patient screening or monitoring
- Patient alert cards (e.g. anticoagulants)
- Other more restrictive types of activities would include pregnancy prevention schemes, e.g., thalidomide, and controlled access programs, e.g. clozapine
6- Burden of Risk minimization activity:
Burden is defined as the additional load that a risk minimization activity imposes on:
(3) The healthcare system including health care professionals
(4) Other stakeholders such as regulatory authorities, pharmaceutical companies, the supply chain and those involved in access and supervision of the use of medicines.
The burden may impact, for example:
- Patients by adversely affecting their access to prescribed medicines and/or needed healthcare services, daily activities or routines.
- Healthcare providers by adding steps or services that are normally not required in the day-today management of their medical area
- The health care system by requiring extra human and/or financial resources
7- Effectiveness threshold:
Minimum acceptable level of risk minimization to be achieved in order for the intervention to be rated a success.
The effectiveness threshold is determined subjectively taking into account:
• The impact of risk
• The vulnerability of the target population
• The drug’s benefit in a given indication
• Aspects of practicality and feasibility
8- Identified risk:
An untoward occurrence for which there is adequate evidence of an association with the medicinal product of interest.
Examples of identified risks include:
- An adverse reaction adequately demonstrated in non-clinical studies and confirmed by clinical data
- An adverse reaction observed in well-designed clinical trials or epidemiological studies for which the magnitude of the difference compared with the comparator group, on a parameter of interest suggests a causal relationship.
- An adverse reaction suggested by a number of well-documented spontaneous reports where causality is strongly supported by temporal relationship and biological plausibility, such as anaphylactic reactions or application site reactions.
- In a clinical trial, the comparator may be placebo, active substance or non-exposure.
9- Potential risk
An untoward occurrence for which there is some basis for suspicion of an association with the medicinal product of interest but where this association has not been confirmed.
Examples of potential risks include:
• Toxicological findings seen in non-clinical safety studies which have not been observed or resolved in clinical studies.
• Adverse events observed in clinical trials or epidemiological studies for which the magnitude of the difference, compared with the comparator group (placebo or active substance, or unexposed group), on a parameter of interest raises a suspicion of, but is not large enough to suggest a causal relationship.
• A signal arising from a spontaneous adverse reaction reporting system
• An event known to be associated with other active substances within the same class or which could be expected to occur based on the properties of the medicinal product.
10- Important identified risk and important potential risk-
- An identified risk or potential risk that could impact on the benefit-risk profile of the product or have implications for public health. What constitutes an important risk will depend upon several factors, including the impact on the individual, the seriousness of the risk, and the impact on public health.
- Normally, any risk that is likely to be included in the contraindications or warnings and precautions section of the product information should be considered important.
11- REMS-Risk evaluation and mitigation strategy (REMS):
- Drug safety program that the U.S. FDA can require for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks.
- REMS are designed to reinforce medication use behaviors and actions that support the safe use of that medication.
- While all medications have labeling that informs health care stakeholders about medication risks, only a few medications require a REMS.
If you want to read more about REMS, you can read my article on that below:
12- Risk assessment:
- Risk assessment consists of identifying and characterizing the nature, frequency, and severity of the risk associated with the use of a product.
- Risk assessment is subdivided into risk estimation and risk evaluation.
- It therefore includes the study of risk perception and the trade-off between perceived risks and perceived benefits.
- It is defined as the appraisal of the significance of a given quantitative (or where acceptable, qualitative) measure of risk.
13- Risk communication:
- Any exchange of information concerning the existence, nature, form, severity or acceptability of health or environmental risks.
Effective risk communication involves:
- Determining the types of information that interested and affected parties need and want.
- Presenting this information to them in a useful, accessible and meaningful way.
14- Dominant risk:
- The risk that is considered to be the major contributor to the overall risk profile.
- Other terms used to describe the dominant risk are, e.g., primary risk or risk driver.
- Dominant risk is the one adverse reaction that outweighs the others in the overall risk profile and risk management of the product.
RMP-related definitions to remember and understand:
- Alert: An identified risk associated with the use of medicinal products which requires urgent measures to protect patients.
- Development pharmacovigilance and risk management plan- A plan to conduct activities relating to the detection, assessment, understanding, reporting and prevention of adverse effects of medicines during clinical trials.
- Educational tool: Material designed to impart awareness, knowledge and aid comprehension of specific information.
- Effectiveness of risk minimization: Measure of effect of risk minimization in a setting allowing for meaningful conclusions with regard to the use of a medicinal product.
- Harm: Damage qualified by measures of frequency of occurrence, severity or duration.
- Hazard: A situation or given factor that under particular circumstances could lead to harm. A source of danger.
- Informational tool: Material that is applied to bring attention or focus on information relevant to meeting risk minimization objectives.
- Risk estimation: Risk estimation includes the identification of outcomes, the estimation of the magnitude of the associated consequences of these outcomes and the estimation of the probabilities of these outcomes.
- Risk Evaluation: Risk evaluation is the complex process of determining the significance or value of the identified hazards and estimated risks to those concerned with or affected by the decision.
- Risk avoidance: An informed decision not to become involved in activities that lead to the possibility of the risk being realized.
- Risk elimination: ‘Absolute’ or complete prevention of risk, i.e. reduction of the frequency of an undesirable outcome to zero.
- Risk factor: Characteristics associated with an increased probability of occurrence of an event or disease.
- Risk identification: Determining what risks or hazards exist or are anticipated, their characteristics, remoteness in time, duration period, and possible outcomes.
- Risk level/ level of risk: Characterization of an undesirable outcome by severity and likelihood of occurrence.
- Risk management: Reiterative activities or interventions associated with the identification, characterization, prevention or mitigation of risks and the measurement of the effectiveness of the risk minimization measures.
- Risk minimization: In a broader sense the term risk minimization is used as an umbrella term for prevention or reduction of the frequency of occurrence of an undesirable outcome (see risk prevention) and reduction of its severity should it occur.
- Risk minimization action plans (RiskMAPs): FDA approved strategic safety program designed to meet specific goals and objectives in minimizing known risks of a product while preserving its benefits.
- Risk minimization-burden balance: A measure of the effectiveness of risk minimization relative to the burden it imposes.
- Risk minimization intervention / Risk minimization activity / Risk minimization measure: Application of one or more risk minimization tools with the intent to reduce the frequency of occurrence of an undesirable outcome or to reduce its severity should it occur.
- Risk minimization program- A system of risk minimization action(s) that are described and derived from a risk minimization plan.
- Risk minimization strategy- Direction and scope of planned risk minimization as specified by objective(s) and target(s) to reach defined goal.
- Risk minimization target- Recipient or audience for a risk minimization intervention instrumental to its implementation, e.g. healthcare providers.
- Risk minimization tool- A risk minimization tool is a method for delivering an intervention intended to minimize specific/specified risks.
- Risk mitigation- Reduction of the severity of an undesirable outcome should it occur.
- Risk prevention- Reduction of the frequency of occurrence of an undesirable outcome in a population, population subset or an individual patient.
- Safety Concern- An important identified risk, important potential risk or missing information.
- Safety-related outcome of interest- Clinical outcome indicator closely linked to the goal(s) of a risk minimization program which has been selected as suitable indicator of relevance for measuring its effectiveness.
That would do for now.
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Thank you for your time :)
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