Risk minimisation activities associated with risk management plans

Risk minimisation activities associated with Risk Management Plans

Evaluating effectiveness of risk minimisation activities

Dr Jane Cook

Branch Head

Post-market Surveillance Branch

Monitoring and Compliance Division, TGA

ARCS Scientific Congress 2015

6 May 2015

What are risk minimisation activities?• Initiatives that attempt to positively influence patients or health care professional

behaviours, and through these changes lead to improved patient outcomes

• Focuses on minimising harms

• Need to plan the level of change or achievement of outcome indicators that the

intervention was successful.

• A protocol for how the evaluation will occur needs to be developed and this

should specify the metrics and thresholds by which the programme success will

be measured and audited

• Should be supplied with the Risk Management Plan (RMP)

Risk minimisation activities associated with

Risk Management Plans

1

Types of risk minimisation activities

Focus on:

• Risk prevention – identifying those at particular risk through testing and not

prescribing, adjusting dose etc.

• Risk mitigation – usually relies on monitoring during therapy to identify increase

risk and allow intervention

• Neither preventable or able to be mitigated – may be acceptable depending on

risk-benefit profile



2

Tool selection

Will depend on the following factors:

• Level of risk

• Objectives of the risk minimisation activity

• The target or targets of the activity

• The characteristics of the prescribers (generalists versus specialists)

• Characteristic of potential patients – vulnerability access

• Potential variability in standards of care across regions – activity may already be embedded as

part of patient selection

A comprehensive strategy may require a range of interventions



3

Types of risk minimisation activities• Communication:

- DHCP letters/information

- Prescribing dispensing guidelines

- Patient brochures, alert cards

- Education

• Restricted access:

- Registration programmes for patients

- Certification programmes for prescribers/dispensers

- Limited pack size, repeats, dosage forms

- Dispensing linked to test confirmation

- Certain types of prescribers

- Limited to patient specific group – limited pharmacogenomic profile

• Controlled regulatory framework - scheduling



4

Risk Minimisation Programme

• You have identified the risks to be mitigated

• Selected the tools (activities) to be used in the programme

• You now need to ensure the activities will meet their objectives and be successful

in mitigating the identified risks

• You now need to develop an evaluation framework or proto



5

Areas to consider when developing a frameworkArea Description

Structure Reason for and description of the interventions and tools and their objectives

Design Key aspects, including any comparison, and duration and measures of success

Process

indicators

Those to address adequacy of the content

Those to assess adequacy of coverage, utilisation and maintenance

Outcome

indicators

Knowledge and awareness, attitudes, actual behaviours – depend on nature of activity

Those related to patient outcomes such as avoidance of C/I drugs, morbidity or mortality

measures

Analyses How measure of performance will be undertaken against pre-identified measures of

success

When will data be collected

What type of analyses will be performed



6

Programme evaluation

• Need to measure effectiveness of overall programme as well as each individual

component

• Indicators selected to evaluate the performance of the programme need to be:

– relevant

– well-defined

– sensitive

– reliable

– evidence-based

– objective

– tailored to the programme



7

Evaluation• Comprehensive evaluation of overall effectiveness should involve measuring

performance in several aspects or domains

• One methodology is the RE-AIM framework:

– Reach

– Efficacy/effectiveness

– Adoption

– Implementation

– Maintenance



8

RE-AIM

Dimensions Definition

Reach Number and representativeness of participants selected for inclusion in

evaluation the protocol

Efficacy/effectiveness What are the changes expected – behavioural, patient outcome have these

any negative consequences?

Adoption Number and representativeness of those that agree to participate – do these

continue to be representative – bias?

Implementation The degree to which the intervention has been delivered as intended (could

also consider cost)

Maintenance The extent to which the intervention has been delivered overtime as

intended



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How did the intervention succeed in the

‘real world’• Implementation fidelity

• Poor design or poor implementation?

• Good outcomes could they be better?



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Evaluating implementation fidelity

Area Description Examples of assessment methods

Exposure Were all aspects delivered to

the target recipients?

Survey, review administrative records of delivery of

elements to participants. Samples need to be

representative

Content Was what delivered the same

as originally designed? Was

the interpretation of the

materials as expected? I.e.

was messaging ‘fit for

purpose’?

Focus groups

Frequency Was it delivered consistently at

the frequency in the initial

activities plan?

Stakeholder survey, patient clinical reviews, drug utilisation

study

Duration Was it delivered consistently

throughout the activity period

Sampling as above11

Evaluating effectiveness of the risk minimisation programme

• Selecting appropriate outcome indicators

– Specific

– Measurable

– Time-bound

• Consistent with overall aim of the risk minimisation programme

• Meaningful targets from both clinical and public health perspective

• Precisely defined – hepatotoxicity versus liver failure vs hepatitis, contraindication

• Will influence sample size

• Consideration of surrogate or composite endpoints



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Characteristics of suitable outcome measures Characteristic Description

Preventable or mitigatable

Specific Clearly defined and requires little judgement

Easy to diagnose/detect Easy to identify and confirm

Rich in information Consider periodic rather than one off sampling

Responsive Is sensitive the proposed activity

Reliable Precise, reproducible, unlikely to be variable on repeated measures

Internally validity Linked to use

External validity Generalizable to general population

Clinical relevance Likely to influence treatment choices

Practical Easily implementable and low cost

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Designs• Comparator – can be difficult where has been required as part of registration

• Staggered roll out

• Before and after comparison if available

• Trend analysis through interrupted time series (periodic sampling) and use of

other existing databases e.g. health claims data

• Should confirm persistence and maintenance of the programme impact over time



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Other considerations• When would evaluation cease?

• When could the risk minimisation activity cease?



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Summary

• Life-cycle approach

• Evaluation of the parts and the whole of the risk minimisation programme

• Should be simple, pragmatic and user friendly to prevent undue clinician and

patient workload

• Measures should be clearly defined, easy to use, reproducible and practical

• Risk management programme should aim to in the real world ensure that ‘the

right prescriber provides the right medicine to the right patient, at the right dose

and right time’



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Health & Medicine

Risk minimisation activities associated with risk management plans