Concerns have been raised about lack of efficacy or suspected resistance to anthelmintic products authorised for use in cattle and sheep but at the same time there are not large numbers of suspected lack of expected efficacy (SLEE) reports received from the livestock sector. There may be many reasons why this is the case, but one of these could be because there is a lack of understanding on how the information collected when a SLEE is reported is used by the Marketing Authorisation Holder (MAH) and the Veterinary Medicines Directorate (VMD).
The VMD, Animal and Plant Health Agency (APHA), British Cattle Veterinary Association (BCVA), Sheep Veterinary Society (SVS) and the National Office of Animal Health (NOAH) have collaborated to produce this article to explain this and encourage increased reporting of SLEEs.
A suspected lack of expected efficacy (SLEE)
Veterinary surgeons, pharmacists and suitably qualified persons as prescribers have a professional responsibility to report adverse events to the Marketing Authorisation Holder (MAH) or directly to the Veterinary Medicines Directorate (VMD). This is outlined in the RCVS code of conduct and SQP Code of Practice. Adverse events are unfavourable and unintended effects that may occur after administering a medicine, including lack of efficacy cases.
Suspected lack of expected efficacy (SLEE) is the apparent failure of an authorised product to have the expected efficacy in an animal.
Reasons to suspect a lack of efficacy in relation to anthelmintics:
The importance of reporting a SLEE
As with reporting adverse veterinary medicine events, reporting of SLEEs is critical to the ongoing monitoring activities for veterinary medicines to protect animal health, public health, and the environment. It provides real-time field information in relevant populations enabling the early identification of potential problems and allowing appropriate action to be taken.
It is important to report all SLEE cases, including those which may already be detailed on the Summary of Product Characteristics (SPC), such as cases where resistance to a particular active substance is widely accepted.
Consistent reporting of SLEE cases enables interventions at an individual, local, and country level. Data from field populations is also particularly important for monitoring anthelmintic resistance in different geographical regions.
Reasons for a lack of expected efficacy of an anthelmintic include:
- Clinical disease or death due to a suspected or proven parasitic burden, despite appropriate anthelmintic treatment
- Insufficient faecal egg count reduction (FECR) after anthelmintic treatment
- Shortened egg reappearance period after anthelmintic treatment
- Poor clinical response to treatment and/or ongoing ill-thrift/poor growth rates
- Actual reduced efficacy of the product – such as batch quality problems, anthelmintic resistance, incorrect storage or use of expired product
- Non-product related factors –such as re-infection with parasitic larvae from the pasture (particularly if there is a high pasture burden), unrealistic expectations of product efficacy against the target parasite, change in parasite species, concurrent disease, incorrect dosing/failure to administer product correctly (includes dosing at inappropriate times)
How you can report a SLEE
Anyone who is made aware of a SLEE can report it to the MAH or directly to the VMD using the online reporting form.
MAHs are legally obligated to submit all adverse events (both adverse reactions and SLEEs) that they are made aware of to the VMD, and all adverse events submitted directly to the VMD are sent to the MAH, therefore prescribers do not need to report to both. It is important to note that MAH reports and reports submitted to the VMD are both anonymised to maintain reporter confidentiality.
Minimum information required:
- Identifiable source or primary reporter – this should include the name and address of primary reporter (the prescriber or the user of the product, such as the farmer). Also, provide the initials, geographic location or another unique identifier to allow collection of further information and avoid duplication of reports, whilst fully complying with relevant data protection laws, such as General Data Protection Regulation and privacy legislation.
- Patient details – species, sex, age
- Veterinary medicine concerned – product name and marketing authorisation (MA)number
- Adverse event details – narrative of the SLEE case, including relevant dates, animal details (weights) and dose given
In addition to this minimum information, it is important that the reporter includes as much detail as possible in the report to enable a full evaluation. The reporter does not need to determine if there is a problem with the product before submitting a SLEE report.
For additional assistance or advice on reporting adverse events guidance is available here or, the VMD’s Pharmacovigilance Team can be contacted by e-mail adverse.events@vmd.gov.uk.
After submitting a SLEE report
The VMD’s Pharmacovigilance Team continuously monitors all reports of suspected adverse events (both adverse reactions and SLEEs) from authorised veterinary medicinal products that are submitted to the VMD. The VMD also monitors all reports that are sent to the MAH. If a SLEE report has been submitted to the MAH, the MAH is expected to validate the report to ensure that the minimum information required is included in the report before it is then forwarded to the VMD.
Intensive exchange of information between the MAH and the VMD, and procedures to avoid duplication (such as the unique identifier provided in reports), whilst maintaining confidentiality, ensures the quality of the systems and data.
Reports are followed-up to obtain additional information relevant to the case, if required. The VMD does not give clinical advice or individual feedback on cases in a follow-up. However, MAHs have extensive knowledge of their products and may provide further assistance and advice in a follow-up for a SLEE report to obtain additional information. In some cases, this may lead to a specific diagnosis or suggested change in management which can be immediately implemented.
Further investigations could be warranted if there is a repeating pattern or concern with a particular product which may result in further action.
After a SLEE report is evaluated
The VMD’s Pharmacovigilance Team evaluates all cases and carries out statistical analysis on the data to determine whether there are a significant number of reports with the same or similar event, which could indicate a problem with a product. When appropriate, action following a SLEE report can be taken. The VMD could look to:
- Add additional warnings on the product’s packaging
- Change the way a product is used
- Inform prescribers of the concerns (for example through letters, bulletins, or electronic media)
Products removed from the market after a SLEE report
Reporting of SLEE is vital to inform parasite control for both individual groups of ruminants, and the wider ruminant livestock sector.
Anyone that is made aware of a SLEE can report it to the MAH or directly to the VMD using the online reporting form. This will help to ensure that authorised anthelmintic products are efficacious and will inform ongoing research and testing in this disease area.
The VMD has the authority to withdraw specific batches of a product from the market if a quality defect is identified. The VMD could also revoke the marketing authorisation of a product if there is sufficient evidence in the data to show that the benefit-risk balance is no longer considered positive. However, this is unlikely to occur after a single SLEE report. However, the ability to suspend or revoke a product provides further confidence in the quality, safety, and efficacy to the end user of authorised veterinary medicines in the UK.