Supporting Scientific information for UK SMIs

Technical limitations

Limitations of UK SMIs

The recommendations made in UK SMIs are based on evidence (for example sensitivity and specificity) where available, expert opinion and pragmatism, with consideration also being given to available resources. Laboratories should take account of local requirements and undertake additional investigations where appropriate. Prior to use, laboratories should ensure that all commercial and in-house tests have been validated and are fit for purpose.

Specimen containers

UK SMIs use the term ‘CE marked leak proof container’ to describe containers bearing the CE mark used for the collection and transport of clinical specimens. The requirements for specimen containers are given in the EU in vitro Diagnostic Medical Devices Directive (98/79/EC Annex 1 B 2.1) which states: ‘The design must allow easy handling and, where necessary, reduce as far as possible contamination of and leakage from, the device during use and, in the case of specimen receptacles, the risk of contamination of the specimen. The manufacturing processes must be appropriate for these purposes (1)’.

Selective media in screening procedures

Selective media which does not support the growth of all circulating strains of organisms may be recommended based on the evidence available. A balance therefore must be sought between available evidence and available resources required if more than one media plate is used.

Avidity

Avidity measures antibody maturity by determining the binding strength of antibody-antigen interactions. IgG avidity tests may be used as an additional diagnostic tool especially in patients with IgM test reactivity. Avidity is initially low after primary infection and increases over time, usually about 3 months. High IgG avidity suggests that infection occurred over 3 months ago. Low or moderate IgG avidity results should not be interpreted as diagnostic of recently acquired infection, as low or moderate avidity antibodies may persist for many months following infection in some individuals. Health care providers and clinical laboratories involved in pregnancy care should be aware that avidity testing is an adjunct to the other tests and should be interpreted with consideration of the other serological tests and ideally earlier results.

Troubleshooting

When discrepant results are found these should be reviewed in accordance with the recommendations of the kit manufacturer. In certain instances consideration should be given as to whether they should be referred to the MHRA.

Uncertainty of measurement

Uncertainty of measurement expresses (attempts to quantify) the doubt that inevitably exists when any measurement is made. In most circumstances, this relies on statistical data from repeated measurements that allow one to state the degree of confidence that a measured value lies within a certain range. In order to provide a measure of confidence in results produced by a laboratory, it is necessary to identify all factors which may contribute to variation in a process and assess their potential to influence uncertainty. Once identified, these factors must be reduced or controlled to an acceptable level and a value for the range of acceptable uncertainty assigned where possible (7).

Note: laboratories should therefore seek to explain their process of ‘consideration of uncertainty’ in terms which technical assessors will understand. It is likely that unless the uncertainty of measurement is expressed in statistical terms, appropriate ‘consideration’ will lead to a conclusion that there are too many variables in the process to express the uncertainty in a meaningful way.

Safety considerations

Specimen collection, transport and storage

For specimen collection, transport and storage you should:

• use aseptic technique

• collect specimens in appropriate CE marked leak proof containers and transport in sealed plastic bags (1) (2)

• collect swabs into appropriate transport medium and transported in sealed plastic bags

Adhere to compliance with postal, transport and storage regulations is essential.

For more information on specimen transport, refer to UK SMI U 1: National user manual template.

The above guidance should be supplemented with local COSHH and risk assessments.

Specimen processing

Any laboratory procedures that give rise to infectious aerosols must be conducted in a microbiological safety cabinet (3).

As a minimum, it is recommended that the processing of any culture that may result in generation of aerosols should be processed in a microbiological safety cabinet in accordance with the relevant risk assessment, ACDP and HSE guidelines (3).

Processing of diagnostic sample cultures that are assessed to be at higher risk of containing hazard group 3 organisms must be undertaken under appropriate containment conditions as determined by risk assessment, and as required by Biological agents: managing the risks in laboratories and healthcare premises (3). This will normally be under full CL3 conditions. Such organisms include Mycobacterium species, Brucella species, Bacillus anthracis, Blastomyces dermatitidis, Histoplasma capsulatum, Coccidiodes immitis.

Refer to current guidance on the safe handling of all organisms discussed in each UK SMI. The above guidance should be supplemented with local COSHH and risk assessments.

Notification to UKHSA or equivalent in the devolved administrations

The Health Protection (Notification) regulations 2010 require diagnostic laboratories to notify the UK Health Security Agency (UKHSA) when they identify the causative agents that are listed in Schedule 2 of the regulations (4) (5). Notifications must be provided in writing, on paper or electronically, within 7 days. Urgent cases should be notified orally and as soon as possible, recommended within 24 hours. These should be followed up by written notification within 7 days.

For the purposes of the Notification Regulations, the recipient of laboratory notifications is the local UKHSA health protection team. If a case has already been notified by a registered medical practitioner, the diagnostic laboratory is still required to notify the case if they identify any evidence of an infection caused by a notifiable causative agent.

Notification under the Health Protection (Notification) Regulations 2010 does not replace voluntary reporting to UKHSA. The vast majority of NHS laboratories voluntarily report a wide range of laboratory diagnoses of causative agents to UKHSA and many UKHSA health protection teams have agreements with local laboratories for urgent reporting of some infections. This should continue.

Note: The Health Protection Legislation Guidance (2010) includes reporting of Human Immunodeficiency Virus (HIV) and Sexually Transmitted Infections (STIs), Healthcare Associated Infections (HCAIs) and Creutzfeldt–Jakob disease (CJD) under ‘Notification Duties of Registered Medical Practitioners’: it is not noted under ‘Notification Duties of Diagnostic Laboratories’.

Other arrangements exist in Scotland (6), Wales (8) and Northern Ireland (9).

Reference grading information

SIGN reference grading used by UK SMIs when assessing references

References used in the UK SMIs are assessed using the Scottish Intercollegiate Guidelines Network (SIGN) approach. UK SMI documents commencing review from August 2020 onwards will use SIGN. The tables below are a guide to what the grades indicate.

Grade	Power of study
1	Meta-analysis, systematic review, randomised controlled trial
2	Non-randomised controlled trial, cohort studies, case-control studies, cross-sectional studies, prevalence studies
3	Case reports/case series, consensus reports, descriptive studies, uncontrolled trials
No number	Not applicable

 

Grade	Quality of study
++	Document has appropriate presentation, is relevant to the topic, lacks bias, has a suitable method, originates from a good source and contains timely, up to date information.
+	Document is relevant to the topic but may have minor issues that impact the quality
-	Document is relevant to the topic but may have one or more serious issues that impact the quality

Modified GRADE table previously used by UK SMIs when assessing references

Prior to August 2020, references used in UK SMIs commencing review were assessed using a modified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Under this scheme, each reference is assessed and allocated a grade for strength of recommendation (A to D) and quality of the underlying evidence (I to VIII). A summary table that defines the grade is listed below:

Quality/certainty of evidence	Types of evidence
A Strongly recommended	I Evidence from randomised controlled trials, meta analysis and systematic reviews
B Recommended but other alternatives may be acceptable	II Evidence from non randomised studies
C Weakly recommended: seek alternatives	III Evidence from documents describing techniques, methods or protocols
D Never recommended	IV Non-analytical studies, for example, case reports, reviews, case series
	V Expert opinion and wide acceptance as good practice but with no study evidence
	VI Required by legislation, code of practice or national standard/guideline
	VII Letter/short communication/editorials/conference communication
	VIII Electronic citation

References

1. European Parliament. UK Standards for Microbiology Investigations (UK SMIs) use the term ‘CE marked leak proof container’ to describe containers bearing the CE mark used for the collection and transport of clinical specimens. The requirements for specimen containers are given in the EU in vitro Diagnostic Medical Devices Directive (98/79/EC Annex 1 B 2.1) which states: ‘The design must allow easy handling and, where necessary, reduce as far as possible contamination of, and leakage from, the device during use and, in the case of specimen receptacles, the risk of contamination of the specimen. The manufacturing processes must be appropriate for these purposes’. 1998. ++
    
2. Official Journal of the European Communities. Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitro diagnostic medical devices 1998. 1 to 37. ++
    
3. Advisory Committee on Dangerous Pathogens. Management and operation of microbiological containment laboratories. Health and Safety Executive 2019. ++
    
4. UK Health Security Agency (UKHSA). Laboratory reporting to UKHSA: A guide for diagnostic laboratories. 2023. ++
    
5. Department of Health. Health Protection Legislation (England) Guidance. 1 to 112. 2010. ++
    
6. Scottish Government. Public Health (Scotland) Act. 2008. ++
    
7. ISO/TS 20914:2019 Medical laboratories – Practical guidance for the estimation of measurement uncertainty, 2019 ++
    
8. The Welsh Assembly Government. Health Protection Legislation (Wales) Guidance. 2010. ++
    
9. Home Office. Public Health Act (Northern Ireland) 1967 Chapter 36. 1967. ++