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Liquid-based cytology: NICE technology appraisal process

The guidance on liquid-based cytology (LBC) for cervical screening was a part of the technology appraisals work programme. Appraisals are independent considerations of the clinical and cost-effectiveness of health technologies. Topics include medicines, medical devices, diagnostic techniques, surgical procedures and health promotion activities.
NICE follows an open and transparent process for its appraisals (see Figure 1) and is advised by an independent appraisal committee. Members of the committee are drawn from the NHS, healthcare professionals, patients and carers, and academia.

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Once a technology has been referred to NICE for appraisal, an independent academic centre is commissioned, through NHS Research and Development, to prepare a systematic review of both the published evidence and data submitted by manufacturers. This review is referred to as the Assessment Report. Stakeholder organisations that will be involved in the appraisal are then identified and consulted with. Stakeholders include patient/carer organisations, healthcare professional bodies, and manufacturers related to the technology and the condition for which it is indicated.
Stakeholders are invited to prepare submissions to inform the appraisal, and the professional and patient groups nominate experts. All the submissions, the Assessment Report and any comments on it are combined to form an Evaluation Report, which is sent to the appraisal committee. The appraisal committee then meets to consider this report alongside evidence from the expert witnesses nominated by the patients and professionals.
On average each appraisal takes around 12 months to complete. The appraisal process includes periods of consultation with stakeholders. These groups also have the right to appeal against the final guidance before it is issued to the NHS, should they wish to do so.
When NICE was established in April 1999, it recognised that the processes it established would evolve. Therefore, as expected, there have been a number of changes to the appraisal process that was used to appraise LBC for cervical screening. For example, although NICE originally wanted to publish consultation and appeal documents on its website, early appraisals, including the appraisal of LBC, remained confidential until the final guidance was published. This confidentiality was introduced at the request of the healthcare industries (through their representative groups, the ABPI and the ABHI), who suggested publishing provisional decisions might be in breach of stockmarket regulations and create unnecessary anxiety for patients. Following widespread consultation, NICE reversed this decision as one of the changes which resulted in the current process that was published in February 2001.

The appraisal of LBC for cervical screening
There are about 3,000 new cases of cervical cancer diagnosed each year in England and Wales, leading to about 1,200 deaths. The number of deaths from cervical cancer has been decreasing over the last 20 years, due in part to the introduction of the NHS Cervical Screening Programme in 1987.
The current screening programme is based on the Pap smear test, where cells are collected from the cervix using a disposable spatula. The sample collected is spread onto a glass slide and sprayed with, or dipped in, a liquid to fix the sample onto the slide. It is then sent to a hospital laboratory, where it is stained and ­examined by a cytologist.
There are problems associated with the Pap smear technique itself, related to both sampling errors during acquisition of the smear and the laboratory methodology used to evaluate the cytological specimens produced. Thus the sensitivity (avoidance of false-negative results) and specificity (avoidance of false-positive results) of the technique are variable and not considered optimal at the present time. There are relatively high levels of "inadequate" test results that are unsuitable for reporting due to: variable sampling of appropriate cells from the cervix; poor transfer of the cellular material onto the glass slide; suboptimal preparation and fixation by the smear taker; and, to a lesser extent, variability in microscopic assessment in the laboratory. In addition, significant numbers of Pap smears are reported as cytologically "borderline" or "mildly abnormal", leading, under current screening policy, to a reduced screening interval and possibly additional examinations, such as colposcopy and biopsy. Repeat screening and additional tests cause distress and inconvenience to the women involved and have significant cost implications.
LBC techniques, which are established practice in other cytology screening areas, offer a new way to prepare the smear sample for examination. The sample is collected in a similar fashion to the standard Pap smear using a special spatula device, or "broom-like" device, to brush cells from the neck of the cervix. The head of the spatula where the cells are lodged is then broken off into a small tube containing preservative fluid, or, alternatively, the cells are rinsed directly into the preservative fluid. This sample is then sent to the laboratory, where it is mixed and treated to remove unwanted material. A thin layer of the resulting cell suspension is deposited onto a slide and stained. The slide is then examined in the usual way.
The principal criteria for assessing the effectiveness of LBC compared with conventional Pap smear testing are the test sensitivity and specificity and the numbers of smears that are considered inadequate for reporting. The definitions of smear inadequacy and histological staging vary internationally. The UK system differs from the more widely used Bethesda system. Thus, care is needed in assessing the implications for the UK of studies based on the Bethesda system. The ultimate criteria, however, for assessing the overall clinical effectiveness of the screening programme will be its effects on the incidence of cervical cancer, morbidity and mortality of the disease, and the inconvenience and anxiety associated with screening.
NICE issued its guidance on LBC for cervical screening to the NHS in England and Wales in June 2000.(1) In summary, the guidance stated that:

  • Research evidence suggests that LBC could ­provide important benefits, but the quality of the evidence is variable and some areas of uncertainty remain.
  • Although there is insufficient evidence to justify the introduction of LBC technology across England and Wales at present, it is likely that LBC will lead to improvements in cervical screening.
  • Pilot projects should be undertaken that are designed to collect information on the effects, costs and practical implications of introducing LBC technology into the cervical screening programmes in England and Wales.
  • The Department of Health and the National Assembly for Wales have been asked to consider making arrangements for the regional pilot studies of LBC referred to in this guidance.

The full guidance and the assessment report are published on the NICE website.The pilot studies recommended in the guidance on LBC are now underway. They are being run by the NHS Cancer Screening Programme and are expected to report during 2002. Once the outcomes of the pilot studies are available, NICE will review its guidance.

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Reference
1. NICE. Guidance on the use of liquid-based cytology for cervical ­screening. NICE Technology Appraisal Guidance No. 5. London: National Institute for Clinical Excellence; 2000. Available from URL: http:// www.nice.org.uk

For more ­information on liquid-based ­cytology see "Liquid-based ­cytology versus conventional smears" by C Mary Anderson, p. 69.