3 Approach to evidence generation

3.1 Evidence gaps and ongoing studies

There are no ongoing or planned studies that evaluate the diagnostic accuracy of these technologies in primary care. The ENDOBEST study (NCT06794424), ADOmiRNA study and a planned NHS pilot study may address some of the gaps for Endotest around resource use, subgroup analyses in young people and diagnostic accuracy by the end of 2027. But these studies are all in secondary care. Some diagnostic accuracy and laparoscopy rate data may be provided for EndoSure by the ADDEND study (ISRCTN83220665) and a planned NHS pilot.

Table 1 summarises the evidence gaps and ongoing studies that might address them. Information about evidence status is derived from the external assessment group's report; evidence not meeting the scope and inclusion criteria is not included. The table shows the evidence available to the committee when the guidance was published.

**Table 1 Evidence gaps and ongoing studies**
Evidence gap	EndoSure	Endotest
Diagnostic accuracy in NHS primary care setting	No evidence	No evidence
Impact on diagnostic pathway and resource use	No evidence	No evidence Ongoing study
Patient outcomes and experience	Limited evidence	Limited evidence Ongoing study
Clinical effectiveness in different subgroups	No evidence Ongoing study	No evidence Ongoing study

3.2 Data sources

No existing data registries or audits were identified as potential sources of real-world data that may address the evidence gaps. Some existing data sources, such as the NHS England Secure Data Environment (SDE) service and Hospital Episode Statistics (HES), could support evidence generation by providing long-term outcomes if they are linked to primary data collection. NICE's real-world evidence framework provides detailed guidance on assessing the suitability of a real-world data source to answer a specific research question.

3.3 Evidence collection plan

The suggested approach to addressing the evidence gaps for the technologies is a cross-sectional diagnostic accuracy study and a real-world comparative cohort study.

Cross-sectional diagnostic accuracy study

A cross-sectional diagnostic accuracy study would assess the accuracy of the technology against a reference standard (MRI). Reported accuracy should include sensitivity, specificity, and negative and positive predictive values.

The committee noted that the gold standard for these tests is laparoscopy. But it would be unethical to use this when there is a negative test result to confirm true negativity. Given the lengthy waiting list for laparoscopy for diagnosis and treatment, the committee discussed that using laparoscopy for evidence-generation purposes would not be an appropriate or ethical use of NHS resources. The committee agreed that using MRI would be an appropriate reference standard instead. It also heard that access to MRI may be limited. Latent class analyses or other statistical analyses may be appropriate when a gold standard is unsuitable, if multiple test results (and clinical history data) are readily available.

Real-world comparative cohort study

This approach would follow an intervention arm and a control arm and compare their outcomes. This design would allow the clinical impact of the technologies and the resource use associated with their implementation in primary care to be assessed. Qualitative data could be generated through appropriate methods like surveys, focus groups or interviews, as highlighted in NICE's real-world evidence framework. This could include reported outcomes (acceptability, usability and preferences) from people using the service.

Despite consistent eligibility criteria, non-random assignment to interventions can lead to confounding bias, complicating interpretation of the treatment effect. So, approaches should be used that balance confounding factors across comparison groups, for example using propensity score methods. To achieve this robustly, data collection will need to include prognostic factors related to both the intervention delivered and patient outcomes. These should be defined with input from clinical specialists. Incomplete records and demographically imbalanced groups can lead to bias if they are unaccounted for.

Data collection should follow a predefined protocol. Quality assurance processes should be put in place to ensure the integrity and consistency of data collection. NICE's real-world evidence framework provides guidance on planning, doing and reporting real-world evidence studies. It also provides best-practice principles for a robust design of real-world evidence when assessing comparative treatment effects using a prospective cohort study design.

3.4 Data to be collected

Diagnostic accuracy study

Patient characteristics, including age, ethnicity, menopausal status and conditions that may complicate imaging
Diagnostic accuracy, including sensitivity, specificity, and positive and negative predictive values
Prevalence of disease
Multiple pathology rate
Test failure rate
Adverse events

Real-world comparative cohort study

Patient characteristics as above for diagnostic study
Details of the technology
Health-related quality-of-life data (baseline and after the intervention), including symptom reduction, ideally collected using the EQ-5D-3L questionnaire
Detail of the technology (software name, version and configuration settings)
Image details (including anatomical location, projection when considering X-rays and manufacturer of CT or X-ray machine)
Time from symptom onset to referral, presumptive diagnosis and definitive diagnosis
Time from presentation in primary care to referral, presumptive diagnosis and definitive diagnosis
Diagnostic laparoscopy rate
rASRM (revised American Society for Reproductive Medicine) rating, where laparoscopy is available
Time to treatment
Results of any additional downstream tests
Number of primary-care consultations
Number of referrals and referral requests
Number of hospital appointments and emergency department visits
Health-related quality-of-life data (ideally EQ-5D-5L and Endometriosis Health Profile-30 questionnaire, and including anxiety)
Imaging details
Multiple pathology rate
Adverse events
Test failure rates
Patient-related experience measures, ideally intervention uptake, satisfaction, acceptability and preferences
Costs associated with the technologies, including acquisitions, implementation (for example, cost of staffing, an additional room, training and transportation of samples) and additional downstream testing.

3.5 Evidence generation period

This will be 3 years to allow for setting up, implementing the test, data collection, analysis and reporting.

3.6 Following best practice in study methodology

Following best practice in conducting studies is paramount to ensuring the reliability and validity of the research findings. Adherence to rigorous guidelines and established standards is crucial for generating credible evidence that can ultimately improve patient care. The NICE real-world evidence framework details some key considerations.

Within the context of an early-use assessment a key factor to consider as part of the informed consent process is to ensure that patients (and their carers, as appropriate) understand that data will be collected to address the evidence gaps identified in section 2. Where applicable this should take account of NICE guidance about shared decision making.

How are you taking part in this consultation?

Question on Document

Question on Document

Evidence generation plan for HTG10877 Technologies for diagnosing endometriosis in primary care