This information collection is a core HTA, i.e. an extensive analysis of one or more health technologies using all nine domains of the HTA Core Model. The core HTA is intended to be used as an information base for local (e.g. national or regional) HTAs.
Fecal Immunochemical Test (FIT) for colorectal cancer screening compared to CRC screening with Guaiac –based fecal occult blood test (gFOBT) in the screening of Adenomas, as non-malignant precursor lesions of ColoRectal Cancer (CRC). in healthy and/or asymptomatic adults and elderly Any adult over 50 years old, both men and women, with average risk of CRC.
(See detailed scope below)
Authors: Gottfried Endel
A comparison of tests with identical test characteristic, similar accuracy and identical types of consequences pose no specific ethical problems. If a regional health care system has already decided to implement a population based screening for colorectal cancer the main ethical issues are already decided. A choice of the screening test for occult blood in faeces is very similar to the decision which product to choose, if there are different vendors.
The variability of ICERs in ECO5 shows that the tests are really very similar. They both dominate no screening but the indirect comparison of the two tests varies considerably. Even so most models attribute dominance to FIT some are favorable for gFOBT. To address these uncertainties an appraisal of the HTA information with application of regional values and experiences has to be done. There the usual framework for decisions in the respective health care system can be applied. This should also cover the question of opportunity cost if the decision imposes a financial impact on the sytem.
Questions addressing (population) screening activities need a special approach in ethical analysis. There are the following points with a framework different from usual treatment interventions:
There is also no information in medical literature about the basics of a health care system. The challenge in a core HTA is to be specific on an European level but according to the organization of health care in the member states only to outline the questions and principles addressed so they can be applied on the local level.
In the case of the comparison of Fecal Immunochemical Test (FIT) for detection of occult blood in the stool associated with colorectal lesions (adenomas and colorectal cancer-CRC), under conditions of population based colorectal cancer screening, comparing with CRC screening with Guaiac –based fecal occult blood test (gFOBT) only the questions of the effectiveness and safety of the test in combination with the economic consequences are of interest. These questions are covered in the corresponding domains.
The collection scope is used in this domain.
|Technology||Fecal Immunochemical Test (FIT) for colorectal cancer screening
FITs use an antibody (immunoglobulin) specific to human globin, the protein component of haemoglobin, to detect fecal occult blood. Immunochemical tests have improved test characteristics compared to conventional guaiac-based tests for fecal occult blood. FIT should not be subject to interference from dietary blood and it is more specific to bleeding from the distal gastrointestinal tract. They could be analytically and clinically more sensitive and specific, Their measurement can be automated and the user can adjust the concentration at which a positive result is reported. A wide range of qualitative and quantitative tests is presently available, with varying levels of sensitivity and specificity (like Hem-SP/MagStream H, Fujirebio Inc. Japan ; OC-Sensor, Eiken Chemical Co., Tokyo, Japan; FOB Gold, Medinostics Products Supplier; Sentinel Diagnostics SpA, Milan, Italy).
|Intended use of the technology||Screening |
CRC screening with faecal inmunochemical test (FIT) for detection of occult blood in the stool associated with colorectal lesions (adenomas and CRC).
The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Early detection and treatment of colorectal lesions before they become symptomatic has the potential to improve control of the disease, reducing morbidity and mortality associated to CRC. Early treatment of invasive lesions can be generally less detrimental for quality of life. The endoscopic removal of pre-malignant lesions also reduces the incidence of CRC by stopping the progression to cancer. Colorectal cancers and adenomatous polyps bleed has providing fecal blood haemoglobin as the biomarker of choice for current screening programmes. Stool samples could be periodically taken and analyzed for the presence of occult blood, as an early sign of colorectal lesions (adenoma or CRC).
Target conditionAdenomas, as non-malignant precursor lesions of ColoRectal Cancer (CRC).
Target condition description
CRC is the third most common in incidence and the fourth most common cause of cancer death worldwide. CRC is particularly suitable for screening. The disease is believed to develop in a vast majority of cases from non-malignant precursor lesions called adenomas. Adenomas can occur anywhere in the colorectum after a series of mutations that cause neoplasia of the epithelium. At some time , the adenoma may invade the submucosa and become malignant. Initially, this malignant cancer is not diagnosed and does not give symptoms (preclinical phase). It can progress from localised (stage I) to metastasised (stage IV) cancer, until it causes symptoms and is diagnosed. Only 5–6% of the population actually develop CRC. The average duration of the development of an adenoma to CRC is estimated to be at least 10 years. This long latent phase provides a window of opportunity for early detection of the disease.
Target population sex: Any. Target population age: adults and elderly. Target population group: Healthy and/or asymptomatic people.
Target population description
Adults, average risk of CRC, aged 50 years or over.
The best age range for offering gFOBT or FIT screening has not been investigated in trials. Circumstantial evidence suggests that mortality reduction from gFOBT is similar in different age ranges between 45 and 80 years .The age range for a national screening programme should at least include people aged 60 to 64 years in which CRC incidence and mortality are high and life-expectancy is still considerable. Only the FOBT for men and women aged 50–74 years has been recommended todate by the EU (Council Recommendation and the European guidelines for quality assurance in CRC screening and diagnosis).
Members of families with hereditary syndromes, previous diagnosis of CRC or pre-malignant lesions should follow specific surveillance protocols and are not included in the target population
|Comparison||CRC screening with Guaiac –based fecal occult blood test (gFOBT)
CRC screening with Guaiac–based fecal occult blood test (gFOBT)
The guaiac-based FOBT is still a commonly used method for detecting blood in faeces. To detect hemoglobin the test uses guaiac gum and its efficacy as a colorectal cancer screening test has been analyzed in several randomised controlled trials. The test detects the haem component of haemoglobin, which is identical across human and animal species and is chemically robust and only partially degraded during its passage through the gastrointestinal tract. gFOBTs cannot distinguish between human blood and blood residues from the diet.
Many guaiac-based tests are currently on the market (like Coloscreen, Helena Laboratories,Texas,USA; Hema-screen Immunostics Inc.; Hemoccult, Beckman Coulter Inc.; Hemoccult SENSA, Beckman Coulter Inc.; MonoHaem, Chemicon Europe Ltd; Hema-Check, Siemens PLC; HemaWipe, Medtek Diagnostics LLC)
The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Population-based programmes have been rolled out nationwide in several European countries. Many member states haveestablished nationwide non-population-based programmes. Some states are planning or piloting a nationwide population-based programme. These have adopted only FOBT, some only FIT, some a mix between FOBT and endoscopy, or only colonoscopy.
CUR and TEC
|Topic||Issue||Relevant||Research questions or rationale for irrelevance|
|F0001||Principal questions about the ethical aspects of technology||Is the technology a new, innovative mode of care, an add-on to or modification of a standard mode of care or a replacement of a standard?||yes||Is FIT a new, innovative mode of care, an add-on to or modification of a standard mode of care or a replacement of a standard?|
|F0002||Principal questions about the ethical aspects of technology||Can the technology challenge religious, cultural or moral convictions or beliefs of some groups or change current social arrangements?||no||This would only be relevant between organized and opportunistic screening. But it's no question between two tests.|
|F0003||Principal questions about the ethical aspects of technology||What can be the hidden or unintended consequences of the technology and its applications for different stakeholders.||no||This would only be relevant between organized and opportunistic screening. But it's no question between two tests.|
|F0006||Autonomy||Can the technology entail special challenges/risk that the patient/person needs to be informed of?||yes||Can FIT entail special challenges/risk that the patient/person needs to be informed of?|
|F0004||Autonomy||Does the implementation or use of the technology challenge patient autonomy?||no||This would only be relevant between organized and opportunistic screening. But it's no question between two tests.|
|F0005||Autonomy||Is the technology used for patients/people that are especially vulnerable?||no|
|F0007||Autonomy||Does the implementation challenge or change professional values, ethics or traditional roles?||no|
|F0010||Beneficence/nonmaleficence||What are the benefits and harms for patients, and what is the balance between the benefits and harms when implementing and when not implementing the technology? Who will balance the risks and benefits in practice and how?||yes||What are the benefits and harms for patients, and what is the balance between the benefits and harms when implementing and when not implementing FIT? Who will balance the risks and benefits in practice and how?|
|F0011||Beneficence/nonmaleficence||Can the technology harm any other stakeholders? What are the potential benefits and harms for other stakeholders, what is the balance between them? Who will balance the risks and benefits in practice and how?||no|
|F0012||Justice and Equity||What are the consequences of implementing / not implementing the technology on justice in the health care system? Are principles of fairness, justness and solidarity respected?||yes||What are the consequences of implementing / not implementing FIT on justice in the health care system? Are principles of fairness, justness and solidarity respected?|
|F0013||Justice and Equity||How are technologies presenting with relevantly similar (ethical) problems treated in health care system?||yes||How are technologies presenting with relevantly similar (ethical) problems treated in health care system?|
|F0017||Questions about effectiveness and accuracy||What are the proper end-points for assessment and how should they be investigated?||yes||What are the proper end-points for assessment and how should they be investigated?|
|F0018||Questions about effectiveness and accuracy||Are the accuracy measures decided and balanced on a transparent and acceptable way?||yes||Are the accuracy measures decided and balanced on a transparent and acceptable way?|
|F0008||Human Dignity||Does the implementation or use of the technology affect human dignity?||no|
|F0009||Human integrity||Does the implementation or use of the technology affect human integrity?||no||This would only be relevant between organized and opportunistic screening. But it's no question between two tests which are equivalent in this respect.|
|F0014||Rights||Does the implementation or use of the technology affect the realisation of basic human rights?||no|
|F0016||Legislation||Is legislation and regulation to use the technology fair and adequate?||no|
The project scope is applied in this domain. The ethical dimension of questions already covered in other domains adds only minor extensions to the findings there.
The discussion of ethical issues is based on the results of the other domains and addresses in a discursive manner of coherence analysis (CA) according to the methodological recommendations for these domain aspects which were already covered but not scrutinized with regards to ethical aspects included. This methodological approach is chosen to minimize overlap and to take into account the potential of regional differences in values and opinions regarding potential marginal differences for ongoing programs.
Nevertheless a literature search was performed to find ethical discussions comparing these two tests or comparing two very similar tests in general. The search in pubmed and google sholar produced no literature addressing these issues. Articles on ethical issues for the questions of
were identified. Also a framework for ethical questions in public health referred to some common questions of screening but did not expand the comprehensive methodological guidance available for the core model.
Quality assessment tools or criteria
As the goal on the level of the core HTA is to define the framework for the ethical analysis only criteria for the application of this framework will be defined. The quality assessment than can be done by using these criteria in the local scope. There the specific answer to the questions of the element cards have to be found by gathering the local information necessary.
As mentioned as method CA was chosen. The main idea of CA is to reflect upon the consistency of ethical argumentations or broader theories on different levels, without prescribing which facts, arguments or principles are prima facie relevant. It is a procedural, pragmatic approach, i.e. describes a procedure of approaching moral issues without claims of providing direct answers on “right or wrong”. This supports regional adaptation by focusing discussions on the value given special criteria in the specific context of the own health care system.
The criteria to consider coming from the effectiveness domain are:
The criteria to consider coming from the safety domain are:
The criteria to consider coming from the economic domain are:
Analysis and synthesis
The main sources for the ethical analysis are the results of the other domains. As shown in the EUNetHTA member survey of the domain on current use of the technologies CRC screening programs are widely ongoing in Europe. So the discussion of isolated aspects will be provided and no attempt is done to produce a synthesis fitting all different regional conditions and frameworks. The isolated aspects may – if appropriate – support the local adaptation of the assessment.
The comparison of two tests to detect occult blood in faeces poses no serious ethical problems. The main issues regarding screening arise in the field of autonomy of the individual – which should be taken care of with objective information -, the measurement of benefits and harms – as done in the domains of EFF and SAF – and justice – this is addressed mostly in the ECO domain.
As the characteristics of the tests, their consequences and the informational content in a population based screening are structural identical ethical considerations for the marginal differences are not necessary. The information documented in the other domains suffices to support an appraisal process on the regional level. This appraisal to apply the framework of the regional values used in a specific health care system may address uncertainties which remain although with this collection of HTA information at hand.<< Costs and economic evaluationOrganisational aspects >>