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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 ) versus guaiac-based fecal occult blood test (FOBT) for colorectal cancer screening

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)

HTA Core Model Application for Screening Technologies 1.0
Core HTA
Published
Tom Jefferson (Agenas - Italy), Marina Cerbo (Agenas - Italy), Nicola Vicari (Agenas - Italy)
Mirjana Huic (AAZ), Agnes Männik (UTA - Estonia), Jesus Gonzalez (ISCIII - Spain), Ingrid Rosian (GÖG - Austria), Gottfried Endel (HVB - Austria), Valentina Rupel (IER - Slovenia), Alessandra Lo Scalzo (Agenas - Italy), Ingrid Wilbacher (HVB - Austria)
Agenas - Agenzia nazionale per i servizi sanitari regionali
AAZ (Croatia), AETSA (Spain), A. Gemelli (Italy), Avalia-t (Spain), CEIS (Italy), CEM (Luxembourg), GÖG (Austria), HAS (France), HVB (Austria), IER (Slovenia), ISCIII (Spain), Laziosanità (Italy), NCPHA (Bulgaria), NIPH (Slovenia), NSPH (Greece), NSPH MD (Romania), Osteba (Spain), Regione Veneto (Italy), SBU (Sweden), SNHTA (Switzerland), THL (Finland), UTA (Estonia).
5.4.2013 13.07.00
31.7.2014 9.21.00
Jefferson T, Cerbo M, Vicari N [eds.]. Fecal Immunochemical Test (FIT ) versus guaiac-based fecal occult blood test (FOBT) for colorectal cancer screening [Core HTA], Agenas - Agenzia nazionale per i servizi sanitari regionali; 2014. [cited 2 October 2022]. Available from: http://corehta.info/ViewCover.aspx?id=206

Fecal Immunochemical Test (FIT ) versus guaiac-based fecal occult blood test (FOBT) for colorectal cancer screening

<< Description and technical characteristics of technologyClinical Effectiveness >>

Safety

Authors: Agnes Männik, Irena Guzina, Petra Jandova, Leonor Varela Lema, Gerardo Atienza Merino

Summary

FIT and gFOBT are non-invasive tests and therefore no direct harms are expected. Indirect harms can be caused by a wrong or delayed diagnosis or by harms related to subsequent colonoscopy. Eventually, psychological impact of the screening (including psychological consequences of false-positive and false-negative test results) and patient discomfort related to the procedures must be considered.The overall number of adverse events depends on sensitivity and specificity of the  screening tests.

Subsequent colonoscopies may cause following complications – perforations of the colon, bleeding, infections, pain and discomfort. The false-positive test results may cause anxiety and distress, overdiagnosis and overtreatment. The false-negative test results may delay the detection of illness and the start of treatment.

The onset of harms (both psychological and from subsequent colonoscopies) may be immediate or delayed.

There is no evidence that there are susceptible patient groups that are more likely to be harmed through use of FIT. However, patients with comorbidities can be under higher risk with follow-up colonoscopy.

There are some organisational factors, which can affect the harms. The false-positive test results from gFOBT can be reduced by following dietary and medication restrictions. The FIT samples should be kept in refridgerator and cooling bags should be used when sending samples to clinic.

The risk of false-positive and false-negative test results might be increased if the laboratory personnel is unexperienced (risks of inaccurate interpretation of results). Complications from colonoscopy also may depend on the education and experience of health professional.

Introduction

The safety domain describes unwanted or harmful effects from FIT and gFOBT. As colonoscopy is directly connected to FIT and gFOBT, the unwanted effects from colonoscopy are also described. Indirect harms specific to colorectal cancer screening in vitro are false-positive and false-negative test results, which may cause anxiety and stress, and lead to unnecessary further investigations (eg colonoscopy, which can cause harm in turn) or may cause delay in detection of the illness. 

Methodology

Frame

A modified collection scope is used in this domain.

TechnologyFecal Immunochemical Test (FIT) for colorectal cancer screening
Description (modified from collection scope)

In CRC screening colonoscopy, that is invasive procedure, is used after positive FIT or gFOBT for approving or disapproving the occult blood test result. In that context colonoscopy is directly connected with using FIT or gFOBT and the harms related with colonoscopy are included in the analysis.

Intended use of the technology (modified from collection scope)Screening

Colonoscopy is considered as gold standard for detecting lesions and colorectal cancer.

Target condition
Adenomas, 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

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

ComparisonCRC screening with Guaiac –based fecal occult blood test (gFOBT)
Description (modified from collection scope)

The psychological harms from false-positive or false-negative test results are most likely not different using FIT or gFOBT. Thus psychological harms are described without comparison.

While gold standard for approving FIT or gFOBT results is colonoscopy, number of other diagnostic methods are available and are considered as comparisons if relevant. The alternative methods are - flexible sigmoidoscopy, computer tomography (CT), barium enema.

Outcomes

CUR and TEC

  • Health problems (target condition)
  • Epidemiology
  • Burden of disease
  • Target population
  • Current management of the condition
  • Features of the technology
  • Life-Cycle
  • Regulatory status
  • Utilization
  • Investments and tools required to use the technology
  • Training and information needed to use the technology

SAF

  • Colonoscopy probability of perforation
  • Colonoscopy with polypectomy probability of perforation
  • Colonoscopy probability of death following perforation
  • Probability of bleeding following colonoscopy
  • Psychological harms from false-negatives and false-positives (and generally from participating in screening program)

EFF

  • Test (FIT and gFOBT) sensitivity for adenomas
  • Test (FIT and gFOBT) sensitivity for cancer
  • Test (FIT and gFOBT) specificity for adenomas
  • Test (FIT and gFOBT) specificity for cancer 
  • Adenoma incidence (detection rates)
  • Rectal cancer incidence (detection rates)
  • Colon cancer incidence (detection rates)
  • CRC incidence (detection rates)
  • Stage distribution of detected cancers
  • Rectal cancer specific mortality
  • CRC specific mortality
  • Overall mortality
  • Life years saved

ECO:

  • Model/template for  national pilots  to assess the costs and benefits of the two alternative  technologies FIT and gFOBT  and also no-programmed-screening
  • Systematic literature search of   available models and/or economic  evaluation for screening colorectal cancer with FIT and gFOBT and no screening programme
  • Resource Utilization: Publicly funded health care payer costs (screening tests, further examinations e.g. labor, colonoscopy  and treatments and administration and organisation costs of screening programme) for FIT and gFOBT (in cooperation with ORG)
  • Cost per Case detected (average, marginal, incremental) =  intermediate outcome – optional, not decided yet (relevant for deciding how often a test should be carried out and what are the incremental costs for a “new” detected case
  • Indirect Costs: not for the Core modell (should be decided later on)
  • Test accuracy: from SAF
  • Cost effectiveness analysis: HRQoL measures (both generic and context specific) (EFF and SAF for help, own Lit.research), ICER

 ORG:

  • Responsiveness of target population to invitation
  • Invitation-reminder system
  • Competence of human resources – health professionals
  • Investments needed (material,equipment)
  • Costs of using both tests (FIT, gFOBT)
  • Timeliness of results and future phases
  • Use of tools for process monitoring (completed check lists)
  • Model for Budget Impact Analysis from perspective of the payer

SOC

  • Compliance with the tests (FIT, gFOBT)
  • Anxiety and any psychological effects of using  one test or another
  • Information, counseling, communication (quality of) for the use of tests
  • Satisfaction  
  • Quality of life
  • Equity of access

LEG

  • Information as baseline for an informed consent
  • Harms or inequities that can be taken to court

Assessment elements

TopicIssue RelevantResearch questions or rationale for irrelevance
C0001Patient safetyWhat kind of harms can use of the technology cause to the patient; what are the incidence, severity and duration of harms?yesWhat kind of harms can use of FIT cause to the patient; what are the incidence, severity and duration of harms?
C0002Patient safetyWhat is the dose relatedness of the harms to patients?yesWhat is the dose relatedness of the harms to patients?
C0003Patient safetyWhat is the timing of onset of harms to patients: immediate, early or late?yesWhat is the timing of onset of harms to patients: immediate, early or late?
C0004Patient safetyIs the incidence of the harms to patients likely to change over time?yesIs the incidence of the harms to patients likely to change over time?
C0005Patient safetyAre there susceptible patient groups that are more likely to be harmed through use of the technology?yesAre there susceptible patient groups that are more likely to be harmed through use of FIT?
C0006Patient safetyWhat are the consequences of false positive, false negative and incidental findings brought about using the technology to the patients from the viewpoint of patient safety?yesWhat are the consequences of false positive, false negative and incidental findings brought about using FIT to the patients from the viewpoint of patient safety?
C0007Patient safetyWhat are the special features in using (applying/interpreting/maintaining) the technology that may increase the risk of harmful events?yesWhat are the special features in using (applying/interpreting/maintaining) FIT that may increase the risk of harmful events?
C0008Patient safetyWhat is the safety of the technology in comparison to alternative technologies used for the same purpose?yesWhat is the safety of FIT in comparison to alternative technologies used for the same purpose?
C0029Patient safetyDoes the existence of harms influence tolerability or acceptability of the technology?yesDoes the existence of harms influence tolerability or acceptability of FIT?
C0020Occupational safetyWhat kind of occupational harms can occur when using the technology?yesWhat kind of occupational harms can occur when using FIT?
C0040Environmental safetyWhat kind of risks for public and environment may occur when using the technology?yesWhat kind of risks for public and environment may occur when using FIT?
C0061Safety risk managementIs there evidence that harms increase or decrease in different organizational settings?yesIs there evidence that harms increase or decrease in different organizational settings?
C0062Safety risk managementHow can one reduce safety risks for patients (including technology-, user-, and patient-dependent aspects)?yesHow can one reduce safety risks for patients (including technology-, user-, and patient-dependent aspects)?
C0063Safety risk managementHow can one reduce safety risks for professionals (including technology-, user-, and patient-dependent aspects)?yesHow can one reduce safety risks for professionals (including technology-, user-, and patient-dependent aspects)?
C0060Safety risk managementHow does the safety profile of the technology vary between different generations, approved versions or products?noIrrelevant in the context of outcomes stated in project description (colonoscopy has probably not changed over the past years and psychological harms from false-positives and false-negatives are the same no matter what test is used)
C0064Safety risk managementHow can one reduce safety risks for environment (including technology-, user-, and patient-dependent aspects)?noWill be discussed already under Issue C0040

Methodology description

Technology description:

In CRC screening, colonoscopy, that is invasive procedure, is used independently or after positive FIT or gFOBT for confirming or rejecting the occult blood test result. In that context colonoscopy is directly connected with using FIT or gFOBT and the harms related with colonoscopy are included in the analysis.

Use of technology:

Colonoscopy is considered as gold standard for detecting colon lesions and colorectal cancer.

Comparison:

The psychological harms from false-positive or false-negative test results are most likely not different using FIT or gFOBT. Thus psychological harms are described together.

While gold standard for approving FIT or gFOBT results is colonoscopy, number of other screening methods are available and are considered as comparators if relevant. The alternative methods are - flexible sigmoidoscopy, video capsule, computer tomography (CT), barium enema imaging.

Information sources

The domain literature search was used as the main information source. Also the studies from HAS (Haute Autorité de Santé) reports dated 2008 {2} and 2013 {1} were used. Relevant Cochrane systematic reviews were used. Additional searches were done through the Internet engine Google, where guidelines, reports and some free articles/studies on Oxford journals, PubMed etc. were found.

Quality assessment tools or criteria

None.

Analysis and synthesis

Different information sources were used to answer domain questions.

Result cards

Patient safety

Result card for SAF1: "What kind of harms can use of FIT cause to the patient; what are the incidence, severity and duration of harms?"

View full card
SAF1: What kind of harms can use of FIT cause to the patient; what are the incidence, severity and duration of harms?
Method
Result
Comment

Importance: Critical

Transferability: Completely

Result card for SAF2: "What is the dose relatedness of the harms to patients?"

View full card
SAF2: What is the dose relatedness of the harms to patients?
Method
Frame
Result
Comment

Importance: Unspecified

Transferability: Unspecified

Result card for SAF3: "What is the timing of onset of harms to patients: immediate, early or late?"

View full card
SAF3: What is the timing of onset of harms to patients: immediate, early or late?
Method
Result
Comment

Importance: Important

Transferability: Completely

Result card for SAF4: "Is the incidence of the harms to patients likely to change over time?"

View full card
SAF4: Is the incidence of the harms to patients likely to change over time?
Method
Result
Comment

Importance: Important

Transferability: Partially

Result card for SAF5: "Are there susceptible patient groups that are more likely to be harmed through use of FIT?"

View full card
SAF5: Are there susceptible patient groups that are more likely to be harmed through use of FIT?
Method
Result
Comment

Importance: Critical

Transferability: Completely

Result card for SAF6: "What are the consequences of false positive, false negative and incidental findings brought about using FIT to the patients from the viewpoint of patient safety?"

View full card
SAF6: What are the consequences of false positive, false negative and incidental findings brought about using FIT to the patients from the viewpoint of patient safety?
Method
Result
Comment

Importance: Important

Transferability: Completely

Result card for SAF7: "What are the special features in using (applying/interpreting/maintaining) FIT that may increase the risk of harmful events?"

View full card
SAF7: What are the special features in using (applying/interpreting/maintaining) FIT that may increase the risk of harmful events?
Method
Result
Comment

Importance: Important

Transferability: Completely

Result card for SAF8: "What is the safety of FIT in comparison to alternative technologies used for the same purpose?"

View full card
SAF8: What is the safety of FIT in comparison to alternative technologies used for the same purpose?
Method
Result

Importance: Important

Transferability: Completely

Result card for SAF10: "Does the existence of harms influence tolerability or acceptability of FIT?"

View full card
SAF10: Does the existence of harms influence tolerability or acceptability of FIT?
Method
Result
Comment

Importance: Important

Transferability: Partially

Occupational safety

Result card for SAF9: "What kind of occupational harms can occur when using FIT?"

View full card
SAF9: What kind of occupational harms can occur when using FIT?
Method
Result

Importance: Important

Transferability: Completely

Environmental safety

Result card for SAF11: "What kind of risks for public and environment may occur when using FIT?"

View full card
SAF11: What kind of risks for public and environment may occur when using FIT?
Method
Result

Importance: Important

Transferability: Completely

Safety risk management

Result card for SAF12: "Is there evidence that harms increase or decrease in different organizational settings?"

View full card
SAF12: Is there evidence that harms increase or decrease in different organizational settings?
Method
Result

Importance: Important

Transferability: Completely

Result card for SAF13: "How can one reduce safety risks for patients (including technology-, user-, and patient-dependent aspects)?"

View full card
SAF13: How can one reduce safety risks for patients (including technology-, user-, and patient-dependent aspects)?
Method
Result

Importance: Important

Transferability: Completely

Result card for SAF14: "How can one reduce safety risks for professionals (including technology-, user-, and patient-dependent aspects)?"

View full card
SAF14: How can one reduce safety risks for professionals (including technology-, user-, and patient-dependent aspects)?
Method
Result

Importance: Optional

Transferability: Completely

Discussion

There are no direct harms caused by either gFOBT or FIT.

Indirect harms can be caused by a wrong or delayed diagnosis or by harms related to subsequent colonoscopy. The total number of adverse events depends on the specificity and sensitivity of the tests and therefore may be different between gFOBT and FIT.  

There was limited evidence on different safety issues. Besides, study differences  (different populations, different study designs, different approaches in calculating the % of complications) made the interpretation and synthesis of the results difficult. 

References

  1. HAS recommendation on colorectal screening and prevention 2013 http://www.has-sante.fr/portail/upload/docs/application/pdf/2013-08/referentieleps_format2clic_kc_colon-vfinale_2013-08-30_vf_mel_2013-08-30_12-18-6_653.pdf
  2. iIFOBT in the program of organized CRC screening in France, HAS 2008 http://www.has-sante.fr/portail/upload/docs/application/pdf/2008-12/rapport_-_place_des_tests_immunologiques_de_recherche_de_sang_occulte_dans_les_selles_ifobt.pdf
  3. Hewitson P, Glasziou P, Irwig L, Towler B, Watson E. Screening for colorectal cancer using the faecal occult blood test, Hemoccult. Cochrane Database Syst Rev 2007;1
  4. Medical Services Advisory Committee. Faecal occult blood testing for population health screening. Reference 18 Assessment Report ed. Canberra: MSAC [www.msac.gov.au]; 2004.
  5. Senore, C., et al. (2011). "Acceptability and side-effects of colonoscopy and sigmoidoscopy in a screening setting." J Med Screen 18(3): 128-134
  6. Quintero, E., et al. (2012). "Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening." N Engl J Med 366(8): 697-706.
  7. Guittet, L., et al. (2007). "Comparison of a guaiac based and an immunochemical faecal occult blood test in screening for colorectal cancer in a general average risk population." Gut 56(2): 210-214.
  8. NHS Centre for Reviews and Dissemination. Diagnostic accuracy and cost-effectiveness of faecal occult blood tests used in screening for colorectal cancer: a systematic review. CRD Report 36. York: 2007.
  9. Kapidzic, A., et al. (2012). "Quality of life in participants of a CRC screening program." Br J Cancer 107(8): 1295-1301.
  10. Birkenfeld, S., R. G. Belfer, et al. (2011). "Factors affecting compliance in faecal occult blood testing: a cluster randomized study of the faecal immunochemical test versus the guaiac faecal occult test." J Med Screen 18(3): 135-141.
  11. Harden, E., A. Moore, et al. (2011). "Exploring perceptions of colorectal cancer and fecal immunochemical testing among African Americans in a North Carolina community." Prev Chronic Dis 8(6): A134.
  12. Hol, L., V. de Jonge, et al. (2010). "Screening for colorectal cancer: comparison of perceived test burden of guaiac-based faecal occult blood test, faecal immunochemical test and flexible sigmoidoscopy." Eur J Cancer 46(11): 2059-2066.
  13. Hughes, K., B. Leggett, et al. (2005). "Guaic versus immunochemical tests: faecal occult blood test screening for colorectal cancer in a rural community." Aust N Z J Public Health 29: 358-364.
  14. Wong, M. C., G. K. John, et al. (2012). "Changes in the choice of colorectal cancer screening tests in primary care settings from 7,845 prospectively collected surveys." Cancer Causes Control 23(9): 1541-1548.
  15. Wong, M. C., K. K. Tsoi, et al. (2010). "A comparison of the acceptance of immunochemical faecal occult blood test and colonoscopy in colorectal cancer screening: a prospective study among Chinese." Aliment Pharmacol Ther 32(1): 74-82.
  16. Levin TR, Connell C, Shapiro JA, Chazan SG, Nadel MR, Selby JV (2002). Complications of screening flexible sigmoidoscopy. Gastroenterology 123: 1786-1792.
  17. Broadstock, M. Computed tomographic (CT) colonography for the detection of colorectal cancer – a Technical Brief. NZHTA Technical Brief 2007; 6(6)

Appendices

None.

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