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
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 December 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

<< Clinical EffectivenessEthical analysis >>

Costs and economic evaluation

Authors: Principal Investigators: Anna-Theresa Renner, Ingrid Rosian-Schikuta, Investigators: Nika Berlic, Neill Booth, Valentina Prevolnik Rupel


Cost-effectiveness studies generally find that both FIT and FOBT have relatively favourable ICERs when compared with no screening. Although neither type of screening modality is always more cost effective than the other, cost-effectiveness models tend to suggest FIT has more favourable ICERs. However, it should be noted that, compared to gFOBT, the added test sensitivity of FIT is accompanied by a need for a higher capacity in undertaking diagnostic colonoscopies. Therefore, there is increased up-front resource use, potential harm and cost associated with these colonoscopies which will normally be undertaken when screening using FIT (in comparison to gFOBT). FIT also lacks direct evidence from randomised trials concerning its effect on mortality. With the advent of increasingly expensive treatments, the cost-effectiveness both of FIT and gFOBT is likely to increase. On the other hand, although FIT is likely to detect more asymptomatic cancers than gFOBT, this increased test sensitivity increases diagnostic testing costs and also increases the possible dangers associated with screening-induced colonoscopy.


Colorectal cancer (CRC) is the second most frequent malignancy in developed countries. The overall burden of disease in Europe caused by CRC is high due to both, a high incidence rate and a high mortality. Estimates show that over 450,000 people were diagnosed with, and over 223,000 died of, CRC in Europe in 2008. Hence, the number of new CRC cases was nearly 51 per 100,000 Europeans and the mortality of CRC was over 25 per 100,000 Europeans {1}. Screening and detecting adenomas or polyps in an average risk population has the potential to reduce the individual, social and financial burden of disease.

The aim of this Cost and economic evaluation domain is to summarise the results of a systematic literature search concerning the costs and cost-effectiveness of immunochemical versus guaiac-based faecal occult blood tests used for CRC screening. This is done to gain insight into the results and the study design of published cost-effectiveness models and support decision making on screening. The domain reviews published cost-effectiveness studies that include a (direct or indirect) comparison of a Faecal Immunochemical Test (FIT) and a Guaiac-based Faecal Occult Blood Test (gFOBT) {2}.



The collection scope is used in this domain.

TechnologyFecal 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 technologyScreening

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 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)

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.



  • 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


  • 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)


  • 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


  • 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


  • 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


  • 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


  • 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
E0001Resource utilizationWhat types of resources are used when delivering the assessed technology and its comparators (resource use identification)?yesWhat types of resources are used when delivering FIT and its comparators gFOBT and no screening(resource use identification)?
E0002Resource utilizationWhat amounts of resources are used when delivering the assessed technology and its comparators (resource use measurement)?yesWhat amounts of resources are used when delivering FIT and its comparators gFOBT and no screening (resource use measurement)?
E0003Unit costsWhat are the unit costs of the resources used when delivering the assessed technology and its comparators?yesWhat are the unit costs of the resources used when delivering FIT and its comparators gFOBT and no screening?
E0005OutcomesWhat are the incremental effects of the technology relative to its comparator(s)?yesWhat are the incremental effects of FIT relative to its comparator(s)gFOBT and no screening?
E0006Cost-effectivenessWhat is the incremental cost-effectiveness ratio?yesWhat is the incremental cost-effectiveness ratio (FIT versus gFOBT; FIT versus no screening; gFOBT versus no screening)?
E0007Cost-effectivenessWhat is the appropriate time horizon?yesWhat is the appropriate time horizon?
E0008Cost-effectivenessWhat is the method of analysis?yesWhat is the method of analysis?
E0004Indirect CostsWhat is the impact of the technology on indirect costs?nothe indirect costs are not considered because the study is carried out from the perspective of the health care payer/system; furthermore, if QALYs are used as outcome measure, there is discussion in the scientific community, that there might be double counting; additionally the decision makers, responsible for the implementation of a screening technology, are mainly interested in the costs for the health care system

Methodology description

The following elements will be assessed within the domain “Cost and Economic Evaluation” (ECO):

Result card


Research question


Resource use

What types of resources are used when delivering FIT and its comparator gFOBT?


Resource use

What amounts of resources are used when delivering FIT and its comparator gFOBT?


Unit costs

What are the unit costs of the resources used when delivering FIT and its comparator gFOBT?



What are the incremental effects of FIT relative to its comparator gFOBT?



What is the incremental cost-effectiveness ratio (FIT versus gFOBT)?



What is the appropriate time horizon?



What is the method of analysis?


Indirect costs are not covered to any great extent in this domain because a health-care payer perspective has been adopted in most of the studies found. The main reason for exclusion of indirect costs may be that most decision makers consider only health care resource costs in the base case for the evaluation of screening programmes and studies that include indirect costs are rare. With respect to this domain, decision makers who are responsible for implementing a screening program should be aware that the studies focus is almost entirely on the direct costs for the health care system, with little attention to potential wider economic impacts. Further details related to impact on budgets can be found from results card ORG7, from the Organisational aspects -domain.

Information sources

A systematic literature search was conducted using the CRD, Cochrane and PubMed databases to identify studies that are based on cost-effectiveness models comparing FIT with gFOBT.

The results of the “Survey for retrieving information on the use of technology in European countries” did not yield enough information on the costs of screening using FIT and gFOBT and were therefore not included in the analysis.

Quality assessment tools or criteria

In the systematic literature review, the focus was on cost-effectiveness studies published in peer reviewed journals. Reviews, letters, comments, etc., were not considered for inclusion in the analysis of evidence, although HTA reports as well as other literature were used to gain a further perspective (see, e.g., {5, 6}). The search strategy was validated by achieving consensus among the investigators and reviewers of the ECO domain. The quality of the included studies was not formally assessed here, the reasons being that cost-effectiveness studies are generally aimed at providing an input into informed decision making and that there are both strengths and weaknesses in existing checklists {7}. These studies are often highly context specific (i.e., specific to the country, population, health care system, perspective, etc. in which the decision is being made). As a consequence, a study on cost-effectiveness considered as high-quality according to a reporting-quality checklist (such as {8, 9}) but may not be highly relevant for a decision maker in a different decision-making or policy context. On the other hand, a study classed by a checklist as ‘low-quality’ might include the best available evidence for a specific decision-making situation and, therefore, make a relevant contribution to informing the decision. 

Analysis and synthesis

A systematic literature search was conducted using different scientific databases (CRD, Cochrane and PubMed) in June 2013. The search was specifically aimed at identifying peer-reviewed literature containing cost-effectiveness models focusing on population-based colorectal cancer (CRC) screening using FIT vs. gFOBt. Studies comparing other screening strategies (e.g., flexible sigmoidoscopy or computed tomographic colonography) with only one of the two relevant strategies, either FIT or gFOBT, were excluded as well as studies that were not based on decision-analytic modelling. Articles that solely report clinical outcomes and studies looking only at costs were excluded since the primary aim of this domain is to gain insight into the results and the study design of published cost-effectiveness models.

After the systematic literature was completed, extensive citation tracking and non-systematic searching was conducted. This additional search was essential because, at this point in time, a general consensus is lacking about one or more standard terms used for the relatively new immunochemical screening technology. In the literature different terms or abbreviations for screening for CRC with an immunochemical faecal occult blood test are used and some of these were only identified on the basis of the systematic search results; the most common are FIT (faecal immunochemical test), iFOBT (immunochemical faecal occult blood test) or FOBT with HemeSelect, which is a specific immunochemical test. The latter term is often used in older studies (until 2000), whereas FIT is frequently used in the most recent studies. The detailed search strategies can be found in the Appendix.

Figure 1: Literature search

pdf10936.Eco-Figure 1

The decision to exclude studies was based on main two criteria: (1) the study does not compare a guaiac-based faecal occult blood test with an immunochemical based faecal occult blood test and (2) the study does not include a cost-effectiveness model. Other reasons for exclusion were a lack of relevance for the European context, focus on a different disease, or the published work being case studies, congress presentations, editorial letters, etc. (see the Appendix for detailed selection criteria). After screening the abstracts and evaluation of the full texts, 16 relevant articles {10-25} could be identified and included in the review. {26-37}

The results presented in this domain are a review of the included models but do not include a meta-analysis. A meta-analysis, amongst other things, would neglect the fact that the costs (result cards 1-3), incremental effects (result card 4) and as a consequence the cost-effectiveness (result card 5) ratios are influenced by the study design (type of model, perspective, time horizon, population etc.) and the input parameters (sensitivity, specificity, compliance rate, etc.) {38}. Building a generic cost-effectiveness model for Europe was regarded as not feasible within the time constraints of this pilot Core HTA, due to the need to allow for the modelling of different health-care systems and the epidemiological differences found in European countries. It was therefore considered more useful to provide a comprehensive overview of the existing published cost-effectiveness models as support and starting point for country-specific models developed in national reports. 

Result cards

Resource utilization

Result card for ECO1: "What types of resources are used when delivering FIT and its comparators gFOBT and no screening(resource use identification)?"

View full card
ECO1: What types of resources are used when delivering FIT and its comparators gFOBT and no screening(resource use identification)?

Importance: Important

Transferability: Completely

Result card for ECO2: "What amounts of resources are used when delivering FIT and its comparators gFOBT and no screening (resource use measurement)?"

View full card
ECO2: What amounts of resources are used when delivering FIT and its comparators gFOBT and no screening (resource use measurement)?

Importance: Critical

Transferability: Not

Unit costs

Result card for ECO3: "What are the unit costs of the resources used when delivering FIT and its comparators gFOBT and no screening?"

View full card
ECO3: What are the unit costs of the resources used when delivering FIT and its comparators gFOBT and no screening?

Importance: Optional

Transferability: Not


Result card for ECO4: "What are the incremental effects of FIT relative to its comparator(s)gFOBT and no screening?"

View full card
ECO4: What are the incremental effects of FIT relative to its comparator(s)gFOBT and no screening?

Importance: Critical

Transferability: Partially


Result card for ECO5: "What is the incremental cost-effectiveness ratio (FIT versus gFOBT; FIT versus no screening; gFOBT versus no screening)?"

View full card
ECO5: What is the incremental cost-effectiveness ratio (FIT versus gFOBT; FIT versus no screening; gFOBT versus no screening)?

Importance: Critical

Transferability: Partially

Result card for ECO6: "What is the appropriate time horizon?"

View full card
ECO6: What is the appropriate time horizon?

Importance: Unspecified

Transferability: Unspecified

Result card for ECO7: "What is the method of analysis?"

View full card
ECO7: What is the method of analysis?

Importance: Unspecified

Transferability: Unspecified


The general limitation of model-based cost-effectiveness studies is that models represent a simplification of a complex reality. This limitation is clearly present in the Costs and economic evaluation domain where we included studies that use modelling to estimate the costs, effects and cost-effectiveness of colorectal cancer. For instance, many cost-effectiveness studies make the simplifying assumption that all colorectal cancers develop from adenomas, although this is unlikely to be the case {5}. A series of trade-offs have to be made, for instance, between complexity and transparency. Many of these models have been to some extent validated, or calibrated, against, e.g., estimates of efficacy in terms of CRC incidence or mortality from randomised trials and other literature. However, as there is no general means to validate or calibrate models in terms of their estimates of cost or cost effectiveness, readers should focus on their potential face validity given the inputs used, the extent to which models were transparently documented, and whether appropriate sensitivity analyses were performed. The benefit of model-based studies is that it allows the comparison of different screening tests where economic evaluations based on end-to-end trials might not be feasible. It enables researchers to put the two comparators in the same context (e.g. assuming the same quality of follow-up tests or cancer treatment), and therefore limit the analysis to the actual outcomes of the tests.

Issues relevant to numerous domains within this Core model include sensitivity and specificity, participation rate, age of the population to be screened, screening interval, different FIT thresholds. Below we highlight some of the issues from the literature which have some of the strongest effects on the estimates of cost and cost effectiveness.

It should be noted that the review presented in this domain is complicated by the fact that a majority of studies compare many screening modalities (e.g. faecal DNA test, flexible sigmoidoscopy, computed tomography colonoscopy, colon capsule endoscopy {13-15, 18, 20, 22, 23, 25}), rather than just FIT and FOBT. A difference is also discernible between those studies with a North American focus and those with a European focus. One of the main ways in which European studies may differ markedly from those in the US is in terms of the lower European level of health care and social care costs. For instance, the cost of testing kits, diagnostic procedures and both curative and palliative treatment may all be substantially higher in the US. The rate of increase in costs may also differ between Europe and the US, many studies have not incorporated the probable cost pressures caused by the new forms of chemotherapy {6}. Another culturally-specific issue is the pattern of adherence to screening protocols, for example, FOBT participation rates in Finland during the roll-out of a national screening programme were as high as 71% {40}, while in Italy adherence as part of a randomised controlled trial was recorded as 27% on average {41}. Most of the studies included in the review do not take into account that adherence, i.e., the level of participation in screening and post-screening protocols, may differ quantitatively {10-16, 18, 21-23, 25}, e.g., may depend on the screening modalities in question. However, even when studies do not assume perfect adherence relatively favourable estimates of cost-effectiveness are reported in base-case analyses {6}.

Given the use of a health-care payer perspective in many studies, when analysing costs, they naturally do not include costs which are borne by the patient or costs borne outside the health care system. Hence, in the studies found, many of the costs borne by individuals, which may vary according to the screening modality used, has not been taken into account in many models {5}. A variety of health-care-payer perspectives on costs was predominant in the studies found. It could also be informative if a societal perspective, which may include costs falling more widely both inside and outside the health-care system, would also have been investigated. It should be noted that the choice of a restricted perspective, such as the perspective of a health-care-payer, may affect both the ability to provide information on either static or dynamic economic efficiency, and the ability of estimates of cost-effectiveness to be usefully compared to analyses of other technologies which use a different or broader perspective.

There is still a dearth of information concerning health-related quality of life both for screening participants, as well as for individuals who undergo diagnosis and or treatment. One small-scale, now decades old, study of health-related quality of life amongst colorectal cancer patients is widely used in the estimates found in this literature review.

The choice between FIT and FOBT is complicated as both FIT and gFOBT are often used as generic names for a number of tests, for which the sensitivity and specificity, for example, vary. FOBT has had versions called Hemoccult ®, Hemoccult II and Hemoccult SENSA and FIT has been used with low-mid-high or other quantitative thresholds. The situation is complicated even further by the fact that there are different approaches of measuring the sensitivity and specificity of a screening test {33}.

Although a discount rate of 3% was widely used for both costs and benefits {10, 13, 16-18, 21, 24, 25}, in many of the studies reviewed here the rate of discount for costs and/or benefits was one of the parameters most influential on the resulting ICERs and, together with the chosen time horizon, careful consideration should be given to the applicability of the values used in the analysis {40}. The use of thorough sensitivity analyses concerning variations in discount rates is particularly advisable when a time horizon of extended duration is used.

It should also be remembered that estimates of the overall cost burden of initiating and maintaining a screening programme is usually considered to be beyond the scope of the ECO domain (see, e.g. {30}). The Core Model considers such costs within the Organisational domain.

Potential future research needs in the light of this systematic review:

  • Trial-based economic evaluations of FIT versus gFOBt, no screening, or opportunistic screening, with both mortality and morbidity endpoints (one such study, currently underway in Finland, is comparing gFOBT to no screening)
  • Thorough and transparent sensitivity analyses concerning variations in, e.g., discount rates and adherence 


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  • Systematic literature search

    pdf10936.ECO-Appendix 1

  • Selection Criteria

    pdf10936.ECO-Appendix 2

  • Study designs and results

    pdf10936.ECO-Appendix 3



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