Reference change values Fraser, Callum G.
Clinical chemistry and laboratory medicine,
05/2012, Letnik:
50, Številka:
5
Journal Article
Recenzirano
Reference change values (RCV) provide objective tools for assessment of the significance of differences in serial results from an individual. The concept is simple and the calculation easy, since all ...laboratories know their analytical imprecision (CVA) and estimates of within-subject biological variation (CVI) are available for a large number of quantities. Generally, CVI are constant over time, geography, methodology and in health and chronic stable disease. The formula is RCV=21/2 · Z · (CVA2 + CVI2)1/2, where Z is the number of standard deviations appropriate to the probability. Correct interpretation of the semantics describing the clinical use of RCV is vital for selection of the Z-score. Many quantities of clinically importance exist for which good estimates of RCV are unavailable. Derivation of CVI may be difficult for such quantities: flair and imagination are required in selecting populations with chronic but stable disease on whom CVI can be determined. RCV can be used for delta-checking and auto-verification and laboratory information management systems (LIMS) can be adapted to do this. Recently, log-normal transformation to obtain unidirectional RCV has been used. Gaps in knowledge of RCV still require filling since the need for measures of change is clearly expressed in guidelines.
Faecal hemoglobin concentrations (f-Hb) can be quantitated using faecal immunochemical test for haemoglobin (FIT) analytical systems. FIT are of proven value and widely used in colorectal cancer ...(CRC) screening. Several factors affect f-Hb including sex, age, deprivation, geographical region, and FIT system. Thus, FIT data may not be transferable. Women are disadvantaged in programmes using a single f-Hb threshold for all participants, but risk scoring or sex stratified thresholds could be used to minimise this problem. In addition, low but detectable f-Hb, below the threshold, implies future risk of CRC. In several countries, where colonoscopy resources are constrained, FIT are now accepted as of added value in assessment of patients presenting in primary or secondary care with symptoms, although some serious colorectal disease is missed. Elevated f-Hb in the absence of any discernible colorectal lesions is common and has been found in several diseases with a systemic inflammatory component, including circulatory, respiratory, digestive, neuropsychological, blood and endocrine diseases, and others. There is growing evidence for the value of f-Hb in post-polypectomy surveillance, potentially saving costs and colonoscopy. There may be a role for FIT systems which have lower limits of detection than currently available methods. The faecal material remaining in FIT specimen collection devices could be used for further studies, including assessment of the microbiome. The estimation of f-Hb is now a mature investigative tool but further research will undoubtedly expand applications of value.
Fraser talks about the appropriate use of fecal immunochemical testing (FIT). Substantial evidence has accumulated over the last decade that a low fecal hemoglobin concentration is reassuring in ...symptomatic patients, as many studies show a very high negative predictive value for significant bowel disease. Moreover, a very high fecal hemoglobin concentration should lead to urgent referral. Fecal immunochemical testing has been widely introduced as a routine investigation available to general practitioners throughout the UK and is facilitating the referral for colonoscopy for those patients who would most benefit. No diagnostic test is perfect, however, and a few cases of clinically important bowel disease will have a "negative" FIT result. The FIT result should not be interpreted in isolation, and relevant clinical indications for referral should be heeded. Further, for some patients with a negative FIT result, safety-netting strategies-in which people at low risk, but not no risk, of having cancer are actively monitored in primary care to see if the risk of cancer changes-may be required.
Colonoscopy is a relatively scarce resource in many countries, including Scotland, and a simple investigation which would aid general practitioners in particular in decision-making as to which ...patients presenting with lower bowel symptoms warranted referral would be of much help. Faecal immunochemical tests for haemoglobin (FIT) have many advantageous characteristics and are now proven to be of considerable value in the timely assessment of patients with symptoms of lower bowel disease. Quantitative FIT provide numerical estimates of faecal haemoglobin concentration (f-Hb) and, at low f-Hb cut-off, FIT have high sensitivity for colorectal cancer (CRC) and could be used as a rule-in test to stimulate rapid referral, especially when symptoms are suggestive of serious bowel disease. Perhaps more importantly, a low f-Hb gives considerable reassurance that significant bowel disease (CRC + higher-risk adenoma + inflammatory bowel disease) is absent and further investigation may not be warranted: however, no test is perfect, so some cases will remain undetected using FIT alone and robust safety netting is required, possibly including watching and waiting, referral to clinics in secondary care, or a repeat FIT. Moreover, the FIT results should not be taken in isolation, but clinical impressions and the results of other investigations, probably including the full blood count, should be considered. Challenges still exist, however, and harmonisation of aspects of the available FIT analytical systems is required. Moreover, a number of seemingly valid clinical concerns remain and these require resolution through further research and reporting of studies done in real clinical practice.
The setting of analytical quality specifications in laboratory medicine has been a topic of discussion and debate for over 50 years: 15 years ago, as the subject matured and a profusion of ...recommendations appeared, many of them from expert groups, it was realised by a number of leading professionals that there was a need for a global consensus on the setting of such specifications. The Stockholm Conference held in 1999 on “Strategies to set global analytical quality specifications in laboratory medicine” achieved this and advocated the ubiquitous application of a hierarchical structure of approaches. The hierarchy has five levels, namely: 1) evaluation of the effect of analytical performance on clinical outcomes in specific clinical settings; 2) evaluation of the effect of analytical performance on clinical decisions in general using a) data based on components of biological variation, or b) analysis of clinicians’ opinions; 3) published professional recommendations from a) national and international expert bodies, or b) expert local groups or individuals; 4) performance goals set by a) regulatory bodies, or b) organisers of external quality assessment (EQA) schemes; and 5) goals based on the current state of the art as a) demonstrated by data from EQA or proficiency testing scheme, or b) found in current publications on methodology. This approach has been much used since its wide promulgation, but there have been ongoing criticisms and new developments. The time seems right for an objective reappraisal of recommended strategies to set analytical performance goals.
This study has attempted to assess the effectiveness of quantitative faecal immunochemical tests (FIT) for triage of people presenting with lower abdominal symptoms, where a referral to secondary ...care for investigation of suspected colorectal cancer (CRC) is being considered, particularly when the 2-week criteria are not met.
We conducted a systematic review following published guidelines for systematic reviews of diagnostic tests. Twenty-one resources were searched up until March 2016. Summary estimates were calculated using a bivariate model or a random-effects logistic regression model.
Nine studies are included in this review. One additional study, included in our systematic review, was provided as 'academic in confidence' and cannot be described herein. When FIT was based on a single faecal sample and a cut-off of 10 μg Hb/g faeces, sensitivity estimates indicated that a negative result using either the OC-Sensor or HM-JACKarc may be adequate to rule out nearly all CRC; the summary estimate of sensitivity for the OC-Sensor was 92.1% (95% confidence interval, CI 86.9-95.3%), based on four studies (n = 4091 participants, 176 with CRC), and the only study of HM-JACKarc to assess the 10 μg Hb/g faeces cut-off (n = 507 participants, 11 with CRC) reported a sensitivity of 100% (95% CI 71.5-100%). The corresponding specificity estimates were 85.8% (95% CI 78.3-91.0%) and 76.6% (95% CI 72.6-80.3%), respectively. When the diagnostic criterion was changed to include lower grades of neoplasia, i.e. the target condition included higher risk adenoma (HRA) as well as CRC, the rule-out performance of both FIT assays was reduced.
There is evidence to suggest that triage using FIT at a cut-off around 10 μg Hb/g faeces has the potential to correctly rule out CRC and avoid colonoscopy in 75-80% of symptomatic patients.
PROSPERO 42016037723.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Faecal immunochemical tests for haemoglobin (FIT), as an adjunct to clinical information, assist in the triage of patients presenting in primary care with lower abdominal symptoms. ...Controversy remains regarding whether and which qualitative and quantitative FIT can be used, which groups of patients would benefit most from FIT, whether FIT should be done in primary and/or secondary care, and how FIT should be incorporated into diagnostic pathways. Controversy also exists as to the optimum cut-off used for referral for colonoscopy. A single sample of faeces may be sufficient. Reporting of results requires consideration. FIT provide a good rule in test for colorectal cancer and a good rule out test for significant bowel disease, but robust safety-netting is required for patients with negative results and ongoing symptoms. Risk scoring models have been developed, but their value is unclear as yet. Further evaluation of these topics is required to inform good practice.
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