National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Clinical Practice: Quality requirements




Скачать 395.18 Kb.
НазваниеNational Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Clinical Practice: Quality requirements
страница4/7
Дата06.09.2012
Размер395.18 Kb.
ТипДокументы
1   2   3   4   5   6   7

Table 2. NACB recommendations: Quality requirements for Assay Validation, Internal Quality Control and Proficiency Testing

Requirements


Recommendations

Comments / specific examples

References

Assay validation








Well-characterized methods

Prior to their introduction in routine clinical practice, both immunoassay and immunohistochemical methods must be validated by defined and well characterized protocols that meet regulatory guidelines [e.g. Food and Drug Administration (FDA) approval in the United States, European Community (CE) marking in Europe].


It is critically important that methods are properly validated prior to their introduction to avoid misleading reports both in routine clinical practice and in the scientific literature. Failure to have done so accounts for some of the past issues with diagnostic tests, particularly for immunohistochemistry and fluorescence in situ hybridization (FISH) testing.


(30)


Methods for immunohistochemistry should be particularly carefully described if appropriate high quality reference materials are not available.


For example, tissue arrays with variable tumor marker amounts can be used.

(30)


Internationally recognized guidelines for the performance of immunohistochemical tests should be adopted where these are available.


The American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) have recently developed such guidelines for the tissue measurement of HER2. [See Breast Cancer section.]

(50)

Internal Quality Control











Assessment of reproducibility

Within-run variability <5%; between-run variability <10%.

Manual and/or research assays may be less precise but PT data suggests these targets should be readily achievable for most analytes.


(1, 17)

Established objective criteria for assay acceptance

Limits for assay acceptance should be pre-defined and preferably based on logical criteria such as those of Westgard. [For further detailed discussion and examples, see (51, 52).]


IQC data should be recorded, inspected and acted upon (if necessary) prior to release of any clinical results for the run.

(1, 16)

Appropriate number of IQC specimens.


The number of IQC specimens included per run should allow identification of an unacceptable run with a given probability acceptable for the clinical application.





(1, 16)

Specimens closely resembling authentic patient sera

QC material not provided by the method manufacturer is preferable. At least one authentic serum matrix control from an independent source should be included in addition to any QC materials provided by the method manufacturer.

Kit controls may provide an overly optimistic impression of performance, particularly if they are prepared by adding standard to an artificial matrix.


(1, 53)

IQC specimens of concentrations appropriate to the clinical application.

Negative and low positive controls should be included for all tumor markers. The broad concentration range should also be covered and IQC specimens should ideally include a high control to assess the accuracy of dilution.


Where clinical decision points are commonly employed (e.g. PSA, 0.1 and 3 or 4 g/L; AFP, 5-8 kU/L; hCG, 5 U/L), IQC specimens of these concentrations should be included.

(1)
Proficiency Testing










PT specimens of appropriate analyte concentration

Concentrations should assess performance over the working range.

Distribution of occasional specimens of high concentration to check linearity on dilution and of specimens containing analyte-free serum to check baseline security for certain analytes (e.g. AFP, hCG) is desirable.


(1)

PT specimens closely resembling authentic patient sera

PT specimens should ideally be prepared from authentic patient sera, which for tumor markers may require dilution of high concentration patient sera into a normal serum base pool.

PT specimens prepared by spiking purified analyte into serum base pools provide an overly optimistic impression of between-method performance (e.g. for CEA, mean CVs of 14% cf 20% for pools containing patient sera)


(1, 53)

PT specimens that are stable in transit

Evidence of the stability of PT specimens in transit should be available.

Stability in hot climates is particularly relevant for hCG and free PSA, but reliable data should be available for all tumor markers.


(1, 17)

Accurate and stable target values

The validity of the target values (usually consensus means) should be demonstrated by assessing their accuracy, stability and linearity on dilution.

Accuracy should be assessed by recovery experiments with the relevant International Standard [see Table 2], stability by repeat distribution of the same pool and linearity by issue of different dilutions of the same sera in the same serum base pool. Issue of PT specimens containing the IS can also for some analytes elucidate the extent to which different methods recognise different isoforms (e.g. hCG, PSA).


(16)

Assessment of assay interferences

Occasional specimens should ideally be issued to check for interference (e.g. from heterophilic and other antibodies, high dose hooking, etc).

The volume of sera required may preclude undertaking this for all participants, but by distributing such specimens to a limited number of users of different methods, valuable information about method robustness can be obtained and the results subsequently provided to all participants.


(1)

Evaluation of interpretation as well as technical results is required for PT of immunohistochemical tests


The interpretation of the pathologist as well as the technical aspects of the test must be evaluated.

Since immunohistochemistry reports routinely include an interpretive comment, the accuracy of these should be rigorously and independently assessed.

(30)

Interpretative exercises and surveys

Occasional surveys are desirable to compare practice in difference laboratories.

PT schemes can make a powerful contribution to national audit by highlighting differences in reference intervals, reporting practice and interpretation of clinical results, particularly when the ethos of the schemes is educational rather than regulatory.


(1, 17)

Provision of relevant educational updates to all participants

Incorporating regular updates to participants on new developments relevant to provision of a tumor marker service is desirable and can be conveniently done in Comments sections accompanying reports.


Surveys of recent literature can provide a helpful monthly addition to PT reports.


(1, 17)


Table 3. NACB recommendations: Quality Requirements for minimizing risk of method-related errors in tumor marker results

Type of interference


Recommendations


Comment

Reference


Cross-reaction of closely related molecules

Manufacturers should provide clear information about the specificity of the antibodies used in their methods and data on cross-reactivity that is readily comparable with that of other methods.


Users should be aware of the characteristics of the methods used.


Often helpful (e.g. when measuring PSA or hCG) but differences in recognition of the cross-reacting isoforms are likely to contribute to numerical differences in results.

(15)

High dose hook effect

Laboratories should have in place defined protocols for identifying specimens that have “hooked”.

Tumor marker concentrations range over several orders of magnitude and for any tumor marker may exceed the capacity of the solid-phase. For conditions that are potentially fatal but curable (e.g. childhood hepatoblastoma and gestational trophoblastic neoplasia) failure to recognise extremely high tumour marker concentrations (AFP and hCG respectively) constitutes a critical clinical error (54, 55).

.

(15, 33)

Specimen carry-over

Laboratories should occasionally check the vulnerability of their tumor marker methods to carry-over from a preceding high concentration specimen.


Potentially a problem whenever very high concentration specimens are assayed.

(15, 56)

Interference from heterophilic or human anti-mouse antibodies (HAMA)

Laboratories should be aware of the possibility of interference from heterophilic or human anti-mouse antibodies, particularly when results are not in accord with the clinical picture. Where interference is suspected this should be investigated, e.g. by re-assaying the specimen


  1. After treatment with commercially available antibody blocking tubes

  2. After addition of further immobilized normal, non-immune serum, Protein A or Protein G

  3. After precipitation of immunoglobulins with polyethylene glycol (PEG)

  4. In a different method, preferably using a different methodology (eg radioimmunoassay)

  5. At several dilutions to assess linearity on dilution




Falsely high or low results may be obtained for patient specimens containing anti-IgG antibodies capable of reacting with antibodies used in the assay. Such antibodies may be of particularly high titre in patients who have undergone treatment with mouse monoclonal antibodies for imaging or therapeutic purposes. Serious clinical errors as a result of failure to recognise such interference have been most frequently reported for hCG and CA125. A high degree of suspicion is usually required for identification, which is facilitated by good communication between clinical and laboratory staff.


(15, 56)


Table 4. NACB recommendations: Quality requirements in the post-analytical phase

Requirements


Recommendations

Comments / specific examples

References
Factual requirements







Clinical information from the requesting doctor

Brief clinical information indicating the source of the suspected/diagnosed malignancy and the treatment stage (e.g. pre-op, post-op, pre-chemotherapy) should accompany the specimen.


Such information is essential if any laboratory interpretation is to be made and may help to identify occasional laboratory errors (e.g. mis-sampling on an analyser).

(1)

Availability of appropriate reference intervals

Reference intervals should be appropriately derived using an appropriate healthy population.


Group reference intervals are usually most relevant for cancer patients pre-treatment, after which the patient’s own individual “baseline” provides the most important reference point for interpretation of marker results. If this is well established, increases even within the reference interval may be significant. Even if the marker is below the ‘normal’ or usual cut-off value any sustained increase must be treated as a possible relapse, provided the measurement procedure is the same (57). Reporting of critical increases of tumor marker concentrations, taking both the analytical performance of the test and the individual reference intervals (under specified clinical conditions, e.g. post-chemotherapy) into consideration contributes to earlier diagnosis of relapse.


(1, 57)




Reference intervals must be included when reporting results for immunohistochemical markers.


Reference intervals may include internal reference materials, e.g. normal ducts in breast tissue, and specify what staining they should have.


(30)

Interpretation criteria for immunohistochemical tests


Interpretation criteria must be well documented and must be clearly stated in the clinical report.

For Her-2/neu testing by FISH, for example, it is essential to define clearly what the appropriate ratio of Her-2 signals/CEP 17 signals is for classification as unamplified (2.0 for Vysis probes), borderline amplified, etc.


(30, 50)

Knowledge of what constitutes a significant change

The percentage increase or decrease that constitutes a significant change should be defined and should take account of both analytical and biological variation (58) and (51). Laboratories should be willing and able to advise on this issue.


The percentage increase or decrease that constitutes a significant change varies between tumor markers mainly due to the differences in the magnitudes of their biological variation (59-61).


A confirmed increase or decrease of  25% is frequently considered to be of clinical significance (16) but more work is required in this area, the importance of which has recently been illustrated for PSA (17).


(1, 60, 61)

Defined protocol when changing methods

Laboratories should have a defined protocol when changing tumor marker methods. Communication with the main users should always be sought before a changeover of method is undertaken. Ideally laboratories should avoid changing tumor marker methods unless essential.


This may necessitate analyzing the previous specimen by the new method or requesting a further specimen to re-establish the baseline and/or confirm the trend in marker level. If the results are significantly different it may be necessary to run old and new methods in parallel for a defined changeover period, an approach that also helps clinicians become accustomed to the new values.


(1)

Knowledge of tumor marker half-lives

Laboratories should be able to provide calculated tumor marker half-lives or doubling-time for the markers for which these are relevant (e.g. AFP, hCG, PSA, CA125).


Half-lives are defined as the time to 50% reduction of circulating tumor marker concentration following complete removal of tumor tissue. [Calculation of tumor marker half-lives may be irrelevant if a 50% reduction does not represent a significant change.]


(1)

Objective audit of tumor marker utility

Laboratories should be involved in on-going audit of the clinical utility of the results they provide.


This remains a priority and is being considered by a number of professional organizations.

(1, 9)
Reporting requirements







Cumulation of tumor marker results

Laboratories should provide fully cumulated tumor marker results. User-friendly graphical representations may also be helpful.

Helpful reports facilitate interpretation and communication between laboratory and clinic. It is helpful if the reports incorporate any brief clinical information available, particularly dates of operation etc.


(1)

Tumor marker method used


Laboratories should indicate the method used on the report form and highlight whether any change of method is likely to have affected interpretation of the trend in marker result.


As above.

(1)

Recommendations as to the appropriate frequency of tumor marker measurements


Laboratories should be willing to advise on the frequency of monitoring and the need for confirmatory specimens.

An apparent rise in marker concentration should always be confirmed by repeat measurement at a defined interval.


(1)

Communication between laboratory and clinical staff

Laboratories should always welcome and encourage good communication with clinical users of the service.

Good communication facilitates appropriate use of these (and other) tests. Telephoning results to the relevant clinician may in some cases be desirable.


(1)


Table 5. WHO International Standards (IS) and Reference Reagents (RR) for major tumor markers


Tumor marker

Code

Year established


Description

Reference

AFP

IS 72/225

1972

Crude cord serum (50%)

(62)

CA125

-

-

-

-

CA15-3

-

-

-

-

CA19-9

-

-

-

-

CA72-4

-

-

-

-

CEA

IRP 73/601

1973

CEA purified from liver metastases to primary colorectal cancer

(63)

hCG

IS 75/537

1975

Purified urinary hCG, contaminated with hCG and hCGn

(64)

hCG

IS 75/569

1975




(64)

hCG

IS 75/551

1975




(64)

hCG

IRR 99/688

2001

Highly purified urinary hCG, free from nicked forms and free subunits

(20)

HCGn

IRR 99/642

2001

Highly purified urinary hCG, partially degraded, missing peptide bonds in the hCG-40-50 region

(20)

hCG

IRR 99/720

2001

Highly purified urinary hCG, dissociated from hCG

(20)

hCG

IRR 99/650

2001

Highly purified dissociated urinary hCG, free from intact dimeric hCG, hCG and hCGn

(20)

hCGn

IRR 99/692

2001

Partially degraded hCG, missing peptide bonds in the hCG-40-50 region

(20)

hCGcf

IRR 99/708

2001

Residues hCGn-6-40, joined by disulphide bonds to hCGn-55-92

(20)

PSA

IRR 96/670

2000

90:10 ratio of bound : free PSA

(21)

fPSA

IRR 96/668

2000

Purified free PSA

(21)


International Standards and Reference Reagents are available from the National Institute for Biological Standards and Control, Potters Bar, Herts, UK [http://www.nibsc.ac.uk/catalog/standards/preps/sub_endo.html]


[hCG, human chorionic gonadotropin; IS, International Standard; hCGß, hCG ß-subunit; IRP, International Reference Preparation; hCG, hCG -subunit; hCGn, nicked hCG; hCGßn, nicked hCG ß-subunit; and hCGßcf, hCG ß-core fragment; PSA, prostate specific antigen; fPSA, free prostate specific antigen
1   2   3   4   5   6   7

Похожие:

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Clinical Practice: Quality requirements iconClinical Practice 4: Multi-system Care

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Clinical Practice: Quality requirements iconHerald of the mechnikov saint-petersburg state medical academy (profilactical and clinical medicine)
«The Mechnikov Saint-Petersburg State Medical Academy of the Federal Agency for Public Health and Social Development of the Russian...
National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Clinical Practice: Quality requirements iconHerald of the mechnikov saint-petersburg state medical academy (profilactical and clinical medicine)
«The Mechnikov Saint-Petersburg State Medical Academy of the Federal Agency for Public Health and Social Development of the Russian...
National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Clinical Practice: Quality requirements iconHerald of the Mechnikov Saint-Petersburg State Medical Academy profilactical and clinical medicine
«Mechnikov Saint-Petersburg State Medical Academy of the Federal Agency for Public Health and Social Development of the Russian Federation»,...
National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Clinical Practice: Quality requirements iconHerald of the Mechnikov Saint-Petersburg State Medical Academy (profilactical and clinical medicine)
«Mechnikov Saint-Petersburg State Medical Academy of the Federal Agency for Public Health and Social Development of the Russian Federation»,...
National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Clinical Practice: Quality requirements iconHerald of the Mechnikov Saint-Petersburg State Medical Academy (profilactical and clinical medicine)
«Mechnikov Saint-Petersburg State Medical Academy of the Federal Agency for Public Health and Social Development of the Russian Federation»,...
National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Clinical Practice: Quality requirements iconSchool of Biomedical and Clinical Laboratory Sciences

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Clinical Practice: Quality requirements iconBiology 333 – Clinical Laboratory Techniques

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Clinical Practice: Quality requirements iconFellowship Programme in Pathology (Clinical Biochemistry) King Saud University

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Clinical Practice: Quality requirements iconClinical and laboratory study hirudotherapy in treatment of chronic apical periodontitis

Разместите кнопку на своём сайте:
Библиотека


База данных защищена авторским правом ©lib.znate.ru 2014
обратиться к администрации
Библиотека
Главная страница