A new Nordic project – common reference intervals for 25 common serum parameters

Is your laboratory willing to participate in a joint effort to determine reference intervals for the common clinical chemistry analytes, which can then be used in all Nordic countries? In that case, this is the great opportunity!

On Mars 27^th last year the first meeting in a new Nordic project group, supported by the Scandinavian Society of Clinical Chemistry, with this aim, was held. The national societies of clinical chemistry in the Nordic countries have appointed the members of the project group, and these will function as national contact persons (in alphabetical order, see address list with telephone number, fax and Email address in the back): Peter Felding (secretary), Leifur Franzson, Veli Kairisto, Per Hyltoft Petersen, Pål Rustad (leader), Gunnar Skude.

The chosen parameters for this project are:

* for the enzymes IFCC-methods at 37° C (IFCC reference methods as recommended by the Nordic enzyme committee to be implemented by January 2000) or Vitros methods must be used.

Earlier a similar project, "The Nordic protein project", has been carried out: Recently there was an attempt to start a similar project for hormones, but the variety of methods, traceability problems and heterogeneity of the analytes made the attempt a failure. Why has there not been an attempt to do the same for the simplest analytes, where all these problems are much smaller? It is not easy to answer, but certainly the time is in for such an attempt.

During the years we have, through quality assurance work, concentrated on the improvement of the accuracy of analytical results, but the limits which these results are compared to have gained less attention. An investigation made in Norway on reference intervals in the individual laboratories related to their analytical quality, showed that the variation in reference intervals are far greater than it should be, taking analytical quality into account. Similar investigations done in other Nordic countries have also shown this discrepancy.

Already in 1997 Peter Felding (DK) made a proposition on how such a project could be realised in Denmark. His suggestion was adopted by our group and is now the basis of this project which in summary is as follows

• Each participating laboratory will collect 25-50 reference samples from reference persons evenly distributed in age and sex. The material will be serum for all persons, but we also want Li-heparin plasma to be collected for about 10% of the persons to investigate possible differences between materials. EDTA-blood for DNA-testing will also be collected for possible later use. The laboratories should primarily use vacuum collection tubes without gel or other additives (if this is not available, routine equipment may be used). The type of sample collection tubes should be specified.. The collected samples necessary for the laboratory to analyse the samples, and in addition 10 tubes each 1ml for each person, may be frozen for max 1 month at 020° C (indefinite time at –80° C). The 10 tubes are to be sent on dry ice to DEKS for archiving at -80° C for later use (control of suspect results and possible other projects). The material will be owned by the Scandinavian Society of Clinical Chemistry after the project has ended.
• You will receive 5 control sera: One with low (LOW), two with intermediate (CAL and X) and one with high (HIGH) concentration in addition to a serum pool from women using P-pills (P).
• CAL (FHK97) is a serum pool where most of the parameters have been measured by reference methods (used as A serum in the Labquality in September 1997 survey (described in EQAnews 1998, 9 no. 3: page 39-42).
• X is a serum pool for the future. It will be available for many years for laboratories to verify traceability to the new reference intervals.
• HIGH is made by concentrating a serum pool by removing water by freezing.
• LOW is made by diluting HIGH 1:2 with 80 mmol/L NaCl and 1 mmol/L CaCl₂ in water.
• P is a control with somewhat different characteristics than the other pools used, and as such will add quality to the control system of the project.
• Samples and controls should be measured in one series for each parameter. CAL should be measured in 10 replicates, the others in 3, all evenly distributed throughout the series.
• The data for the reference persons, samples and measurement method are to be registered, preferably directly via Internet or if Internet is not available by using a spread sheet (by E-mail or diskette). As a last possibility registration may be done on paper.

• Correcting all results by using CAL as a calibrator (the quotient of target and mean value of CAL multiplied by all results for the laboratory for each parameter).
• Quality tests: Linearity (HIGH/LOW - quotient should be near 2 except for sodium and calcium), analytical precision (replicates of all controls).
• Finding possible geographical-, sex - and age related differences (among others) in the reference values.
• Finding reference limits based on 2.5 and 97.5 percentiles of the distribution of reference values after rejecting all results that not fulfil the quality requirements.

The data base will be made available on request to everybody with a reasonable intention.

The response to each laboratory will consist of which of the results from the laboratory have been used in the common pool to calculate reference intervals, and the quality achieved on each method. On the basis of the achieved quality and/or possible geographical differences, guidelines will be given, as to whether the calculated new reference intervals can be used unchanged by the laboratory or if there are possible reasons for not doing so.

A limited number of laboratories from each Nordic country will receive this invitation to participate. These laboratories with the largest repertoire of the 25 parameters and with possibilities of data registration by Internet, will be preferred as participants. We anticipate the following numbers of laboratories from each country to join the project: Denmark - 40, Finland – 40, Island – 3, Norway – 40 and Sweden - 60.

To carry it through, this project will cost money, especially because we want the reference limits to have a long life span. Therefore each participating laboratory have to pay 3500.- Danish crowns to participate. Each laboratory have to carry the expenses to collect the reference samples and perform the measurements. The payment will have to be done in advance in order to pay for the materials and the distribution, etc. Even if this is an expense, we mean that by the end of the project, laboratory medicine as well as each participating laboratory will have gained valuable information.

All participating laboratories will in the autumn this year receive the following:

• Detailed instructions on how to perform with the project
• Information to potential reference persons
• Questionnaire to the reference persons
• Sample tubes for storing samples to be frozen
• Labels
• Adequate paper forms for registration of data (if necessary diskette with spread sheet)
• Control materials (9 tubes) on dry ice. These will be in a separate delivery (see national instructions).

We want the attached questionnaire to be answered before June 1^st and returned irrespective of your laboratory's participation to make sure that you have received this letter.

We strongly recommend all of you to answer YES to participate, - actually we expect it! There should be all reasons to be able to realise this project if we get the positive response that we hope and believe.

All suggestions to make the project better will be accepted with gratitude!

The project's web site on internet is: http://home.sol.no/~rustadp/ref/refprosj.html.

Klinisk Kemi i Norden, no 4, vol. 10, 1998

On behalf of the project group:

Best regards

Pål Rustad

Enclosures:

1. Letter from Ebba Nexø, chairman of the Scandinavian Society of Clinical Chemistry
2. Letter from the national organisation for external quality assurance
3. Project description

Tlf: 354 560 1838 Fax: 354 560 1810 E-mail: elino@rsp.is

Tlf: 47 22119480 Fax: 47 22118189 E-mail: heidi.steensland@ioks.uio.no

Tlf: 45 4488 3310 Fax: 45 4453 5369 E-mail:deks-eqa@post8.tele.dk

Laboratory:______________________________________________Labquality no.: _______

Address:____________________________________________________________________

Contact person in the laboratory:_________________________________________________

Telephone:_______________ Telefax: ________________ E-mail:_____________________

 ________________________________________________________________________

Is your laboratory willing to participate by collecting 25-50 samples from reference persons and analyse them in addition to mailed control materials on those clinical chemical parameters from the list below that are on the repertoire of the laboratory? Yes No

Please encircle the parameters that you will NOT be able to measure:

Do you have access to Internet? Yes No

If no: Do you have access to Excel spread sheet? Yes No If yes, which version?________

If you do not have Excel, have you access to another spread sheet? Yes No

If yes, which and what version?:________________________________________________

The intention is to mail you 2x5 mL CAL, 5 mL X, 2x2.5 mL each of HIGH, LOW and P.

Is this sufficient to do the measurements on your routine instrument? Yes No

If no, how much do you need in addition to the above?________________________________

Does the laboratory have access to a -80° C freezer? Yes No

Which month will be best for you to collect reference samples and receive control samples (indicate priority with 1, 2, 3 for each month – 1 the best month)?

October 1999 - January 2000 - April 2000

For Norway:

Please return questionnaire before 1. June 1999 to Heidi , snail-mail address:

Heidi Steensland

Klinisk kjemisk avd.

Ullevål sykehus

P0407 Oslo