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Quality control in the Scandinavian clinical chemical laboratories

L. ELDJ ARN and J. H. STR0~fME

Instilute of Clinical Bi«hemi.&try, R~hospitalet, University of Oslo, Norway

A program of quality contro! of the work done in Scandinavian clinica! chemical lahoratorit-s has gradually developed during the last 5-10 years. In this conttol scheme there are 3 levels:

The first leve! is in the laboratory itself. W e feel confident that a daily contro! scheme witbin the laboratory represents the fundamental hasis of tlris work, since production and contro! are dose t<• each other. This allows a continuous feed-back to improve all s teps in the analytical procedure. T o aid the accomplishment of su c h an in ternal quality contro!, 5 great hospital laboratories of the Scandinavian countries and t he Norwegian fìrm Nycgaard & Co., Osio, have cooperated in developing a contro} serum,

« Seronorm». The recommended values - the Facit - for more than 30 of its essential compounds are being worked out on the basis of the analytical results obtained by the mcntioned laboratories. These values form the basis n<.ot only for the use of Seronorm in determining the precision, hut also for checking the accutacy of the analytical proce­dures in the daily local control. In the J:t~acit, references are also given concerning the analytical procedure used, which to some extcnt infiucn­ces the choice of mcthods and brings a bout a standardization of the procedures.

The second leve) centers around larger hospital laboratories. H ere frequent regional interlahoratory controls a re carried out. E. g. in Norway rcgional controls of some 30 laboratories ha ve been carried out since 1963 t 1).

Later on in this Syn::posium, doctor Hyvarincn will report on regional screen­ings in Finland.

The thircl level is represented by internat ional surveys, in this case, nter-Scandinavian surveys. Under the auspices of the Scandinavian Society

for Clinica! Chemistry and Clinica! Physiology, our University hospital laboratory in Osio carried out 4 consecutive surveys since 1968, coverin g

A nn. l at. SuD eT. Sanjtd {1971) 7, 293-290

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294 !'TANilAIIIlTI.ZAZ IO:>;E L (':l:>; 11!111.1.0 Ili Q l III.ITÌ

up to 140 clinical chemical ho ·pita l laboratories (2) . Thcse surveys will continue once or twice a year.

Some of the results of our rcpeat«•d Norwegian urveys and of thc in tcr-Scandinavian surveys will be prescntcd hcrc.

F.xperimental de si[!n

Thc e:x.--pcrimental design of the e sm veys mu t b e carefully plannefl. Lyopbilized sera werc u sed as t est materia) in order t o secure stability of t.he compounds in question. Two sera (A and B) werc distributed in anl· poulcs under v acuum togethcr with two ampoules of water tu which known amounts of various cons t;tuents had bcen adùed. A total of 20 scrum cons tituents (15 uon-enzymic c~tmponcnts ami 5 enzymes) were included in tbe Scandinavian survcys and in tbc last Norwegian surveys.

As pointcd out, cacb participating labora tory has its own mteroal runn­ing control for establishing the precision of t hc method. Of course, intcr1a­b oratory cun trols m ay stimulate and help in this work. In ou r opinion , howevcr, tbc main goal of tbc larger surveys must b t> to establish thc routine p erformance Ctf tbe laboratories as a gr oup. i. e. to inform about thc various analy tical r esults a given serum would giYt, depending 011 tlw laboratory wherc it was analysed. Instructions wen thcrcfore gi" cn t <> tr cat ami assay tbc test serum as an ordinary serum spccimen. D uplicate analyscs were not permittcd unle!'s this was a routine procedure. Errors in accuracy as wcll as in precision are thcrcfurc includcd in thc r f's ults .

Comments on thl' presentation of the materia/

The s tatis tica! t reatment of th«· rcsults was donc on our I BM l L30 computer. It may be of some intercst that a « truncation» procedure was undcrtakcn in order to excludc greatly crroneous rcsults . The program excluded ali rPsults outside ±- 2 SP from tbc m ean of the primary materia), calculated a new m ean and SD of the rcmaining maten al, addf•d what had becn cut out and r epeated the procedure uotil no furthcr alteration of the mean occurrcd. B y this prt>ccdure a selected group cf rcsults was obtained, thc m can of which is ob,·;ously c1oser to the truc Yalnc than the mean of the total material.

E ach par ticipant r eccived a tahulation of it s own rrsults along with tbc statistica) data on the whul c material. In add'tic.n hc receivcd a fre­quency histogram for each con stitucnt a s well as a scatter diagram. This prescntation per011tted cach participant to relnte only bis own rcsults t o the complete material. The criteria for « allowablc rangcs of error» were dcfincd according to tbc formula proposed by T onks (3).

A. nn. Itt. Super. Saftìtà (1971 ) 7, ~93-2\19

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295

Comments on the res1tlts

On this occasion we want to stress a few aspects of tbc results. First, our longitudinal surveys of Norwegian laboratories in the period

1963- 1970 demonstrate a s triking improvemcnt in the quality of the rcsults. Fig. l shows that laboratolies with less than 60 % of all the results wtthin the allowable limits bave disappeared in this period, laboratories showing less than 81 % of all the resuJts within the allowable limita are disappearing, and nearly ali laboratories now provide 81-100 % of the results within the

Fig. l. - Participating Nor· wegian laboratories grouped according to the percentage of theis reported re· sults which fell wi­thin the allowable limita of error.

l 0 __r- 61-80% wlthin allow.Um.,

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stated allowable lunits. This improvement is of considerable interest because, as s tated by dr. Broughton m 1969, convincing evidence had pre· viously becn lacking that the vigorous application of quality contro! results in an overall improvement in the performance of the laboratories. With respect to Norway we feel confident that our data prove that a considerable improvement took piace, and that our screening activity has not been without significance.

Sec(.nd, in the case of tbc 15 non- enzymic componente, our consecutive screenings of the 140 Scandinavian laboratories demonstrate results which compare favourably with those obtained in previous interlaboratory surveys.

When comparing the resuJts from nearly 150 hospital laboratories of different size and with different staff and equipment, it is likely that, for each analysis, the materia! can be divided into two groups, one of signi· ficantly better quality than the other.

In order to test this possibility, the ùescrihed t runcation procedure was introduced. In the case of the 15 non-enzymic componente the exclu· ;;ion of only 7- 19 % of the r esults reduced the average coefficient of varia-

Amo. l st. Suoer. SanltA (1971) 7, ~9à-~9U

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296 SI.Oo'lJAROIZZAZIONE l! CONTROLLO DI QUALITA

tion to less than half (Table l). Thus, tbe « normalized truncatcd materia!» r eprescnting from 81-93 % of tbc total materia}, demonstrate coeflìcients of variation whicb may be consider ed highly satisfactory.

TABLE l

Average coefficient of variation (CV) for the 15 non-ensymic components obtained in tbe fìret tbree Scandinavian eurveys

T OTAL IU.TUlAL No.aJII'.ALn.En n t"'!'CCAT&o ••TE-UA.L

CV(%) cv(~.) l Pueent omitted (• )

Me an 12 .2 5.0 13

Range. 3. 1- 22.6 1.5- 10 .5 7- 19

( • ) Pe-nt Outoide the odju•ted dittribution curveo.

In ow opinion this demonstrates tbat tbc analytical procedures and metbods at present in common use in Scandinavia for the non·enzymic componente are satisfactory. Moreover, it seems likely tbat minor impro· vements in a small group of laboratories may lead to a good quality of performance.

Third, wc also included some enzymes in our interlaboratory surveys. The var1ous results obtained for each enzyme were sub- grouped according to tbc metbods used. Stili only 25- 50 % of tbc results werc inside the allowable percentage of error. The truncation procedure was also applied in the case of the enzymes. Of course, also in this case a reductiou in the average coefficient of variation was obtained by this procedure, but tbc results could still not be considered acccptable. Thus it was not possible t o defiuc a largcr group of laboratorics in which t he cnzyme r csults could be considered satisfactory. In our opinion this finding shows that some new approach is needed to improve enzyme dcterminations.

It is generally felt that systematic errors play a dominant role m the enzyme assays. Such systematic errors bave been tacitly accepted as unavoidable by many laboratories to the extent that they claim to bave established their own « normal range». Ali tbc participating laboratories in our survey were asked to report tbc upper limit of their« normal range», and the values for the enzyme activities were calculat ed as percent of the respective upper Hmit. It will be seen from Fig. 2 (A and C) that by this procedure no improvemer.t whatsocver could be found. Thc discouraging conclusion seems unavoidable that no appropriate adjustment of the « nor­ma! range» in accordance with the systematic errors of the analytical proce­dure has taken piace.

Ann. Z.t. Supe1' . Sanit& (1971) 7 293-21111

ELDIARN E STIIOMME 297

When we recalculated the results r eported for the enzymes in first test serum, using the r esults from the second serum as reference st andard, a striking improvement was seen (Fig. 2, A and B). On thc average, for ali the enzyme assays, the coeffident of variation decreased from 38 to 16 %·

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Fig. 2. - Frequency hiatograms for the activit ies of foW' ensymes in one of t he two test sera (testserum A), analyzed with the most commonly used methods. The results are plotted as percent of the mean (the arrows).

lO

A : Tbe reported results (U(I). B : The reported rcsult s recalculated using as reference (= 100 percent) the corresponding activities, determined simulta· neousl y in serum B. C : The reported results recalculated using as reference ( = 100 percent) the u pper normallimit as stated by tbe respect ive laboratorie&•

(R eproduced with permission from Scand. ] . Clin . Lab. Inveii. (1) .

A nn. lat. Sut~er. Sa nìtà (1971) 7, 20S-2.9Q

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298 STANDAROJZZAZ IONE 1:: CONTilOLLO 01 Ql'ALIT.\

The improvement was least apparent for GPT, possibly nue to the fact that low aetivities were present in thr• t est sera. But cven in thi l" case tbc averagc coefficient of variation decreased from 45 to 29 %· These findjngs clearly show that systematic errors make up fo r tbc grcatl'r part of the variation in tbc reported valucs fvr enzyme activities.

Tbc bas ic and usually advocated rcmcdy to improvc tbc rcsnlts ,,[ cnzyme dcterminations is to uniform tbc mctbods uscd by tbc variou;. laboratones. As it was shown, our gruuping of results according Lo tbc methods did not improve tbe results sufficiently. Most probably, thc m e­thods claimed to ho uscd wcre not followed exactly. Smaller , mof! tly unnoltced modjfìcations of the originai m cthods bave b een int roduced; c .. ~ .

concentration of suhstrate, quality of r eagents, timo of incuhation, pJl . s trcngth of the buffer, amount of serum uscd, and in particular, incuhation temperature. Wc fear that it will prvvc extremely difficult to av oid such minor m<•difications wbich, in thc case of enzymcs, may cause grea t variationl'.

In <Jur opiniun the only practical way to impruve thc enzyme results would b e lo agrec upon the use of one cnzyme solution as refercncc slan­dard, against wbich the various cnzymc methods should be calihrated. Thc results presented here mdicate tbat such an approach would soon lead to appreciable accuracy and precision for a number of enzymes.

ConclusÌOtl

In conclusion wc want lo emphasize the following: The main purpost· <·f intcrlaboratory surveys on a national or international basis is to p rovidc a documentation of tbc routinc J>erformance <Jf the clinical laboratoric as a group. In our opinion these schcmcs shOtùd b e undertaken severa! timt'!' a year, and be prescnted to the bcspital owners and to tbc socicty. The snrveys sbould be carried oul, h owever, <'n a professional basis, and thc interfcren cc by commerciai fums or by tbc socie ty in establishing this typt· of contro! should be avoidcd and considered unnecessary .

Interlaboratory surveys may b e of some help in establishing tbc local, daily quality contro! schemc. Intcrlaboratory controls bave also becu proposed as a mean to establish « average analytical values » for refercnce standard sera. However, it may prove dangerous to b elieve that an average value straight a·way is thc true valuc.

Stmtmary. - The quality contro! p rogram that has becn opcrating in Norway during tbc last 5- 10 y ears is describcd. Tbc program has b cen working al threc different levcls. Tbc firs t leve] is thc daily control schemc within tbc individuai laboratory; this is uf paramount importance. The

A 1111. lat. Sup eT. Sanità (1971) 7, ~209

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ELDIARN E ST!IOM ME 299

second level centers around the laboratories of th e larger hospitals, and includes frequent screening of laboratory work on a regional basis. The third level is that of intemational, i. e. inter-Scandinavian surveys, that are regularly carried out since 1968.

Statistica! analysis of survey results has shown steady improvement, with reduction of analyt1cal errors. Results are still highly unsatisfactory in the fìeld of enzymatic analysis: this is due to lack of primary standards, and to the multiplicity of analytical methods. Regular use of enzyme reference solutions, as soon as they will be availahle, is likely to bring about improved results.

Riassunto (Controllo di qualità nei laboratori clinici scandinavi). - Viene descritto il programma per il controllo di qualità che è stato attuato in Norvegia negli ultimi 5- 10 anni. Il programma è stato impostato a tre diversi livelli. Il primo livello è rappresentato dallo schema di controllo giornaliero all'interno dei singoli laboratori; questo è di importanza fondamentale. Il secondo livello riguarda i laboratori dei maggiori ospedali, e comprende un frequente vaglio del lavoro dei laboratori su scala regionale. Il terzo livello consiste in controlli fra i paesi scandinavi, controlli che vengono attuati regolarmente dal 1968.

Un'analisi statistica dei risultati ottenuti ha dimostrato un costante miglioramento, ed una diminuzione degli errori analitici. I risultati sono ancora tutt 'altro che soddisfacenti nel campo delle analisi enzimatiche: questo è dovuto alla mancanza di standard primari e alle molteplicità dei metodi analitici. È probabile che un miglioramento dei risultati potrà deri­vare dal r egolare uso di soluzioni enzimatiche di riferimento, non appena queste saranno disponibili.

REFERENCES

( 1) STR0MME , J . H., S. CuR. S omu:RFELT& L. E LDJARN. Ann. Clin. Bwchem. , 6, 134 (1969).

(!) S TR0MME, J . H. & L. E LDJARN. Scand. ] . Clin . Lab. Invesl. , 25, 214 (1970).

(3) TONX:S, D. B. Clin . Chem., 9, 217 (1963).

A. nn. lst. Suver. Sani t~ (1971) 7, 20s-2gg

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A regional program of quality control for the clinica} laboratories in Helsinki. Results of the first two years.

A. HYVARINE~ (*)

Department of Clinica/ Chemist n ·. [ 'niversity ()J flpf5in ki. Finland

lu October 1966 a cooperative group of clinica! laboratories was esta· blished in Helsinki, aiming to encourage standardization of methods and to improve tbc quality of clinica} chemical analyses. The quality contro! system used was developed as one of the activities of tbc Fiwlish Society for Clinical Chemistry and Physiology (1).

The present study was made about two years after the · s tart of thr program, to evaluate th e performance of the participating laboratories in tbc period from October 1966 to Decembcr 1968.

Materials and methods

The participants to tbc control program are 9 laboratorics of thc H el­sinki University Centrai Hospital, 5 laboratories of the city hospitals, 4 cli­nica! laboratories connected with the State, the University aud the l'ia tio­nal Pensions lns titute, an d o ne large private clinica] laboratory. Ali 19 laho­ratories taking part to this program (recently 3 other laboratories bave joi.ned) should r epresenl tbc hest, rather tban the averagc, profeMional leve) in Helsinki; in chargc of all of tbem ar e graduate spccialists.

Briefly , in this quality contro! syst em a s ingle serum pool is analyzNI daily in routine work by ali laboratories, and tbc r esults are compared .

A frozen serum pool of left-over specimens of buman scrum is used: each batch lasts for periods of up to 6 montbs. Some of tb c participatin f.( laboratories coUect tbc sera required for tbe serurn pool. while a pharmaceu­tical company distributes the serum into lO ml tubes and delivers it frozell to users.

Because of iodinc contamination in tbe serum pool, we u e frceze-dri t>d human contro! serum M:onitrol (**) for tbc assay of PBI. Tbis contro!

(•) Present nddress: Ethiopian Nutrition l nstitute, P. O. Box 1768, Addis Ahebn. Et.biopia.

( .. ) Dade R eagents l nc. ~liami, Florida.

.• ""· lst. Suvor. Sanit4 (1971) 7, 300-318

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HHARI:oiDi 301

serum was also used in ali test s fora short trial pcriod. As shown in Tahle l, ali analytical values are within normal limits. At the beginning of the program, a pool of frozen bovine serum was used as the contro! serum for t hree months; this, however, was found impractical, hecause the levels of severa! constituents were quite different from the normal human levels (high K , high inorganic P, low cholesterol).

As shown in Fig. l , four entities cooperate in the Finnish contro! system: the group of the participating lahoratories, a Contro! Committee (*), a com-

PHARMACEUTICAL COMPANY

Finn ish Soc,ety f or Clinical Chemistry ond Physiology CONTROL COMMITTEE

LABORATORIES COMPUTER CENTRE

Fig. l - Schematic outline of the intcrlaboratory quality contro! systcm adopted in the clinica! laboratoriea of H elsinki.

puter center (**), and a pharmaceutical company ( .. *). The centrai unit consista of a 4-member Contro! Committee wluch plans, develops, and leads the contro! system. The participating lahoratories use the contro} sample every day for up to 40 different t ests (mainly chemical), according to the individuai routine and to the practical needs of each labo.ratory.

Twice a month the participants send their results to the Committee, which revises them and sends them to the computer center , whe.re the data are punched and processed with automatic data machines. A summary

(•) Dnring 1966-70 the membere of the Control Committee have been: A. Hyviirinen (chairman), N.-E. Saris, E. Leskinen, S. Niirvilnen (to 1968) and A. Louhivuori (from 1968).

(**) Oy Nokia Ab Electronics, Helsinki. (•••) Orion Oy, Helsinki.

.4. nn. 18t. SupeT. Sani t() (1971) 7, 3()()..3Ul

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oent

.

l•) Codlici

mt

of

dail

y n

riati

nn

w

itbl

n·la

bora

tory

, ea

lcul

aled

mo

~>th

ly

(aee

tu

t).

cl)

Dif

l'ere

nee

betw

een

the

qb

eo

t an

d lo

'"'o

t m

ean

>•a.l

ueo

of e

acb

IZIOD

lb,

•) H

ange

or

clio

trib

utio

n l

imit

o u

tim

ated

1ta

thti

eoll

y lO

ior

Jude

a t

lea.o

t 9

5%

o(

teot

val

oe•

io e

ach

labo

roto

ry (

"'e

Fig

. 3

anrl

tu

t).

•) E~

cluc

linr

; tb

e 6

nt

2 m

onlh

o (b

ovin

e au

um

wil

b a

bnor

mal

val

uH).

••

) E

IC!u

din&

l m

on

thly

ree

ord

of

l la

bora

tory

wit

b u

eep

tio

nal

ly q

b l

'c (

41,8

%) .

w

o N>

~

> z ~

:::;

s N

N ... N o z M "' g ~ 5 r b ;::

o c > c ;!.

--

--

---

---

---

---

---

---

---

---

---

---

---

---

---

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---

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---

----

--

--

----

---

---

---

--

---

-

HYVA.RINEN 303

sheet is prepared once a month for each substance; after approva! by the Committee, the monthly sheets are sent to ali participating lahoratories. Each participant evaluates his own performance: so far, the Committee has sent neither recommendations nor reference values to the lahoratoriee. The daily control values serve to each participant as instant check for the day's work. The lahoratories pay for the expenses that are met in the program. o l •

In Fig. 2, we show the glucose sheet for May 1969, as an example of t hese monthly summary reports. The sheet contains the results of the whole group of lahoratories; each laboratory is marked with a « secrct» code number. The monthly summary shows the analytical method, the average

PIBWISH SOC. ot MONTHLY AnalyBiBI 15 GLUCOSE CLII.CHEM.&PHYSIOL. STATISTICS HELSINKI CONTROL SYSTEM Run : 17.07. 69 Sample 1 A 07 Month1 5/69

R LAB METHOD UNITS PACTOR MEAJI or1g.un1t•

sì

o()

11

Hl

1ij

28

Fig. 2 - Summ.ary sheet of the quality cont.rol data for glucose (May 1969). beadioga bave been translated into Engliah.

Ve l

Only

8

12

14

18

10

20

22

24

28

tbe

va lue, the coeflìcient of variation V0 and the numher of teste N for each lahoratory for May 1969. If the concentratione are expreesed in unite other than st andard, this is stated in the sheet, and we report the average value in these units along with the factor used to convert them t o standard units. lf this conversion cannot h e done, the average value is stated only in originai unita and is not included in the calculation C>f the genera! mean. Alternatively, lahoratory results may be handled as separate subgroups.

A nn. h t. Sup er. Sanit~ (19'71) 7, 300418

l l l l l l l l l l l l l l l l l l l l l l l l l l l l l

STANUAillllZUZIONE ~ WNIRIILI.O m QUAl, l1 l

In the two hottom linet- \1 e sl•o"· tbc data from aU thc laboratories. obtained b y poohng ali iodh·idual tcEt rcsuJts or the laboratory m ean valucs.

Results and discussion (*)

As shown in Fig 2 for glucosc. daily results. avcrage valuc, and sca"tter are usua.lly different in the different laboratories. Io column Ve wc S<-'~'

tlaat tbc within-laboratory variation cocffirjcnts mny diifer sign ificantly

r

o

----7

Test value

Maximum allowable r ange or error

Lab.1

Lab.3

x-, x2 x3 ~------------------------ a ------------------~

~---------------- b -----~-~

Fig. 3 - Schema tic ouùinc to illu~ tratc st:nti;.t icul n~s1·ssmcut of rcsuhs (singlr coutponcut analyzed in three dilfcrrul laboratori<•,). \\ l' r eJ>Orl Lhr, gaussiun distributitJil curves of re~ults for Laboratorie,o L 2, and 3. wilh mcan vnlues X and >landanl deviations S . « a» is t hç r::tnge of thc mcan valt:e~. and « b» is tbc est imateli range of individ:ual t csl rçsults (di.triLulion limits). Maxim um allownhlr ranl!e of error is sho~,l for compurison . Se c n l so t ex t.

onc from thc othcr and from the variation coefficient for the entirt• grouJ•· Thc individuai variation cocflìcients cbangc Yery murh from monlh Lo

mooth, but tbc mcan values are fairJ y stnble. TabJc l presents thc rangrs of moothJy s tatistica) data for the whok period 1966- 1968.

Fig. 3 is a schcmatic drawiog intendt•d to clarify some of the statistica! param eters uscù in trus stuùy . When a sioglc serum pool is analyzed daily

(•) For tbc bn~ic principle.• of statistical methodology see r ef. (1); for 1:hr principle~ of 'luality control in cliuicaJ chemicnl nnalysis see rtf. (3 ) •

..t 1111. ht. Suucr. Sanitd (1971) 7, s oo-Sl3

HV\'ARINEN 30S

by a group of laboratories the test values X obtained will be dis trihuted in cach laboratory within a certain range bccause of technical errors; this range is defìned statistically by the average value X and by tbc within-laboratory day-to-day s tandard deviations, or the coefficient of variation Ve. Wc may es timate S and V0 as follows :

s =l/ ~(x- x)~ N - l

Ye = 100 s x

[l]

[2]

Fig. 3 shows the « normal» distribution curves ( l , 2 anù 3) calctùatell l'rom the test results of three different lahoratories. The pooled test values do not reprcsent a homogenous materia): rather, they show a mtùti-modal type of distrihution; as a consequence the abovc formtÙa for the calctÙation of S does not apply. Later studies by the autbor (to be puhlisbed) show that evcn within a single lahoratory the distribution of test valucs is oftcn ,-ariable with time and not nccessarily norma}; but this does not seriously affect tbe parameters considered here.

lf we compare the test results obtained in the different laboratories, l, 2 and 3, we may distinguish the range of average values xl, x2 and x, (range« a»), which depends only on the scatter of mean v alnes of the labo­ratories, aod the estimated range of individuai test rcstÙts (range «h»), which gives the overall spr ead of r cstÙts, and depcnds also on within-labora­tory variation.

To calctÙate the range « b» for each suhstance, we estimate tbe monthJy average X and the variation coefficient V0 for each laboratory us well as the 95 % one-tailed statistica! diRtr ibution limits , that is, the maximmn and minimum distrihution Jjrnits (see also)):

X v • . x

± t· !OO- (31

Ncxt, we single out the bighe t anù thc lowest limit in the whole group of laboratorjes, to dcfine range «h», which therefore r cprescnts the ùistri­bution limita of daily reswts, covering at least 95 % of the rcswts from eacb laboratory.

W e ha ve includcd in the fina! evaluation only the following l 7 suhstances: Na, K, Cl, C02 , s tanùard btcarbonate, crcatinine, urea-~, total proteina, glucose, Ca, inorganie P , cbolestcrol, triglyceriùes, uric acid, }i' e,

.dnn. ht. SupeT. San1tA H971l 7, 300-SIS

306 !-,LANIIAIII11/7.A/.I UM . L t:ONlltOI, W DI (JI1Af .l1 1

TlBC aud PBI. lr1 thcsc t cs ts we fou11d no cvidencc for dcterioration of thc control spccùnens with tjmc (up to 6 montbs) duriug thc entirc stud) . "\Vr lcft out em:ymatic actiYities aucl hiJi-ruhin, bccause we were nol qu.it e sun~ of tbcir s tability.

lnter/aboratory d~fferetzc<'S

Tahlcs l aud 2 ancl thc diagrams in F'ig. 4 sLow the esLimated muntWy rangcs « a» and « h» for all test !! in this s tudy . If the crrors are cvaluatcd al' pcrcentagcs of thc mca:;ureò quautity (Tallle 2, columns 2-3 and 6-7, and Fig. 4, lcft sidc), thc grcatest variatiuns are thos(· of scrum iron, where tbc· range of m enu valucs is 38 %, and thc 1'Catl cr of ali daily test result ,;

RANGE OF DIFFERENCES

N a

K Cl

co2 Stand. bicarb.

Creatinine

Urea-N

Protein

Glucose

Ca

P, inorganic

Cholesterol

Triglycerides 114

Urlc ac td

Fe

TIBC PB I

50 100 0/o of measured value % ot normal range

Fìg. 4- Hangcs of difl"erences fouud for annlyticru reJ>uh~ obtained in differcnl laboratoriee during the period 1966 to 1961!, and calculated us perccnLngf' of lhc mensured vruuc (left side) and of t.he eorresponding normiÙ human range (rìght bide). Dark 11hafts r eprcseut rauges of monthl-y mran values, white shafl~ cstìmated rangrs of dnily t est resnlls (d.istribuLion limi ts); botb are shown a~ the average for tlte whole contro! pcriod, lhe arrows indicating monthl)• variat iou. Droken liues show the ma.ximum nllowablc limit s of error calculatcd accordìng t o Tonks (sci' text and Table 2).

is 65 % on the average; next are the variations of creatininc, TIBC, trigly­ceridcs, uric acid, choleslero1, and glucose. These tests frequenùy exceedcd thc 20 % rangc (i. e. ± 10 %) formerly recommended b y Tonks (') as

A nn. lsL. Supcr. S~tn(t4 (1971) 7. 3ro-S18

;..

;:s ?' ~ ~ "' ~ :'

«>

p ;! s ;::: ,., :i

:-o "" ~ <O

TA

BL

E 2

lnte

rlab

orat

ory

anal

ytic

al d

iffe

reoc

es

foun

d io

an

alys

es o

o th

e co

otro

l se

rum

, an

d e

xpre

ssed

as

pe

rceo

tage

of

the

mea

sure

d av

erag

e va

lue

aod

of

the

oorm

al h

um

an r

ange

. S

ee T

able

l.

--

--

AN

Al.

YS

IS

R,u

'(c.t

: O

F

M€

AN

V

AL

tJE

S

l 1-

-:sT

UI.A

.'reo

&

A.N

GE

O

.V

DA

ILY

ll

ES

VL

T8

(dio

trib

utio

o li

mit

o)

--

~~ oC

mru

ure

d va

lu~

l %

of

noro

ual

rao

ge

% o

f m

eatu

red

val

uc.

l %

or n

orm

al

r&n&

e

Av

rrag

è l

Lim

ils

Avc

rage

l

Lim

iti

l A

ver

age

l L

imiu

A

ver a

go

l L

imit

i

N a

4.7

2.

5-6

51

27-6

7 11

7-

18

118

75-

192

K

9.3

7-

16

23

17-4

0 18

13

-2-l

46

32

-61

Cl

6.5

5-9

57

42-7

5 13

10

-19

11

4

86

-167

C

0 1

4.1

0.5

-9

lO

1-21

17

9-

27

41

22-6

7 S

tan

d.

bica

rb.

3.2

0

.4-6

20

2.

5-35

14

1{

}-.22

90

65

-135

C

reat

inin

e 24

14

-49

48

28-9

8 45

29

-97

90

58

-195

U

rea-

N

9.0

2-

16

22

5-41

27

17

-34

69

44-8

6 P

rote

in

l Glu

cose

9.3

6-

16

32

19-5

4 18

11

-26

62

38-9

0

19

11-2

9 60

33

-91

37

27-5

6 11

5 8

5-1

73

l

Ca

8.5

6-1

7 41

27

-81

18

11-4

0 90

54

-193

P

, in

org.

15

ll

-25

37

27-5

9 36

21

-61

87

49-

145

Cbo

lest

erol

19

9-

31

47

22-7

7 35

18

-59

86

43-1

45

Tri

glyc

erid

es

21

11-2

8 34

18

-46

35

18-6

8 58

3{

}-.11

3

Uri

c ac

id

17

11-2

0 21

14

-25

58

24-1

14

74

30-1

46

Fe

38

13-

50

40

13-5

3 65

47

-95

69

49-1

01

TIB

C

18

2.3-

43

37

5-88

45

27

-79

93

57-1

64

PB

I 5

.4

0.8

-10

8.5

1.

2-1

6 18

8-

32

29

13-5

0 -

l A

ver

age

of

ali

test

s 14

l

35

l 30

l

78

:t

~ .., >· :;

~

,.; "' .....

o ~

301! ::iT.\~11.\11111//~ZIONL E CONTRO! Ul 111 Ql' ALJT\

maximum allowable limit of variatiou. Tlw more con'>Ì'-l <.'nt r c::-ult l> an· tho~c of s tandard bicarLonatc·, 1\a. and Cl, with variatiou, as lo'' U'- :L~-

6. 5 ':o for th<· average 'alucs , aml of onJ~· Il 14 •;o for thc· O\'Crull M'a t tPr of rcsult~. 1'hc avcragc rangcs for aJJ test;, wc~ re l 4 o/.. for thc· mcau valuc;.. and 30 '% for thc estimntrd rangc of tb c dail y n ·sults.

Thc at·curary and pn•ci.,ion requireù for n clinicaJ chcmit'al lt' •l mu·t t akt- into account th<' norma) human range. Thercforc, in the ri~bt half uf rig. 4 uucl columns 4·5 ancl S-~ uf Tahlc 2, ali test .results are Nh 0\\'11 a, per ceni. of tbc gencrally acccpt rd oormal humnn rangc.

Th P rangcs of mcan values are sbown ab shadecl shaftb iu tht• righ t half of Fig. 4: tbc widest. nrr thosc of glucosc analysis (60 °<, of th<· normal rang<\). Ot.hcr t csts s bowing a range around 50~0 of the normal rangt· are Cl , l\a, crcatinint•. nnd cholestcrol. Thr narrowe$l ~.ocnttt· r ia fouml for PHT (onJy 8,5 °·0 in the nveragc) nnd for .K (23 ° 0 ) . ~h·an val ne~ anJ intcrlaborntory differenccs werc fouud to be fairl y stable, with rcla ti' d~ minor chauges from month to montl1.

Tbc estimatcd rangP of indi , -idual t est rcsuhs (shown a~ whit<' f' haft -. in tbc right half of Fig. 4) is \VÌÙer for :N a, glucosc, and Cl, gcnera lly t•xceed· iog tbc norma) human range (l )4- ll8 ° 0 ) . l t is nearl~ ns "iclc a;: tb c· normal rangr (86-93 %) for TIBC, crcatinint', s t andarù bicarbonatt• (~B) . Ca, P, and cbolesteroL

Tbc lowest scattcr of rcsults i s found for PHT (onJy 29 ~ o of th<' norma! raoge in th<· avcrage), uncl for K (46 %). T h<· nvcragc rangcs for nll test.~

wcrc 35 % of norma] rau g<• for tht mcan valuc11, and 78 % of normul rangt• for thc estimatcd rang<• of rcsuJt:-.

Tbese data show that a ltltough te&t~ :.m·h as Xa and Cl han th•· lowc&t errors in relation to thc measured qunntity, they art• tbc mu<~ l 'aria· ble with rcfcrcnce to thc normal human raug1·. Tbc data also show tlwt tht· prescnt t cdmique for scrum iron is inadcqunt r; obYiously tbc ùdìnitiou of' serum iron norma! rangc calls for furthcr s tucly.

A cceptability of test results

Tbc estima t ed rnngc~.o bave h eco uscd t o as:.css th<· \\ ork quulity uf tlw participating 19 laboratorit•s by thc well-knClwn formula of Tonks {4

) :

l /4 normal rangt· Maximum allowablc dcviation 11 ~ = 100 · [4)

normal average valul'

Tbis mcans that thc 95 % rangc of t e l rcstÙts (X ± 2 s) ~> htould not excccd 1/2 thc normaJ raoge, and that tbc coeffi cient of variaLion Y0 should no t excecd 1/8 tbc normal rangc, expressed as pcrcent of norma! a vera gr .

Ann. Irt. Suoer. San1til (1971) 7, Soo-313

;..

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TA

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per

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age

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part

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b ac

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able

m

ontb

ly

reco

rd

clas

sifì

ed o

n

tbe

basi

s o

f m

ean

va

luei

j, w

itbi

u-la

bora

tory

var

iati

on c

oeff

icie

nts

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and

est

unat

ed r

ange

of

dail

y re

sult

s (s

tati

stic

a) d

istr

ibut

ion

lim

its)

. S

ee t

ext

aud

Tab

le l

. -

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ge

ve

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cce p

t.

%

%

~' %

N a

...

...

...

. n

un

oli l

()

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l. l

(5)-

15

95

5 53

43

33

K

•

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4

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(5)-

15

100

o 96

l

92

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92

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.

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75

5.8

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98

2

63

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41

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I ....

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o 96

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l 54

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a o

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ora

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Co

r ea

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on

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%

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61

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47

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l 35

37

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45

25

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~' "" z ~ ~

'Cl

310 S'I'ANLIAIILII ZZAZ!ONI; E CO:<TROLLO DI QUAl-ITÀ

Furthcr adjustments of the m axim um value, as recommcnded by Tonks were not applied bere.

As shown in Table 3, in this s tud y onJy th(· PBI t csts bave constaotly met the standard requircment set by Tonks. A possihle explanaliou is that only a few laboratories (not more than 5) did th.is analysis, and tha L most of them used the same automated m ethod . Thc good results obtaincJ. for K, which is one of the tcsts more widely performed in this stud y (up to 15 laboratories), are more convincing. In the case of K assays, tbc overall scatter of daily test results was within acceptablc J,mits for tiH'

whole p eriod, and only occaswnally was the maXllDum allowahle rangc slightly ex ceedcd. The other t est, except perhaps serum hicarhonat c which was m easured in too few cases, are unsalisfaclory jf wc take into account the overall scatter of results. On thc olher hand, the levels of monthl y averagc values are always satisfactory f&r urea-~, triglycerides, s tandarù bicarbonate and C02 , in addition tu PBl and K. Except for K, however, thcse assays were clone only b y a small numbcr of laboratories.

Fig. 5 we mav now evaluatc the work quality of individua] 1abora­tories1 and see how many of them ubtain.t?J acceptable results . Table 3,

N a K

Cl

co2 58 Crea t . Urea-N

Protein

Glucose

Ca

P, inorg. Cholest. Triglyc.

Uric ac.

Fe

TIBC PBI

Mean values Within-lab. Ve Dtstr. limits F ig. 5 - Aver age pcrccnta­ge of laboratorics gtv:mg acceptablc r esults(dark sl:tafts) und unacceptablc reeults (white bha­ft s) classifieol ou thC' basìs of annly­tical r csults ohtni­nrcl for the coutrol scr.um during tbe eutirc pcriod. ln the first column. wc based our estimate on the mouthly mean values; ÌJl th<: secon<l column, ou the with.in·labora­tory variatiou cocf­ficients; an<l in thr. tlurd column, on thr estimateci rangc of daily test vaJues (distributioo limits). Sce text.

and Fig. 5 bave b een prepared on the basis of ali monthly summary sheets: they show the percentage of laboratories that obtained acceptable (dark shafts) or unacceptable (white shafts) results in the different tests

A n11. T st. Super. Sanità (1971) 7, 3()0...313

HYVARJNEN 311

on the average during be whole period (not necessarily same laboratories 'rom. month to month). We did this fìrst by Iooking at the within-laboratory variation (V0 ); second, by considering the scatter of average results (that is, tbc interlaboratory ùiffercnces); and third, by looking at the overall scatter of the daily test results (distribution limits). For the latter estimate we calculated tbc maximum allowahle error for each batch of contro! .serum on the basis of scatter around the generai mean. At present this calculation though open to criticism, appears to be the best compromise afl it keeps tbc number of unacceptable results as low as possible.

As shown in the las t line of Table 3, the average percentage of accept· able results for the whole period and all test is high (98 %) if wc consider the me an rcsults an d i t is lowcst ( only 54 %) if we consider the ovcrall scatter cf daily test resuJts.

If we look a t Table 3 in more detail wc see that, though acceptability is high for the m can values (92-100 %), we sometimcs find unacceptahle valut~S for glucose, Cl, and Na. For most snbstanccs acceptahility becomes much lowe·r if we consider day-to-day variahility; with this parameter the loWt!St percen tages of acceptable results (27-63 %) are found for standard bicarbonatc, ~a, Cl, triglyceridcs, and TIBC. If thcse two sources of error are ndded together - as happcns whcn we consider the cstimated range of results of all laboratorics -wc find a low degree of acceptability; the lowest values are 23 % (averagc) for Cl, 27 % for standard hicarbonate, and 33% for glucose, triglyccrides, and N a. The highest percentage of acceptablc results is found for PBI t94 %) and for K (92 %): thcse are the only satisfac­tory tests fuund in this s tudy.

The parumeters m cntionetl in this paper vuried generaUy from month to month . Many of thcm, howcver , showed a definite trend toward lmpro­vcmcnt; this mjght be interpret ecl as a progress brought about by tbc contro! '>ystem.

Conclusions

Summing up our results, we d.raw the folluwing conclusions. l) If wc usc the norrnal human range as refercnce, we fintl tbat

on ly the results of PBI and K analysPs ar e sutisfactory . 2) Thc average valuc d daily rcsults obtained in each luboratory

is fairly s table. In 98 % of the cases the interla boratory scat ter of mcan values ùoes not excccd t he maximum allowahlc limits of crror; glucose is an cxception.

3) On the other haod, tbc ovcrall scatter of tlaily test resuhs greatly exceeds the allowahlo limits of crror. The scatter of daily test rcstùts of ali laboratories was, in tbc average, about equal to the oormal range for 9 suhs tances; otùy 54 % of all rcsults wcre withio allowable limtts of error .

.l nn. l 4t. Suoer. S11nitd (1971) 7, 300-31~

31:! STANDARDIZZAZIONE E CONTilOLLO DI QUALITÀ

4) Tbc• most un satisfactor y of ali 17 assays wcre those of chloridc, l'Odium, and glucosc. Thc assays of chloride and sodium werc thn leas t Yar iahlc• when cxpresscd as pcrcent of tbc measured value, but they were quite imprecise when the normaJ r ange was takcn as refercnce. Tbc assay of ~lucose scemecl t o be not only imprecise but a lso inaccurate, b C'causc of ..-ystematic errors in the test results.

Wc clid no sp ccific study on the accuracy of analytical rcsults becaUS(', uufortunatcly, contro) sera giving « true» analytical refcrence values were not available, as they are no t today: thercfore, wc wcrc ahlc to assess accuraC) only in terms of agrcemcnt h etwecn averugc results fr(lm different laboru· tories. Such an estimate, of coursc, is op cn to criticism, and many possihlc· <·rrors roay go uudetected.

Our results, like tho~e disclosed in many previous reports, demons tratc tlw urgent nccd for highcr standards of p erformances in clinica! chemistry; thcy are somewh at discouraging, if wc considcr that thc sample analyzcd was a known contro) serum, and that most participating Jaboratories werP ratcd among the hcst in H els inki.

In this paper I gavc only an ()verall picture of tbe errors occurrin~ in tbc clini~:al chemicul labora tory; more spccific studies are undrr way all(l wùl hP reported cbcwhcre.

Suuunary. - A regional quality contro! system is descrihed, to which J 9 clinica) chemical laboratorics of H elsinki participated. Monthly stati­stics, elabora ted by a computer center, notify the partccipants of the results obtuined in a li tbc laboratories , in ordcr to cvaluatc tbc rcsults of each laboratory.

Th<' results obtaincd during the first two years of expcrimentation (Octobcr 1966-December 1968) are discusscJ . During this pcriod tbc same fro:ten pool of sera was uscd as a daily control sample. The main source .of crror wall the high« within Jahorat ory» variability. Only thc aualyses of K and PBI gave fairly satisfactory results; tbe measurements of Na, Cl and glu('OSC were thc lcast satisfactory among the 17 t ests considcred.

Riassunto (Programma regionale di controllo eli qualità nei laboratori ('liniri di Helsinki. Risulati ottenuti nei primi due anni). -Viene d escritto un sistema regionale di controllo di qualità seguito da 19 laboratori chimico-('linici di Helsinki. Statistiche mensili elaborate da un Centro di calcolo dam1o noti~ia ai partecipanti dei risultati ottenuti in tutti i Iabora­ton, allo scopo di Yalutarc i r isultati ottenuti da ciascuno.

Sono discussi i r isultati ottenuti nel corso dci primi due anni di sp cri­mcntazione (ottobre 1966-dicemhre 1968) nei quali veniva utilizzata come

A nn. l$ t. Suvcr. Sani tèl (1971) 7, 300 ·313

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HH:\RINE:-1 313

campione di controllo giornaliero una stessa miscela congelata di sieri. La principale fonte di errore è stata l 'alta variabilità dei risultati ottenuti «entro i laboratori». Solo le analisi del potassio e dello iodio proteico hanno dato risultati abbastanza soddisfacenti, mentre i dosaggi del sodio, del cloro, del glucosio sono stati i meno soddisfacenti fra i 17 dosaggi considerati.

The author is indcbted to :.\lrs. Sheila l\fahlberg for her help in tbe translation in English of the manuscript.

This study wns supported by n grant from the research foundation of Orion Oy, H elsinki, Finlnnd.

REFE RENCES

(l) H YVARINEN, A. & N. E. SARI S. Scand. ]. Clin. Lab. lnvest., Suppl. , 110, 97 (1969).

(2

) :\IACK, C. Essentiab of stalistics fo r scientisu and technologisu. Plenum Press, New York, 1967.

(3

) BCTr::'IER, H. & D. STAMM. Z. Klin. Chem. Klin. Biochem., 4., 303 (1966).

(4

) ToNKS, D. B. Z. Anal. Chem., 24-3. 760 (1968).

A nn. lat. Su Der . Sanità (1971) 7, 300-313

Il

l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l

Quality control: its meanmg and importance for the

clinical chemist and its development m Australia

\'\'. RO)IA'>

The Qucen Victoria H uspit11l, Adelaide, Australia

Quali t y Contro! m cans the checking of regular routine chemical analyses. The term « quality control» implies som~ sort of metbod fo r recognising at an early s tage in a procedure variations greatcr than can Le expect ('(l frorn chance alone. Such m cthods h a ' e long b ecu u scd in industry and al so in analytical laboratories, whcre therr valuc is well r ecoguiscd. Quality control materia! should be material of a consistent and known composition which is analysed at tbc same time as a batch obtainr d i n any proùuction which req tires analysis . Quality contro! m ateria! is not necessarily, and should not be rcgarded as a s tandard. Its m ost importan t property sboulù b e its unvaricd composition. Thts is easily obtained in industry, whcr c­uniform materia} is u sually analysed. Tbc materia! with which wc bave to dr al in clinica! chcmistry is, howevcr, ra rely o t uniform com posi t io n, and it is also a colloidal solution contaming proteins and lipids (which a re not in proper solution), as well as ions and other solutes. Thcsc solutions arr essentially uns tablc. This is thc main difficulty wbich had to b e ovcr­comc before quality contro! could b t• introduced in clinica) chr mis try.

Io clinica! chcmistry wc are analysing ever larger Latchcs of materia! for tbc same chcmical components . It is of vital importance tba t a labora· tory will use metbods and techoiques wbich wìll givc repcatablc rcsults . lt is of course an advantage if tbc acctrracy of our r esults is high, bnt more importanl stili is the rcpcatability of our r esults . Quality contro! assurcs rep eatability, hut cannot en sure accuracy b ecause thc materia! can only b e as accurately analyscd as thc mctbods used a llow. Aqueous solutions bave been uscd as stanùards in clinica! chcmistry rigbt from tht• beginning. Many clinica! chemists r elatcd, and stili do r elatc, results of their unknown batches to a known standard in aqueous solutions ruo tbrough at tbc same time witb a ccr tain batch. lt givcs some assurance of tbc rcliahility of t be results obtaioed. Tbis applies, howcver, only for su eh substances for

A nn. h t. Suver. So.11ìtA (1971) 7, 814- S

l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l

RO:\lAN 315

which reliahle aqueous s tandarcls can be produced , e. g. the electrolytes or glucose. Aqueous solutions as s tanda.rds are not very suitahJe for the proteins, and of course, impossihle for cnzymes and some other parameters.

Ahout 12 years ago, we felt that aqueous solutions were not a sufficiently reliahle quality contro} materia!, though at that time some pure pro .eins were already availahle, and one could make s tandard solutions of, say, albumin. These were suitable as stanclards, but their keeping quality is not sufficient to make them useful as quality contro! materia!. Efforts bave been made by severallaboratories to prepare sera suitable for quality control. Deep-frozen aliquota of pooled serum ar e quite satisfactory for contro) analyses for elcctrolytes, urea, uric acid and cr eatinine t1), hut are tmsuitable in regard to suhstan~;es su ch as enzymes, proteins and glucose, wbich will deteriorate with time in the deep-&ozen state. On tbc other band, if serum is fr eeze-dried, ;t will keep in ampoules for a fairly long time, some cons tituents up to lO years (2), especiaUy if refrigerated.

In preparing qual:ty control materia! a large quantity of human serum must be pooled in order to jus tify the amount of work involvcd . An exact amount of the pooled serum, say lO ml is pipetted into each ampoule and freeze-dried immediately, then at least 15 of these ampoules are analysed in duplicate for each of the constituents for which one wants to ha ve quality control. The analyses should be carricd out on diflerent days so that allow­ance is made for day to day variations in temperature, humidity, etc.

From the rcsults of 30 analyses can be calculated a m ean and standard ù eviation which are s tatistically significant, and f10m these values a quality control chart similar to that given in Fig. l cnn be set up. This figure was ohtained many years ago, and has been discussed in detail in a previous paper ta) .

The csscntial features are the horizontal lin es representing the values of the m ean plus two s tandard deviations, the mean and the mean minus two standard dcviatioos. The range, m ean ± 2 standard dcviations, should include 95 % of ili results obtained in the lahoratory for this quality contro) materia!, ohtained by the particular analy tical m ethod in use, that is, only one result in 20 can b e cxpected to lie outs ide this range b y chance alone. Some prefer to use ± 3 standard deviations to allow also for uneven distribution of deviations from the mean. Then less than l % of all r csults ,;hould lic b y chance outside the contro) range. I think, ho'\\ ever, that thcse limits are too wide, a tHl chat results in the clinical laboratory should lie inside ± 2 s tandard deviations.

In the lnstitute of Medicai and Veterinary Science in Adelaide, we prepared some quality control serum at that time from human serum kindly provided by the Red Cross Society. This was used for some t ime in cvery batch of analyses carricù out, as shown in Fig. 1.

.4 nn. I st. Suver. Sanità (1971) 7, 81~20

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fig. l. - Contro! chart for hlood urea uitrogeu determinatiou~ (urea~e method: •ee text).

Human scrum cau , howcvcr , not be obtaineù from thc Red Cro~!' in suffidcntly large amount .;; lo prcpare qualit) contro! materia! fo r ali require· ments inùefin.itcly. It was thcn trieù to U "(" hon-e serum. Horse serum can b e obta.incd in a fa.irly la rge qunntity .. as one can get r easonablc amowtt:­of blood a t onc blecding from onc hor:;e. Horsc serum has. howewr, tlw disadvantage that sneral parcmetcrs are pre.:.ent in quitc diffcrcnt amount~ from tho:;e foWld in human serum Also, the protein:-. of thc borse are different from thosc of hnman~. Trial;. werc r un in cooperation with tht• Commonwealth Serum Laborator ies in Au tralia with hor:,c scrum wbich showcd up tbc e disad.,antage.s, but werc useful as preliminary cxperitncnt!' . Thcsc showcd th at frozcn scrum is definitely nol suitablc as a quality con tro! materia! as it cannot be kept long enough. On thc other band, JyophilizcJ scrum {frceze-dricd) introduce~ anothcr pos:;iblc error. lf the dispens ing mcthod of the lahoratory preparing the lyoph.ilized serum is not Ycr~ accurate, the rccons titutcd ser um will no t be c"actl) tbc sa w e e a eh timi'. Another point is t hat rccons titution has to be carried out vcry ca refuiJy. An accurate pipettc or small di spenser has to be u scd which deliwr thl· same amount of water lo each ampoulc cach lime. Th c mixing has aho to be carried out car cfull y and accuratcly. lt wa, found be.st t o carry out th.is mixing on a rotating turntahle al a uniform tcmpcra tur <' , which should also not Yary from day to day. In a "ay, this is anothcr quality contro!. b ecause it chccks t bc accuracy of the pipctt c used in thc particu lar laboratory.

.~ 1111. ltt. Suver. Sanità (1971) 7, 314-S!!O

l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l

HO~lAN 317

Sincc then, some commerciai fìrrus bave prcpar cd such lyophilized sera. In Australia, we did most expcriments with Versato}, pionccred and devclop­ed by Warner-Lambert, of Morris Plains in the U.S.A. Thc Aus tralian Association of Clinical Biochcmis ts was able to arrange for Versato! A to be supplied to its m cmbcrs at a reduced price. Thc discount was subsequently madc available for othcr products in thc Ver atol range. This indur<'ment rnaterially assistcd thc widcr adoption of thc principle of quality contro! with evcry batch of speciUtens though now other commerciai product s are also used by Australian laboratories.

In thc United Kingdom, Borroughs Wellcome & Co. producccl a suitablc quality contro! materia! which all mcmbers of thc Association of Climcal Chemists of thc Unitcd Kingdorn are now using .

• W thcsc sera ar e prepared from human Rcrum in large batches. Each batch varics slightly from the next, but each batch is accompanicd with a chart giving its composition. (These charts are supplied by the manufac­t urer ). Thc analy.si, is carried out by mcthods s tatcrl on the shee t by Borroughs W cllcome. W arner Lambert rclics lcss o n analysis of the complcted products t han o n di al ysis to remo ve ali the dialisable materia! frorn the serum hcfore preparation. The watcr soluble ;.ubstances a re then add('(l in weighccl-in amounts and then an analysis is carried out of the cornplcted mat<'rial. These commcrciaily preparcd quality contro! matcrials havc been uscd as standards by some laborntories by taking the figurcs givcn by thc manufaclurers at their facc value. This is not p crmissible for two reasons: fìrs t of ali, quality contro! malerials should not be u scd as s tandard, as onc cannot rely on the absolute fi gl.! res. Even with the materia! prepared hy weighing-in, onc cannot rcly on the absolutc valucs. Sccondly, the methods uscd by thc mamtfacturers may not be the same as thosc used in any particular laboratory which wants to usc thi s quality contro! matcrial. One can use it to measure the r~pcatability, but onc should not relatc one's fi gurcs to thosc obtained on tbe Cj ttality contro! material.

To obtain proper quality contro! limits, one ::;hould rcally analysc the c·ommcrcial materia! in the same way as on e would do onc's own material, a.s discussed abovc. Only then ran on e rcly on the contro! limits. Ncvet­thclcss, if one has a suitahl<' chart, r ecording only the commerciai quality rontrol matcrial run through with cach batch, onc can usc this to see whether thc batch is in contro!. This will show up Jrnmeclatdy any variation which shoulcl b e cxamincd h efore the rcsults g<' out.

l\1any organisations have run comparative surveys in which a large number of laboratorics have takcn part. E very clinical chemist knows that as onc looks at the rcsults of thesc surveyl', one is as toundcd and aghast :tt the largc variations from laboratory to lahoratory . The College of Pathologis ts of Aus tralia, in conj tmction wilh the Aus traliau Association

.4nn. Ts~. Suver . Sani tà (1971) 7, 31-1-~~0

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9.2

9

.0

9.5

9

.2

9.8

9

.6

9.6

9.

1-10

.5

B

10.2

10

.6 1

0.0

9.

2 10

.0 1

0.0

10.0

10

.2

9.5

9

.9

9.7

9.

8 9

.9

9.7

9.9

9

.2-

10.6

Chl

orid

e (m

Eqf

l)

. .

. .

. .

A

102

100

100

99

104

103

103

100

97

100

98

104

103

101

101

97-1

04

B

110

105

107

103

112

105

111

109

103

111

105

113

111

109

108

103

-113

Cho

lest

erol

(m

g/1

00 m

i)

. .

. A

27

5 22

2 22

5 18

0 21

4 20

5 20

8 20

0 22

9 21

9 22

0 26

0 32

2 20

8 22

8 18

0-32

2 B

26

0 21

9 20

0 17

9 20

2 19

5 19

1 18

5 24

8 21

0 23

0 24

5 30

6 19

9 21

9 17

9-30

6

Clu

cose

(m

g/1

00 m

i).

. .

. .

A

80

87

65

67

67

90

63

60

50

62

125

70

62

60

72

50-1

25

B

145

134

145

123

118

130

137

135

100

119

149

116

121

117

128

100-

149

Sodi

um (

mE

q/1

).

. .

. .

. .

A

140

142

142

144

142

140

143

140

135

138

140

143

141

141

141

135-

144

B

148

147

140

150

146

145

146

147

144

147

146

147

150

147

146

140-

150

Pot

asai

um (

mE

q/1)

.....

A

6.9

6.6

6.9

6.

4 6

.9

6.7

7.

1 6.

7 7

.2

6. J

6

.5

5.6

6.

9 6.

8 6

.7

5.6

-7.2

B

7.

5 6

.8

7.2

7

.0

7.3

7.

3 7

.0

6.7

7

.7

7.1

7.

1 6.

1 7

.6

7.5

7.

1 6

.1-7

.7

Phos

phor

us (

mg/

100

mi)

..

• A

6

.4

5.4

6.4

5.

8 6

.4

6.11

6

.4

6.5

4.6

6.

7 6

.2

7.2

6.3

6

.9

6.3

4

.6-7

.2

B

5.9

6

.2

6.1

5.

3 5

.8

5.9

5.8

5.

7 4

.9

5.8

5

.6

6.2

6

.1

6.4

5

.8

4.9

-6.4

Pro

teio

(g/

100

mi}

. .

. •

• .

A

6.7

7.

0 6

.8

6.4

7.

1 7

.0

7.1

6

.6

6.9

7

.0

6.8

7

.2

7.2

6.9

6

.9

6.4

-7.2

B

6

.4

7.0

6

.8

6.4

7

.2

7.2

7

.0

6.5

6.6

7

.0

6.8

7

.1

7.4

6

.9

6.9

6

.4-7

.2

Ure

a (m

g{lO

O m

i) •

..•.•

A

30

38

40

32

36

40

38

30

51

36

32

34

36

30

36

30-5

1 B

90

10

0 10

5 10

4 10

4 11

8 11

1 Il

O

116

108

102

103

106

107

106

90-

118

Uri

c ac

id (

mg/

100

mJ)

• .

.

. A

5

.9

4.4

-

5.6

5.0

5.

9 5

.2

5.6

6

.2

5.2

5

.8

4.6

5

.3

5.9

5

.4

4.4

-6.2

B

3

.9

3.2

-

3.9

3

.1

3.9

3

.7

3.8

4.2

3

.5

3.8

3.

2 3

.4

4.0

3

.7

3.1

-4.2

---·--

-----

6 2:

>

2 "" ..... "'

320 STANilAIIIJIZZAZIU:-\b C CUNl'fiO LT.O DJ QUALJT\

of Clinical Biochemist s ha~ been lUnning thPse surveys annually for almoi't t cn years now. The variations from onc laboratory to another wcre, in thc beginning, trcmcnùous. This , howrvcr, improvcd with th(· introdul'­tion of quality control. Tablc l gives a comparison bctween ali JabOla­tories and thosc who are using quaJit~· control. It shows quitr clearly that the vanatioos among the laborator ies using quality contro! are much less than thosc for ali laboratori es (aboul 90) taking part in this survey. Some of the large laboratorics which are using more uniform equipmcnt an d uniform metbods as well as f{Uali t y contro! gives rcsults which are, in mos t cases, very eluse to each other, with a far smaller spread , as shown in Tablc ~.

I hope to have shown tbc essential importancc and advantagr of using quality contro l in a clinica) laboratory. I ha ve also indicatcd the difliculties which bcsct the introduction of this control io the carly stagcs, which are now much lc~s with the availability of reliahle contro! materia! from com­merciai sourccs. To get full b cnefit of quality control, howcver, onc muH ncver forgctthat the occas ionai runniug-through of one contro! samplc will nc­vcr give a r eliabl .. indìcation. This can only b e achicvcd if the quality contro! materia} is run through with evcry batch analysed in thc day to day routinc.

Summary. - Thc basic chara cteri~tics of quality contro) are examined. Jt is shown how to perform quality contro) by the u~c of commerciai contro) sera an d of poolcd sera prcpared in the laboratory. Attention is cali ed t o th c fact that contro} sera shou ld not b e considercù :•s refercnce s tandard,.;.

Thc quality contro! program promotcd by th•· Australian A sociation of Oinical Biochemistry is briefl y illustratcù. Tbc author empha~izes that il is necessary to include a contro! snwplc in each analytical serie, .

Riassun to (Il controllo di qualità: il suo sign~fìcato c la sua importanza p er il chimico clinico e i suoi sviluppi irt Australia).- Vengono prel:ie in esame le caratteris tiche fondamentali del controllo di qualità, nonchè le modalita pratiche per il suo espletamento con l'impiego di s ieri di controllo commer­ciali, ovvero di miscele di s ieri preparati in laboratorio. Si richiama l'atten­zione sul fatto che, nel loro uso, i s ieri di controllo non devono essere cons i­derati come standard di riferimento.

Si sottol;uca l'esigenza di associar e un campione di materiale di controllo p er ogni serie analitica.

Viene illustrato brevemente il programma di controllo di qualità pro­m osso dall'Australian Association of Clini ca) Biochcmistry.

REFERE;\CES

(l) WALFORD, R. L., ~I. SOWA & D. DALEY. Am. ]. Clin. Patlwl. 26, 376, (1956). e> STRUMIA, l\1.1\I., J. J . .Mc GRAW,& G. E. HEGGESTAD. Am. J. Cl in. Pathol., 22,313 (1952). (3) RoltAN, W. Proc. Australian. Assoc. Clin. Biochem., l , 7, (1963).

A nn. bt. Suver. Sanitd (1971) 7, 314-32~