Clin. Biochem. 10, (3) 133-137 (1977)
The Use of In Vitro Diagnostic Kits in Hospital Laboratories in Canada J . E . L O G A N a n d D. R. T A A D A
Bureau of Clinical Chemistry and Hematology, Laboratory Centre for Disease Control, Health Protection Branch, Health and Welfare C a n a d a , O t t a w a , Ontario (Accepted
February
CLBIA, 1'0, (3) 133-137 (1977) Clin. Bioche~. Logan, J. E., and Taada, D. R.
Bureau of Clinical Chemistry and Hematology, Laboratory Centre for Disease Control, Health Protection Branch, Health and Welfare, Ottawa, Ontario K I A OL2 T H E USE OF IN VITRO DIAGNOSTIC KITS IN H O S P I T A L LABORATORIES IN CANADA 1. A survey conducted among hospital laboratories has yielded data from 640 institutions concerning the use of diagnostic kits and reagents in Canada. 2. Kits designed to test for chemical constituents were most frequently used in hospitals of 51 to 600 bed capacity whereas the ones for enzymes were most extensively used in 201 to 700 bed-size institutions. Kits based on the CPB principles were generally used in hospitals of more than 200 beds whereas those based on RIA were only in frequent use where the bed capacity was 351 or more. 3. The following tests were most often performed by kits': aminotransferases, amylase, urea, LDH, phosphatases, glucose, CPK, bilirubin, calcium, uric acid, T-4, T-3, digoxin and vitamin B12. 4. The survey reflects a continuing and increasing usage of in vitro diagnostic kits and associated blood analyzer systems. It also indicates a significant adoption of assay kits which utilize RIA and CPB principles.
7, 1 9 7 7 )
s u r a n c e p r o g r a m is provided. Two s u r v e y s on t h e e x t e n t of use of kits and a n a l y z e r s y s t e m s have been c a r r i e d out a n d r e p o r t e d ' ' ' ~ . The r e s u l t s of a t h i r d such s u r v e y conducted in September, 1975, are p r e s e n t e d here as u p d a t i n g i n f o r m a t i o n * .
MI~I~IOD A questionnaire was prepared and mailed to all 1387 hospitals in Canada. Hospitals were surveyed regardless of whether or not they possessed clinical laboratory facilities, and they were requested to reply even though no kits or associated analyzer systems were used. Hospital personnel were requested to indicate the bed capacity of their institutions and to t r y to estimate the total volume of tests per month performed by kits. Three check-off lists of tests were provided, for determination of 39 chemical constituents, 20 enzyme constituents, and 36 for constituents tested either by radioimmunoassay (RIA) or competitive protein-binding (CPB) techniques. This was the first time that the latter categories were included in a survey. In addition to checking whether a kit was used for the test, the name of the kit and its m a n u f a c t u r e r were requested and an indication of whether it was used on a routine or standby basis. For chemical and enzyme constituents the participants were asked to name the analyzer system used when the kit formed an integral part of such a system, e.g., Eskalab, Clinicard, Dupont ACA, etc. In the cases of RIA and CPB tests, the type of isotope used was requested. Systemsort punch cards were employed to record the information received from the completed questionnaires. RESULTS
THE IMPROVEMENT of the q u a l i t y of p e r f o r m a n c e of l a b o r a t o r y t e s t i n g in clinical c h e m i s t r y in C a n a d a has been a concern of the L a b o r a t o r y C e n t r e for Disease Control since 1952. M a n y e v a l u a t i o n s of in vitro d i a g n o s t i c kits a n d r e a g e n t sets available on the C a n a d i a n m a r k e t have been c a r r i e d out a n d r e f e r ences to most of the p u b l i s h e d r e p o r t s are c o n t a i n e d in the b i b l i o g r a p h y of a p r e v i o u s r e v i e w a r t i c l e " ' . More recently, the l a b o r a t o r y has been active i n t h e development a n d e s t a b l i s h m e n t of r e f e r e n c e m e t h o d s a n d m a t e r i a l s w h e r e b y the p e r f o r m a n c e of m e t h o d s in r o u t i n e use m a y be m o n i t o r e d . T h i s includes e v a l u a t i n g the p e r f o r m a n c e s of clinical c h e m i s t r y kits a n d associated blood c h e m i s t r y a n a l y z e r systems. Thus, i n f o r m a t i o n c o m p l e m e n t a r y to a g e n e r a l q u a l i t y as-
Replies to the s i n g l e m a i l i n g of the q u e s t i o n n a i r e were received f r o m 819 hospital l a b o r a t o r i e s . T h i s was c o n s i d e r e d to be quite a good response since it r e p r e s e n t e d a b o u t 59% of the total n u m b e r dist r i b u t e d . Of the 819 replies, 640 r e p o r t e d u s i n g one or more kits in t h e i r l a b o r a t o r i e s . A geographica] b r e a k d o w n of the replies of k i t u s e r s is shown i n Table 1. Table 2 shows t h e d i s t r i b u t i o n of all r e t u r n s to the q u e s t i o n n a i r e a n d the n u m b e r u s i n g kits categorized according to hospital size. F o r hospitals of 150bed c a p a c i t y or less, 431 r e p o r t e d u s i n g k i t s ; t h i s is 67.3% of the total, a h i g h e r p e r c e n t a g e t h a n t h a t f o u n d in 1968 '2). T h e p e r c e n t a g e of total l a b o r a t o r i e s u s i n g kits a c c o r d i n g to hospital sizes shown in T a b l e
Correspondence: Dr. J. E. Logan, Bureau of Clinical Chemistry & Hematology, Laboratory Centre for Disease Control, Tunney's Pasture, Ottawa, Ontario, K1A 0L2
*Presented in p a r t at the 20th A n n u a l CSCC Conference, Ottawa, July 13-16, 1976 - - see CIin. Bioche~n. 9: P6, #3 (1976).
134
LOGAN AND TAADA TABLE
capacity. I t is n o t k n o w n w h y the volume reported is less in the two categories m e n t i o n e d above. T h e n u m b e r of hospitals r e p o r t i n g in the l a t t e r case is only t h r e e and as such does n o t c o n s t i t u t e a good s t a t i s t i c a l sample. I n T a b l e 4, c o m p a r i s o n of the w e i g h t e d a v e r a g e s f r o m Table 2 is made w i t h those calculated f r o m data o b t a i n e d in our 1968 a n d 1971 s u r v e y s ' ' , ' ~ ' These data show a c o n t i n u i n g i n c r e a s e d use of kits with the a v e r a g e n u m b e r per hospital used for chemical c o n s t i t u e n t s exceeding t h a t for enzymes. The fact t h a t kits are available f o r a g r e a t e r v a r i e t y of chemical tests t h a n f o r enzyme tests coupled w i t h the knowledge t h a t the total l a b o r a t o r y workload for chemical tests would, in most laboratories, be cons i d e r a b l y g r e a t e r t h a n t h a t for enzyme tests c e r t a i n l y c o n t r i b u t e s to these s t a t i s t i c s . One could conclude f r o m these f a c t o r s t h a t use of kits for enzyme t e s t i n g m u s t c o n s t i t u t e a g r e a t e r p e r c e n t a g e of the total workload for enzyme a n a l y s e s t h a n in the corresponding s i t u a t i o n for chemical c o n s t i t u e n t s . Table 5 shows the n u m b e r of l a b o r a t o r i e s u s i n g kits for each of the chemical tests expressed as a perc e n t a g e of the total 640 l a b o r a t o r i e s u s i n g kits. K i t s were most f r e q u e n t l y used for t h e following tests (in d e s c e n d i n g o r d e r ) : urea n i t r o g e n , glucose, bilir u b i n , calcium, uric acid, cholesterol, t r i g l y c e r i d e s a n d phosphorus. A n e x a m i n a t i o n of the r a t i o of the n u m b e r of hospitals u s i n g a k i t for a p a r t i c u l a r c o n s t i t u e n t i n r e l a t i o n to the total n u m b e r of hospitals in t h a t size c a t e g o r y revealed s i g n i f i c a n t p a t t e r n s . The most f r e q u e n t use of kits for urea n i t r o g e n , glucose a n d b i l i r u b i n was f o u n d to be in the f i r s t t h r e e categories, i.e., small hospitals up to 150-bed capacity. F o r cholesterol, uric acid, calcium a n d phosphorus, more ext e n s i v e k i t use showed up in the 51-100 bed c a t e g o r y and decreased a g a i n a f t e r 350, 500, 600 a n d 700-bed capacities, respectively. F o r t r i g l y c e r i d e s , a s i g n i f i c a n t use of kits is n o t f o u n d u n t i l a 201-250 bed c a p a c i t y is reached a n d is t h e n c o n t i n u o u s up to 700 beds. Data are shown in Table 6 for the e x t e n t of use kits for enzyme d e t e r m i n a t i o n s . I t will be n o t e d t h a t
1
GEOGRAPHICAL BREAKDOWNOF REPLIES FROM KIT USERS
Province or Territory
Number
British Columbia . . . . . . . . . . . . . . . Alberta . . . . . . . . . . . . . . . . . . . . . . . . Saskatchewan . . . . . . . . . . . . . . . . . . Manitoba . . . . . . . . . . . . . . . . . . . . . . Ontario . . . . . . . . . . . . . . . . . . . . . . . . Quebec . . . . . . . . . . . . . . . . . . . . . . . . New Brunswick . . . . . . . . . . . . . . . . . Nova Scotia . . . . . . . . . . . . . . . . . . . . Newfoundland . . . . . . . . . . . . . . . . . . Prince Edward Island . . . . . . . . . . . Northwest Territories . . . . . . . . . . . Yukon Territory . . . . . . . . . . . . . . . . Not designated . . . . . . . . . . . . . . . . . Total:
%
66 87 62 46 194 111 19 30 12 2 8 2 1
10.3 13.6 9.7 7.2 30.3 17.3 3.0 4.7 1.9 0.3 1.2 0.3 0.2
640
100.0
2 has been calculated as a p e r c e n t a g e of the total n u m b e r of l a b o r a t o r i e s u s i n g them, i.e., 640. The a v e r a g e n u m b e r of d i f f e r e n t k i n d s of kits used by the hospitals a n d o t h e r i n s t i t u t i o n s for the d e t e r m i n a t i o n of chemical a n d enzyme c o n s t i t u e n t s are also p r e s e n t e d in Table 2. K i t s designed to test for chemical c o n s t i t u e n t s were most f r e q u e n t l y used in hospitals of 51 to 600 bed capacity, w h e r e a s "~hose for enzymes were used more extensively in s o m e w h a t l a r g e r hospitals, i.e., of 201 to 700 capacity. A w e i g h t e d a v e r a g e was calculated to a d j u s t for the v a r y i n g n u m b e r of hospitals in each category a n d t h u s f i g u r e s of 5.4 a n d 4.2 per hospital were o b t a i n e d for the overall use of chemical and enzyme kits respectively. Table 3 shows the total volume of tests p e r f o r m e d m o n t h l y by kits in those l a b o r a t o r i e s which supplied this i n f o r m a t i o n on the r e t u r n e d q u e s t i o n n a i r e s . The data have a g a i n been categorized a c c o r d i n g to hospital size a n d a n a v e r a g e m o n t h l y volume of tests perf o r m e d by kits per l a b o r a t o r y has been calculated. The a v e r a g e m o n t h l y volume of tests p e r f o r m e d by kits would seem to parallel, to a c e r t a i n extent, t h e increased workload of hospitals of h i g h e r bed capacity. W i t h two possible exceptions, viz., 301-350 a n d 801900 bed hospitals, t h e r e is evidence of a h i g h e r volume of tests p e r f o r m e d by kits in hospitals over 200-bed
TABLE
2
DISTRIBUTION OF REPLIES TO QUESTIONNAIRE AND AVERAGENUMBER OF TYPES OF KITS RELATIVE TO HOSPITAL SIZE
Hospital Size 1 -50 beds . . . . . . . 5 1 - - 100 . . . . . . . . . . . 101 - - 150 . . . . . . . . . . . 1 5 1 - 200 . . . . . . . . . . . 2 0 1 - 250 . . . . . . . . . . . 2 5 1 - - 300 . . . . . . . . . . . 3 0 1 - 350 . . . . . . . . . . . 3 5 1 - 400 . . . . . . . . . . . 4 0 1 - 500 . . . . . . . . . . . 5 0 1 - 600 . . . . . . . . . . . 6 0 1 - 700 . . . . . . . . . . . 7 0 1 - 800 . . . . . . . . . . . 8 0 1 - 900 . . . . . . . . . . . 901 - - 1000 . . . . . . . . . . . > 1000 . . . . . . . . . . . Others** . . . . . . . . . . . . . . Total . . . . . . . . .
No. of Returns
No. Using Kits
Labs. Using Kits % of Total*
347 137 88 37 41 29 16 19 30 21 9 9 3 8 12 13
236 119 76 27 35 26 12 17 28 20 9 9 3 6 10 7
36.9 18.6 11.9 4.2 5.5 4.1 1.9 2.6 4.4 3.1 1.4 1.4 0.5 0.9 1.6 1.1
819
640
100.0
*Calculated as % of total number of laboratories using kits, i.e. 640 **Not included in the weighted average
Average No. Chemical Kits
Average No. Enzyme Kits
3.6 6.7 6.7 5.0 6.4 5.8 7.2 6.9 6.6 6.6 3.5 4.9 6.0 6.4 6.5 2.5 Weighted Average
5.4
1.9 4.9 5.5 3.7 6.3 5.5 5.3 8.1 7.0 6.2 6.6 4.7 4.0 3.9 7.4 3.5 Weighted Average
4.2
IN
VITRO
DIAGNOSTIC
KITS
IN
HOSPITAL
LABORATORIES
TABLE 3
TABLE
TOTAL VOLUME OF TESTS PERFORMED BY KITS IN RELATION TO HOSPITAL SIZE
H o s p i t a l Size 1 51 101 151 201 251 301 351 401 501 601 701 801 901
---
------------>
Average Number T e s t s per M o n t h per I n s t i t u t i o n
175 94 49 22 26 18 11 11 25 13 7 6 3 6 8
198 961 1302 934 2263 3077 1482 2878 2878 5058 2150 6343 1270 5172 4945
Total*...
474
*Only 474 or 7 4 . 1 % of t h e 640 l a b o r a t o r i e s f u r n i s h e d d a t a on the t o t a l m o n t h l y v o l u m e of t e s t s p e r f o r m e d b y l d t s
TABLE
4
COMPARATIVE USE OF KITS AS DEPICTED BY THREE SURVEYS A v e r a g e No. T y p e s of K i t s U s e d Per Hospital Year
No. H o s p i t a l s
1968 . . . . 1971 . . . . 1975 . . . .
Chemical
398 310 633
Enzyme
3.6 4.4 5.4
5
NUMBER OF LABORATORIES USING KITS FOR VARIOUS CLINICAL CHEMISTRY TESTS
No. Reporting
50 b e d s . . . . . . . . . 100 . . . . . . . . . . . . . 150 . . . . . . . . . . . . . 200 . . . . . . . . . . . . . 250 . . . . . . . . . . . . . . 300 . . . . . . . . . . . . . 350 . . . . . . . . . . . . . 400 . . . . . . . . . . . . . 500 . . . . . . . . . . . . . . 600 . . . . . . . . . . . . . . 700 . . . . . . . . . . . . . 800 . . . . . . . . . . . . . 900 . . . . . . . . . . . . . 1000 . . . . . . . . . . . . 1000 . . . . . . . . . . . . .
135
3.6 4.0 4.2
N a m e of T e s t
N o . of Labs.
% of L a b s .
54 21 106 229 227 46 138 192 3 87 40 98 3 301 81 126 24
8.4 3.3 16.6 35.8 35.5 7.2 21.6 30.0 0.5 13.6 6.3 15.3 0.5 47.0 12.7 19.7 3.8 2.8 1.7 0.8 5.3 1.3 23.3 5.9 0.8 14.1 14.1 7.7 11.1 3.,1 5.8 2.8 0.9
Ammonia .................. Barbiturate ................ Bicarbonate ................ Bilirubin ................... Calcium ................... Cephalin Cholesterol ........ Chloride ................... Cholesterol ................. Copper .................... Creatinine ................. E t h y l Alcohol . . . . . . . . . . . . . . Fibrinogen ................. F o r m i m i n o - L - G l u t a m i c Acid . Glucose .................... Hemoglobin ................ I r o n ( U I B C a n d / o r "FIBC) .. Lipids, T o t a l . . . . . . . . . . . . . . . Lipoproteins ........... t3-Lipoproteins . . . . . . . . . . Phospholipids .......... Magnesium ................ Phenylalanine .............. Phosphorus ................ Potassium .................. Protein-Bound Iodine ....... Proteins, Total . . . . . . . . . . . . . Albumin ............... Globulin ................. Salicylates ................. Serotonin . . . . . . . . . . . . . . . . . . Sodium .................... 17-Ketosteroids ............. 17-Ketogenic Steroids . . . . . . . Thymol Turbidity .......... Triglycerides ............... Urea Nitrogen . . . . . . . . . . . . . . Uric Acid . . . . . . . . . . . . . . . . . . V a n i l m a n d e l i c Acid . . . . . . . . . . Pregnancy Tests ............ Others .....................
18
11 5 34 8 149 38 5 90 90 19 71 '2'2 37 18 6 53 150 327 225 31 121 41
Total .....
51.1 35.2 4.8 18.9 6.4
3,375
TABLE 6 NUMBER OF LABORATORIES USING I'~.ITS FOR VARIOUS CLINICAL ENZYME TESTS N a m e of T e s t
No. of Labs.
Aldolase ................... Aminotransferase A l a n i n e (GPT} . . . . . . . . . Aminotransferase Aspartate (GOT) . . . . . . . Amylase ................... Cholinesterase .............. Creatine Phosphokinase (CPK) ................ C r e a t i n e P h o s p h o k i n a s e Isoenzymes ............... Glucose-6-Phosphate Dehydrogenase ......... ~-Hydroxybutyric Dehydrogenase ................. Isocitric Dehydrogenase ..... Lactic Dehydrogenase (LDH) L a c t i c D e h y d r o g e n a s e Isoenzymes ............... Leucine Arylamidase ........ Lipase ..................... P h o s p h a t a s e , Acid . . . . . . . . . . P h o s p h a t a s e , Acid ( P r o s t a t i c ) Phosphatase, Alkaline ....... P h o s p h a t a s e , A l k a l i n e Isoenzymes ............... Transpeptidase, z-Glutamyl., Others ..................... Total:
% of Labs.
30
4.7
214
33.4
TABLE 7
415 329 22
64.8 51.4 3.4
AVERAGE NUMBER OF TYPES OF R I A AND C P B KITS USED IN VARIOUS SIZE HOSPITALS
240
37.5
23
3.6
35
5.5
62 13 323
9.7 2.0 50.5
21 13 94 211 115 314
3.3 2.0 14.7 33.0 18.0 49.1
17 55 76
2.7 8.6 11.9
2,642
Average No. RIA Kits
H o s p i t a l Size 1 -50 b e d s 51100 . . . . . 101150 . . . . . 151200 . . . . . 201250 . . . . . 251300 . . . . . 301350 . . . . . 351400 . . . . . 401500 . . . . . 501600 . . . . . 601700 . . . . . 701800 . . . . . 801900 . . . . . 901 - - 1000 . . . . . > 10G0 . . . . .
Average No. CPB Kits
0.00 0.02 0.05 0.15 0.43 0.42 0.50 2.70 0.50 2.75 3.00 2.22 1.00 1.62 2.30 Weighted Average
0.38
0.00 0.13 0.28 0.48 1.11 1.19 1.20 1.41 0.93 1.10 0.75 1.55 2.00 0.25 1.50 Weighted Average
0.39
136
LOGAN AND
TAADA
TABLE 8 NUMBER
O F
TABLE 9
LABORATORIESUSING VARIOUS RIA
A N D
RIA No. of Labs.
Test
C P B KITS
NUMBER OF INDIVIDUAL BLOOD ANALYZER SYSTEMS IN USE IN HOSPITAL LABORATORIES
CPB
To of Labs.
No. of Labs.
To of Labs.
4 2 1
0.6 0.3 0.2
----
----
-8 3 --3 ---7 --1 -----
-1.3 0.5 --0.5 ---1.1 --0.2
ACTH ............ Aldosterone . . . . . . . . Calcitonin . . . . . . . . . Carcinoembryonic Antigen ( C E A ) . . . Cortisol . . . . . . . . . . . Cyclic A M P . . . . . . . . Cyclic G M P . . . . . . . Digitoxin . . . . . . . . . . Digoxin . . . . . . . . . . . . Estriol . . . . . . . . . . . . . Estradiol . . . . . . . . . . FSH . . . . . . . . . . . . . . Folic Acid . . . . . . . . . . Gastrin . . . . . . . . . . . . HCG .............. HCS (HPL) . . . . . . . . HGH .............. Hepatitis B Antigen IgE . . . . . . . . . . . . . . . Insulin . . . . . . . . . . . . LH ............... Progesterone . . . . . . . Prolactin . . . . . . . . . . Prostaglandins . . . . . . Renin Activity (Angiotensin I). TBG .............. TSH . . . . . . . . . . . . . . T-3 . . . . . . . . . . . . . . . T-4 . . . . . . . . . . . . . . . Testosterone . . . . . . . Vitamin B~2 . . . . . . . . Others . . . . . . . . . . . . .
4 6 3 1 1 39 3 2 16 6 7 1 7 10 16 3 16 9 1 1 1
0.6 0.9 0.5 0.2 0.2 6.1 0.5 0.5 2.5 0.9 1.1 0.2 1.1 1.6 2.5 0.5 2.5 1.4 0.2 0.2 0.2
--
--
----
----
17 -17 19 17 2 1 12
2.7 -2.7 3.0 2.7 0.3 0.2 1.9
-5 1 79 90 1 21 29
-0.8 0.2 12.3 14.1 0.2 3.3 4.5
Total . . . .
245
--
----
248
tests for aspartate aminotransferase (GOT) were performed by kit in more laboratories than were tests for urea nitrogen (see Table 5), the test most frequently performed by kit in the chemical group. Among other enzyme tests, kits were most frequently used for amylase, LDH, alkaline phosphatase, CPK, alanine aminotransferase (GPT) and acid phosphatase. When these data are examined in relation to h o s p i t a l size, a s d e s c r i b e d f o r t h e c h e m i c a l g r o u p , s e v e r a l i n t e r e s t i n g f a c t s e m e r g e . I t is e v i d e n t t h a t t h e r e is a m u c h h i g h e r p e r c e n t a g e u s a g e o f k i t s f o r enzyme tests than for chemical tests among the tests already named as being most frequently performed by kit. For example, the average percentage use of kits among the hospital-bed categories from 1-50 through to 601-700 for aspartate aminotransferase is 81.3% compared to 48.0% for urea nitrogen. Among t h e e n z y m e k i t s , a l t h o u g h t h e r e is a f a i r l y s i g n i f i c a n t u s e o f k i t s e v e n a m o n g h o s p i t a l s o f less t h a n 50 b e d s , the most frequent use begins in hospitals of 51-100 bed capacity. Exceptions to this among the most frequently performed tests listed above are CPK and GPT which begin to show increased use in hospitals o f 2 0 1 - 2 5 0 a n d 1 0 1 - 1 5 0 b e d size, r e s p e c t i v e l y . T h i s increased use of kits for enzyme tests persists at l e a s t u p to h o s p i t a l s o f 6 0 0 a n d 7 0 0 - b e d c a p a c i t y a n d in the case of GOT, LDH and CPK seems to continue right through to the very largest hospitals. Table 7 shows the data obtained for the use of kits in performing RIA and CPB tests in relation to h o s p i t a l size. A n o v e r a l l w e i g h t e d a v e r a g e h a s b e e n
1971 Name of System Eskalab . . . . . . . . . . . . Diagnostest . . . . . . . . Ames/BMI ........ Bio-Dynamics . . . . . . Clinicard . . . . . . . . . . . D u p o n t ACA . . . . . . .
1975
No.
To
No.
To
24 7 2 4 ---
7.2 2.1 0.6 1.2 ---
69 49 23 10 7 2
10.8 7.7 3.6 1.6 1.1 0.3
calculated as was done for the chemical and enzyme g r o u p s a n d i t will b e n o t e d t h a t t h e u s e o f k i t s is very similar for the two techniques. We regard these data as minimum-usage figures as we are not certain whether the questionnaires reached the correct laboratories in the larger hospitals where the tests are often c a r r i e d o u t in n u c l e a r m e d i c i n e d e p a r t m e n t s . For R I A k i t s , t h e m o r e e x t e n s i v e u s e is i n l a r g e h o s p i t a l s o f 3 5 1 - b e d c a p a c i t y a n d up, w h e r e a s t h e u s e o f C P B k i t s i n c r e a s e s in h o s p i t a l s o f m o r e t h a n 200 b e d s . The number of laboratories using kits for individual R I A a n d C P B t e s t s a r e s h o w n i n T a b l e 8. T h e t e s t s most frequently performed by a RIA kit (in descendi n g o r d e r o f f r e q u e n c y ) a r e : d i g o x i n , T-3, T-4, T S H , renin, FSH, hepatitis B antigen and insulin. The more frequent use of kits for digoxin, T-3 and T-4 t e s t i n g w a s f o u n d t o o c c u r i n h o s p i t a l s f r o m 251 b e d s u p a n d f o r t h e o t h e r f i v e t e s t s in h o s p i t a l s o f m o r e t h a n 351 b e d s . I n all c a s e s t h e u s e o f R I A k i t s w a s e v i d e n t i n all o f t h e l a r g e h o s p i t a l c a t e g o r i e s . The kits most frequently used for CPB tests (in d e s c e n d i n g o r d e r l w e r e : T-4, T - 3 a n d V i t a m i n B,.... More extensive use of kits for these tests occurred in hospitals of greater than 200 beds. In the case of T-3 and T-4 a significant number of kits were used in h o s p i t a l s f r o m 51 t o 200 b e d s , b u t n o k i t s w e r e reported to be used in these hospitals for Vitamin B, t e s t s . I n all t h r e e c a s e s i n c r e a s e d u s e o f k i t s c o n tinued through the large hospitals. I n T a b l e 9, t h e e x t e n t o f u s e o f b l o o d a n a l y z e r s y s t e m s i n h o s p i t a l l a b o r a t o r i e s is c o m p a r e d w i t h t h a t r e p o r t e d i n t h e 1971 s u r v e y . A s i n 1971, t h e E s k a l a b S y s t e m w a s t h e m o s t p o p u l a r t y p e . T h e 1975 s u r v e y shows that the use of Eskalab, Diagnostest and Ames/ BMI analyzers has increased significantly, whereas t h e r e w a s a r e l a t i v e l y s m a l l i n c r e a s e in u s e o f t h e Bio-Dynamics System. Seven laboratories now report using the IL/Harleco Clinicard System and two, the Dupont ACA Analyzer. T h e r e w e r e 614 replies which indicated how kits w e r e used. a n d , o f t h e s e , 4 1 4 r e p o r t e d u s i n g a t l e a s t one kit on a routine basis. Nineteen indicated using k i t s o n a s t a n d b y b a s i s o n l y a n d 181 r e p o r t e d u s i n g them for routine testing as well as for standby. As was reported in t h e 1 9 6 8 s u r v e y '2), a s i g n i f i c a n t number of hospitals of under 50-bed capacity used kits for standby purposes. An examination of the names of the manufacturers of kits for chemical and enzyme tests reveals that eight companies supplied more than half of the laboratories. For RIA and CPB tests, five manufacturers provided a similar coverage.
IN VITRO DIAGNOSTIC KITS IN HOSPITAL LABORATORIES DISCUSSION
The results of the latest survey indicate t h a t both the use of in vitro diagnostic kits, and of complete analyzer systems where the r e a g e n t s are specifically designed for the system has continued to increase. W i t h the p o p u l a r t r e n d t o w a r d r a d i o i m m u n o a s s a y s and competitive binding type radioassays, it is evident t h a t we are now seeing a s i g n i f i c a n t development in kits for these techniques. In vitro diagnostic kits and associated blood analyzer systems have recently come under the r e g u l a t o r y control of both the Canadian and United States governments, as medical devices. However, we are f a r from realizing the ideal s i t u a t i o n where all the products on the m a r k e t p e r f o r m e i t h e r in accordance with the m a n u f a c t u r e r ' s claims, or are capable of supplying the clinician with the reliable data needed. Therefore, the l a b o r a t o r y a n a l y s t must continue to choose carefully from among the available commercial products. Since the advent of r e g u l a t o r y control of medical devices in Canada, there has been a s h i f t of emphasis in our own l a b o r a t o r y away from the d i r e c t evaluation of kits and associated i n s t r u ments t o w a r d the development of reference methods. The l a t t e r can then be used to assign t a r g e t values to serum pools which are then d i s t r i b u t e d to clinical l a b o r a t o r i e s across Canada for the v o l u n t a r y monitoring not only of the p e r f o r m a n c e of in vitro diagnostic products but all routine methods in use. This is a
137
p a r t i c u l a r l y useful means of checking the accuracy of procedures and, when results of such surveys show t h a t a considerable bias is associated with a method or a kit procedure in a n u m b e r of laboratories, the l a b o r a t o r y d i r e c t o r may well consider changing to a more accurate method. Studies involving the application of reference methods are under way and a r e p o r t of our f i n d i n g s for calcium, magnesium and c r e a t i n i n e procedures has already been presented'SL ACKNOWLEDGEMENT
The authors would like to t h a n k all the l a b o r a t o r y directors and t h e i r s t a f f who by t h e i r response to the questionnaire made this study possible. They are also indebted to Maurice Loshuk for his valuable assistance in the p r e p a r a t i o n , mailing and processing of the questionnaires. REFF-,RENCES
1. Logan, J. E. (1972). Crit. Rev. Clin. Lab. Sci., 3: 271289. 2. Logan, J. E., Renton, H. M., and Allen, R. H. (1970). Cli~. Biochem., 3: 81-89. 3. Weatherburn, M. W., and Logan, J. E. (1976). Clin. Biochem., 9: P6, #3.
The Use of In Vitro Diagnostic Kits in Hospital Laboratories in Canada J . E . L O G A N a n d D. R. T A A D A
Bureau of Clinical Chemistry and Hematology, Laboratory Centre for Disease Control, Health Protection Branch, Health and Welfare C a n a d a , O t t a w a , Ontario (Accepted
February
CLBIA, 1'0, (3) 133-137 (1977) Clin. Bioche~. Logan, J. E., and Taada, D. R.
Bureau of Clinical Chemistry and Hematology, Laboratory Centre for Disease Control, Health Protection Branch, Health and Welfare, Ottawa, Ontario K I A OL2 T H E USE OF IN VITRO DIAGNOSTIC KITS IN H O S P I T A L LABORATORIES IN CANADA 1. A survey conducted among hospital laboratories has yielded data from 640 institutions concerning the use of diagnostic kits and reagents in Canada. 2. Kits designed to test for chemical constituents were most frequently used in hospitals of 51 to 600 bed capacity whereas the ones for enzymes were most extensively used in 201 to 700 bed-size institutions. Kits based on the CPB principles were generally used in hospitals of more than 200 beds whereas those based on RIA were only in frequent use where the bed capacity was 351 or more. 3. The following tests were most often performed by kits': aminotransferases, amylase, urea, LDH, phosphatases, glucose, CPK, bilirubin, calcium, uric acid, T-4, T-3, digoxin and vitamin B12. 4. The survey reflects a continuing and increasing usage of in vitro diagnostic kits and associated blood analyzer systems. It also indicates a significant adoption of assay kits which utilize RIA and CPB principles.
7, 1 9 7 7 )
s u r a n c e p r o g r a m is provided. Two s u r v e y s on t h e e x t e n t of use of kits and a n a l y z e r s y s t e m s have been c a r r i e d out a n d r e p o r t e d ' ' ' ~ . The r e s u l t s of a t h i r d such s u r v e y conducted in September, 1975, are p r e s e n t e d here as u p d a t i n g i n f o r m a t i o n * .
MI~I~IOD A questionnaire was prepared and mailed to all 1387 hospitals in Canada. Hospitals were surveyed regardless of whether or not they possessed clinical laboratory facilities, and they were requested to reply even though no kits or associated analyzer systems were used. Hospital personnel were requested to indicate the bed capacity of their institutions and to t r y to estimate the total volume of tests per month performed by kits. Three check-off lists of tests were provided, for determination of 39 chemical constituents, 20 enzyme constituents, and 36 for constituents tested either by radioimmunoassay (RIA) or competitive protein-binding (CPB) techniques. This was the first time that the latter categories were included in a survey. In addition to checking whether a kit was used for the test, the name of the kit and its m a n u f a c t u r e r were requested and an indication of whether it was used on a routine or standby basis. For chemical and enzyme constituents the participants were asked to name the analyzer system used when the kit formed an integral part of such a system, e.g., Eskalab, Clinicard, Dupont ACA, etc. In the cases of RIA and CPB tests, the type of isotope used was requested. Systemsort punch cards were employed to record the information received from the completed questionnaires. RESULTS
THE IMPROVEMENT of the q u a l i t y of p e r f o r m a n c e of l a b o r a t o r y t e s t i n g in clinical c h e m i s t r y in C a n a d a has been a concern of the L a b o r a t o r y C e n t r e for Disease Control since 1952. M a n y e v a l u a t i o n s of in vitro d i a g n o s t i c kits a n d r e a g e n t sets available on the C a n a d i a n m a r k e t have been c a r r i e d out a n d r e f e r ences to most of the p u b l i s h e d r e p o r t s are c o n t a i n e d in the b i b l i o g r a p h y of a p r e v i o u s r e v i e w a r t i c l e " ' . More recently, the l a b o r a t o r y has been active i n t h e development a n d e s t a b l i s h m e n t of r e f e r e n c e m e t h o d s a n d m a t e r i a l s w h e r e b y the p e r f o r m a n c e of m e t h o d s in r o u t i n e use m a y be m o n i t o r e d . T h i s includes e v a l u a t i n g the p e r f o r m a n c e s of clinical c h e m i s t r y kits a n d associated blood c h e m i s t r y a n a l y z e r systems. Thus, i n f o r m a t i o n c o m p l e m e n t a r y to a g e n e r a l q u a l i t y as-
Replies to the s i n g l e m a i l i n g of the q u e s t i o n n a i r e were received f r o m 819 hospital l a b o r a t o r i e s . T h i s was c o n s i d e r e d to be quite a good response since it r e p r e s e n t e d a b o u t 59% of the total n u m b e r dist r i b u t e d . Of the 819 replies, 640 r e p o r t e d u s i n g one or more kits in t h e i r l a b o r a t o r i e s . A geographica] b r e a k d o w n of the replies of k i t u s e r s is shown i n Table 1. Table 2 shows t h e d i s t r i b u t i o n of all r e t u r n s to the q u e s t i o n n a i r e a n d the n u m b e r u s i n g kits categorized according to hospital size. F o r hospitals of 150bed c a p a c i t y or less, 431 r e p o r t e d u s i n g k i t s ; t h i s is 67.3% of the total, a h i g h e r p e r c e n t a g e t h a n t h a t f o u n d in 1968 '2). T h e p e r c e n t a g e of total l a b o r a t o r i e s u s i n g kits a c c o r d i n g to hospital sizes shown in T a b l e
Correspondence: Dr. J. E. Logan, Bureau of Clinical Chemistry & Hematology, Laboratory Centre for Disease Control, Tunney's Pasture, Ottawa, Ontario, K1A 0L2
*Presented in p a r t at the 20th A n n u a l CSCC Conference, Ottawa, July 13-16, 1976 - - see CIin. Bioche~n. 9: P6, #3 (1976).
134
LOGAN AND TAADA TABLE
capacity. I t is n o t k n o w n w h y the volume reported is less in the two categories m e n t i o n e d above. T h e n u m b e r of hospitals r e p o r t i n g in the l a t t e r case is only t h r e e and as such does n o t c o n s t i t u t e a good s t a t i s t i c a l sample. I n T a b l e 4, c o m p a r i s o n of the w e i g h t e d a v e r a g e s f r o m Table 2 is made w i t h those calculated f r o m data o b t a i n e d in our 1968 a n d 1971 s u r v e y s ' ' , ' ~ ' These data show a c o n t i n u i n g i n c r e a s e d use of kits with the a v e r a g e n u m b e r per hospital used for chemical c o n s t i t u e n t s exceeding t h a t for enzymes. The fact t h a t kits are available f o r a g r e a t e r v a r i e t y of chemical tests t h a n f o r enzyme tests coupled w i t h the knowledge t h a t the total l a b o r a t o r y workload for chemical tests would, in most laboratories, be cons i d e r a b l y g r e a t e r t h a n t h a t for enzyme tests c e r t a i n l y c o n t r i b u t e s to these s t a t i s t i c s . One could conclude f r o m these f a c t o r s t h a t use of kits for enzyme t e s t i n g m u s t c o n s t i t u t e a g r e a t e r p e r c e n t a g e of the total workload for enzyme a n a l y s e s t h a n in the corresponding s i t u a t i o n for chemical c o n s t i t u e n t s . Table 5 shows the n u m b e r of l a b o r a t o r i e s u s i n g kits for each of the chemical tests expressed as a perc e n t a g e of the total 640 l a b o r a t o r i e s u s i n g kits. K i t s were most f r e q u e n t l y used for t h e following tests (in d e s c e n d i n g o r d e r ) : urea n i t r o g e n , glucose, bilir u b i n , calcium, uric acid, cholesterol, t r i g l y c e r i d e s a n d phosphorus. A n e x a m i n a t i o n of the r a t i o of the n u m b e r of hospitals u s i n g a k i t for a p a r t i c u l a r c o n s t i t u e n t i n r e l a t i o n to the total n u m b e r of hospitals in t h a t size c a t e g o r y revealed s i g n i f i c a n t p a t t e r n s . The most f r e q u e n t use of kits for urea n i t r o g e n , glucose a n d b i l i r u b i n was f o u n d to be in the f i r s t t h r e e categories, i.e., small hospitals up to 150-bed capacity. F o r cholesterol, uric acid, calcium a n d phosphorus, more ext e n s i v e k i t use showed up in the 51-100 bed c a t e g o r y and decreased a g a i n a f t e r 350, 500, 600 a n d 700-bed capacities, respectively. F o r t r i g l y c e r i d e s , a s i g n i f i c a n t use of kits is n o t f o u n d u n t i l a 201-250 bed c a p a c i t y is reached a n d is t h e n c o n t i n u o u s up to 700 beds. Data are shown in Table 6 for the e x t e n t of use kits for enzyme d e t e r m i n a t i o n s . I t will be n o t e d t h a t
1
GEOGRAPHICAL BREAKDOWNOF REPLIES FROM KIT USERS
Province or Territory
Number
British Columbia . . . . . . . . . . . . . . . Alberta . . . . . . . . . . . . . . . . . . . . . . . . Saskatchewan . . . . . . . . . . . . . . . . . . Manitoba . . . . . . . . . . . . . . . . . . . . . . Ontario . . . . . . . . . . . . . . . . . . . . . . . . Quebec . . . . . . . . . . . . . . . . . . . . . . . . New Brunswick . . . . . . . . . . . . . . . . . Nova Scotia . . . . . . . . . . . . . . . . . . . . Newfoundland . . . . . . . . . . . . . . . . . . Prince Edward Island . . . . . . . . . . . Northwest Territories . . . . . . . . . . . Yukon Territory . . . . . . . . . . . . . . . . Not designated . . . . . . . . . . . . . . . . . Total:
%
66 87 62 46 194 111 19 30 12 2 8 2 1
10.3 13.6 9.7 7.2 30.3 17.3 3.0 4.7 1.9 0.3 1.2 0.3 0.2
640
100.0
2 has been calculated as a p e r c e n t a g e of the total n u m b e r of l a b o r a t o r i e s u s i n g them, i.e., 640. The a v e r a g e n u m b e r of d i f f e r e n t k i n d s of kits used by the hospitals a n d o t h e r i n s t i t u t i o n s for the d e t e r m i n a t i o n of chemical a n d enzyme c o n s t i t u e n t s are also p r e s e n t e d in Table 2. K i t s designed to test for chemical c o n s t i t u e n t s were most f r e q u e n t l y used in hospitals of 51 to 600 bed capacity, w h e r e a s "~hose for enzymes were used more extensively in s o m e w h a t l a r g e r hospitals, i.e., of 201 to 700 capacity. A w e i g h t e d a v e r a g e was calculated to a d j u s t for the v a r y i n g n u m b e r of hospitals in each category a n d t h u s f i g u r e s of 5.4 a n d 4.2 per hospital were o b t a i n e d for the overall use of chemical and enzyme kits respectively. Table 3 shows the total volume of tests p e r f o r m e d m o n t h l y by kits in those l a b o r a t o r i e s which supplied this i n f o r m a t i o n on the r e t u r n e d q u e s t i o n n a i r e s . The data have a g a i n been categorized a c c o r d i n g to hospital size a n d a n a v e r a g e m o n t h l y volume of tests perf o r m e d by kits per l a b o r a t o r y has been calculated. The a v e r a g e m o n t h l y volume of tests p e r f o r m e d by kits would seem to parallel, to a c e r t a i n extent, t h e increased workload of hospitals of h i g h e r bed capacity. W i t h two possible exceptions, viz., 301-350 a n d 801900 bed hospitals, t h e r e is evidence of a h i g h e r volume of tests p e r f o r m e d by kits in hospitals over 200-bed
TABLE
2
DISTRIBUTION OF REPLIES TO QUESTIONNAIRE AND AVERAGENUMBER OF TYPES OF KITS RELATIVE TO HOSPITAL SIZE
Hospital Size 1 -50 beds . . . . . . . 5 1 - - 100 . . . . . . . . . . . 101 - - 150 . . . . . . . . . . . 1 5 1 - 200 . . . . . . . . . . . 2 0 1 - 250 . . . . . . . . . . . 2 5 1 - - 300 . . . . . . . . . . . 3 0 1 - 350 . . . . . . . . . . . 3 5 1 - 400 . . . . . . . . . . . 4 0 1 - 500 . . . . . . . . . . . 5 0 1 - 600 . . . . . . . . . . . 6 0 1 - 700 . . . . . . . . . . . 7 0 1 - 800 . . . . . . . . . . . 8 0 1 - 900 . . . . . . . . . . . 901 - - 1000 . . . . . . . . . . . > 1000 . . . . . . . . . . . Others** . . . . . . . . . . . . . . Total . . . . . . . . .
No. of Returns
No. Using Kits
Labs. Using Kits % of Total*
347 137 88 37 41 29 16 19 30 21 9 9 3 8 12 13
236 119 76 27 35 26 12 17 28 20 9 9 3 6 10 7
36.9 18.6 11.9 4.2 5.5 4.1 1.9 2.6 4.4 3.1 1.4 1.4 0.5 0.9 1.6 1.1
819
640
100.0
*Calculated as % of total number of laboratories using kits, i.e. 640 **Not included in the weighted average
Average No. Chemical Kits
Average No. Enzyme Kits
3.6 6.7 6.7 5.0 6.4 5.8 7.2 6.9 6.6 6.6 3.5 4.9 6.0 6.4 6.5 2.5 Weighted Average
5.4
1.9 4.9 5.5 3.7 6.3 5.5 5.3 8.1 7.0 6.2 6.6 4.7 4.0 3.9 7.4 3.5 Weighted Average
4.2
IN
VITRO
DIAGNOSTIC
KITS
IN
HOSPITAL
LABORATORIES
TABLE 3
TABLE
TOTAL VOLUME OF TESTS PERFORMED BY KITS IN RELATION TO HOSPITAL SIZE
H o s p i t a l Size 1 51 101 151 201 251 301 351 401 501 601 701 801 901
---
------------>
Average Number T e s t s per M o n t h per I n s t i t u t i o n
175 94 49 22 26 18 11 11 25 13 7 6 3 6 8
198 961 1302 934 2263 3077 1482 2878 2878 5058 2150 6343 1270 5172 4945
Total*...
474
*Only 474 or 7 4 . 1 % of t h e 640 l a b o r a t o r i e s f u r n i s h e d d a t a on the t o t a l m o n t h l y v o l u m e of t e s t s p e r f o r m e d b y l d t s
TABLE
4
COMPARATIVE USE OF KITS AS DEPICTED BY THREE SURVEYS A v e r a g e No. T y p e s of K i t s U s e d Per Hospital Year
No. H o s p i t a l s
1968 . . . . 1971 . . . . 1975 . . . .
Chemical
398 310 633
Enzyme
3.6 4.4 5.4
5
NUMBER OF LABORATORIES USING KITS FOR VARIOUS CLINICAL CHEMISTRY TESTS
No. Reporting
50 b e d s . . . . . . . . . 100 . . . . . . . . . . . . . 150 . . . . . . . . . . . . . 200 . . . . . . . . . . . . . 250 . . . . . . . . . . . . . . 300 . . . . . . . . . . . . . 350 . . . . . . . . . . . . . 400 . . . . . . . . . . . . . 500 . . . . . . . . . . . . . . 600 . . . . . . . . . . . . . . 700 . . . . . . . . . . . . . 800 . . . . . . . . . . . . . 900 . . . . . . . . . . . . . 1000 . . . . . . . . . . . . 1000 . . . . . . . . . . . . .
135
3.6 4.0 4.2
N a m e of T e s t
N o . of Labs.
% of L a b s .
54 21 106 229 227 46 138 192 3 87 40 98 3 301 81 126 24
8.4 3.3 16.6 35.8 35.5 7.2 21.6 30.0 0.5 13.6 6.3 15.3 0.5 47.0 12.7 19.7 3.8 2.8 1.7 0.8 5.3 1.3 23.3 5.9 0.8 14.1 14.1 7.7 11.1 3.,1 5.8 2.8 0.9
Ammonia .................. Barbiturate ................ Bicarbonate ................ Bilirubin ................... Calcium ................... Cephalin Cholesterol ........ Chloride ................... Cholesterol ................. Copper .................... Creatinine ................. E t h y l Alcohol . . . . . . . . . . . . . . Fibrinogen ................. F o r m i m i n o - L - G l u t a m i c Acid . Glucose .................... Hemoglobin ................ I r o n ( U I B C a n d / o r "FIBC) .. Lipids, T o t a l . . . . . . . . . . . . . . . Lipoproteins ........... t3-Lipoproteins . . . . . . . . . . Phospholipids .......... Magnesium ................ Phenylalanine .............. Phosphorus ................ Potassium .................. Protein-Bound Iodine ....... Proteins, Total . . . . . . . . . . . . . Albumin ............... Globulin ................. Salicylates ................. Serotonin . . . . . . . . . . . . . . . . . . Sodium .................... 17-Ketosteroids ............. 17-Ketogenic Steroids . . . . . . . Thymol Turbidity .......... Triglycerides ............... Urea Nitrogen . . . . . . . . . . . . . . Uric Acid . . . . . . . . . . . . . . . . . . V a n i l m a n d e l i c Acid . . . . . . . . . . Pregnancy Tests ............ Others .....................
18
11 5 34 8 149 38 5 90 90 19 71 '2'2 37 18 6 53 150 327 225 31 121 41
Total .....
51.1 35.2 4.8 18.9 6.4
3,375
TABLE 6 NUMBER OF LABORATORIES USING I'~.ITS FOR VARIOUS CLINICAL ENZYME TESTS N a m e of T e s t
No. of Labs.
Aldolase ................... Aminotransferase A l a n i n e (GPT} . . . . . . . . . Aminotransferase Aspartate (GOT) . . . . . . . Amylase ................... Cholinesterase .............. Creatine Phosphokinase (CPK) ................ C r e a t i n e P h o s p h o k i n a s e Isoenzymes ............... Glucose-6-Phosphate Dehydrogenase ......... ~-Hydroxybutyric Dehydrogenase ................. Isocitric Dehydrogenase ..... Lactic Dehydrogenase (LDH) L a c t i c D e h y d r o g e n a s e Isoenzymes ............... Leucine Arylamidase ........ Lipase ..................... P h o s p h a t a s e , Acid . . . . . . . . . . P h o s p h a t a s e , Acid ( P r o s t a t i c ) Phosphatase, Alkaline ....... P h o s p h a t a s e , A l k a l i n e Isoenzymes ............... Transpeptidase, z-Glutamyl., Others ..................... Total:
% of Labs.
30
4.7
214
33.4
TABLE 7
415 329 22
64.8 51.4 3.4
AVERAGE NUMBER OF TYPES OF R I A AND C P B KITS USED IN VARIOUS SIZE HOSPITALS
240
37.5
23
3.6
35
5.5
62 13 323
9.7 2.0 50.5
21 13 94 211 115 314
3.3 2.0 14.7 33.0 18.0 49.1
17 55 76
2.7 8.6 11.9
2,642
Average No. RIA Kits
H o s p i t a l Size 1 -50 b e d s 51100 . . . . . 101150 . . . . . 151200 . . . . . 201250 . . . . . 251300 . . . . . 301350 . . . . . 351400 . . . . . 401500 . . . . . 501600 . . . . . 601700 . . . . . 701800 . . . . . 801900 . . . . . 901 - - 1000 . . . . . > 10G0 . . . . .
Average No. CPB Kits
0.00 0.02 0.05 0.15 0.43 0.42 0.50 2.70 0.50 2.75 3.00 2.22 1.00 1.62 2.30 Weighted Average
0.38
0.00 0.13 0.28 0.48 1.11 1.19 1.20 1.41 0.93 1.10 0.75 1.55 2.00 0.25 1.50 Weighted Average
0.39
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LOGAN AND
TAADA
TABLE 8 NUMBER
O F
TABLE 9
LABORATORIESUSING VARIOUS RIA
A N D
RIA No. of Labs.
Test
C P B KITS
NUMBER OF INDIVIDUAL BLOOD ANALYZER SYSTEMS IN USE IN HOSPITAL LABORATORIES
CPB
To of Labs.
No. of Labs.
To of Labs.
4 2 1
0.6 0.3 0.2
----
----
-8 3 --3 ---7 --1 -----
-1.3 0.5 --0.5 ---1.1 --0.2
ACTH ............ Aldosterone . . . . . . . . Calcitonin . . . . . . . . . Carcinoembryonic Antigen ( C E A ) . . . Cortisol . . . . . . . . . . . Cyclic A M P . . . . . . . . Cyclic G M P . . . . . . . Digitoxin . . . . . . . . . . Digoxin . . . . . . . . . . . . Estriol . . . . . . . . . . . . . Estradiol . . . . . . . . . . FSH . . . . . . . . . . . . . . Folic Acid . . . . . . . . . . Gastrin . . . . . . . . . . . . HCG .............. HCS (HPL) . . . . . . . . HGH .............. Hepatitis B Antigen IgE . . . . . . . . . . . . . . . Insulin . . . . . . . . . . . . LH ............... Progesterone . . . . . . . Prolactin . . . . . . . . . . Prostaglandins . . . . . . Renin Activity (Angiotensin I). TBG .............. TSH . . . . . . . . . . . . . . T-3 . . . . . . . . . . . . . . . T-4 . . . . . . . . . . . . . . . Testosterone . . . . . . . Vitamin B~2 . . . . . . . . Others . . . . . . . . . . . . .
4 6 3 1 1 39 3 2 16 6 7 1 7 10 16 3 16 9 1 1 1
0.6 0.9 0.5 0.2 0.2 6.1 0.5 0.5 2.5 0.9 1.1 0.2 1.1 1.6 2.5 0.5 2.5 1.4 0.2 0.2 0.2
--
--
----
----
17 -17 19 17 2 1 12
2.7 -2.7 3.0 2.7 0.3 0.2 1.9
-5 1 79 90 1 21 29
-0.8 0.2 12.3 14.1 0.2 3.3 4.5
Total . . . .
245
--
----
248
tests for aspartate aminotransferase (GOT) were performed by kit in more laboratories than were tests for urea nitrogen (see Table 5), the test most frequently performed by kit in the chemical group. Among other enzyme tests, kits were most frequently used for amylase, LDH, alkaline phosphatase, CPK, alanine aminotransferase (GPT) and acid phosphatase. When these data are examined in relation to h o s p i t a l size, a s d e s c r i b e d f o r t h e c h e m i c a l g r o u p , s e v e r a l i n t e r e s t i n g f a c t s e m e r g e . I t is e v i d e n t t h a t t h e r e is a m u c h h i g h e r p e r c e n t a g e u s a g e o f k i t s f o r enzyme tests than for chemical tests among the tests already named as being most frequently performed by kit. For example, the average percentage use of kits among the hospital-bed categories from 1-50 through to 601-700 for aspartate aminotransferase is 81.3% compared to 48.0% for urea nitrogen. Among t h e e n z y m e k i t s , a l t h o u g h t h e r e is a f a i r l y s i g n i f i c a n t u s e o f k i t s e v e n a m o n g h o s p i t a l s o f less t h a n 50 b e d s , the most frequent use begins in hospitals of 51-100 bed capacity. Exceptions to this among the most frequently performed tests listed above are CPK and GPT which begin to show increased use in hospitals o f 2 0 1 - 2 5 0 a n d 1 0 1 - 1 5 0 b e d size, r e s p e c t i v e l y . T h i s increased use of kits for enzyme tests persists at l e a s t u p to h o s p i t a l s o f 6 0 0 a n d 7 0 0 - b e d c a p a c i t y a n d in the case of GOT, LDH and CPK seems to continue right through to the very largest hospitals. Table 7 shows the data obtained for the use of kits in performing RIA and CPB tests in relation to h o s p i t a l size. A n o v e r a l l w e i g h t e d a v e r a g e h a s b e e n
1971 Name of System Eskalab . . . . . . . . . . . . Diagnostest . . . . . . . . Ames/BMI ........ Bio-Dynamics . . . . . . Clinicard . . . . . . . . . . . D u p o n t ACA . . . . . . .
1975
No.
To
No.
To
24 7 2 4 ---
7.2 2.1 0.6 1.2 ---
69 49 23 10 7 2
10.8 7.7 3.6 1.6 1.1 0.3
calculated as was done for the chemical and enzyme g r o u p s a n d i t will b e n o t e d t h a t t h e u s e o f k i t s is very similar for the two techniques. We regard these data as minimum-usage figures as we are not certain whether the questionnaires reached the correct laboratories in the larger hospitals where the tests are often c a r r i e d o u t in n u c l e a r m e d i c i n e d e p a r t m e n t s . For R I A k i t s , t h e m o r e e x t e n s i v e u s e is i n l a r g e h o s p i t a l s o f 3 5 1 - b e d c a p a c i t y a n d up, w h e r e a s t h e u s e o f C P B k i t s i n c r e a s e s in h o s p i t a l s o f m o r e t h a n 200 b e d s . The number of laboratories using kits for individual R I A a n d C P B t e s t s a r e s h o w n i n T a b l e 8. T h e t e s t s most frequently performed by a RIA kit (in descendi n g o r d e r o f f r e q u e n c y ) a r e : d i g o x i n , T-3, T-4, T S H , renin, FSH, hepatitis B antigen and insulin. The more frequent use of kits for digoxin, T-3 and T-4 t e s t i n g w a s f o u n d t o o c c u r i n h o s p i t a l s f r o m 251 b e d s u p a n d f o r t h e o t h e r f i v e t e s t s in h o s p i t a l s o f m o r e t h a n 351 b e d s . I n all c a s e s t h e u s e o f R I A k i t s w a s e v i d e n t i n all o f t h e l a r g e h o s p i t a l c a t e g o r i e s . The kits most frequently used for CPB tests (in d e s c e n d i n g o r d e r l w e r e : T-4, T - 3 a n d V i t a m i n B,.... More extensive use of kits for these tests occurred in hospitals of greater than 200 beds. In the case of T-3 and T-4 a significant number of kits were used in h o s p i t a l s f r o m 51 t o 200 b e d s , b u t n o k i t s w e r e reported to be used in these hospitals for Vitamin B, t e s t s . I n all t h r e e c a s e s i n c r e a s e d u s e o f k i t s c o n tinued through the large hospitals. I n T a b l e 9, t h e e x t e n t o f u s e o f b l o o d a n a l y z e r s y s t e m s i n h o s p i t a l l a b o r a t o r i e s is c o m p a r e d w i t h t h a t r e p o r t e d i n t h e 1971 s u r v e y . A s i n 1971, t h e E s k a l a b S y s t e m w a s t h e m o s t p o p u l a r t y p e . T h e 1975 s u r v e y shows that the use of Eskalab, Diagnostest and Ames/ BMI analyzers has increased significantly, whereas t h e r e w a s a r e l a t i v e l y s m a l l i n c r e a s e in u s e o f t h e Bio-Dynamics System. Seven laboratories now report using the IL/Harleco Clinicard System and two, the Dupont ACA Analyzer. T h e r e w e r e 614 replies which indicated how kits w e r e used. a n d , o f t h e s e , 4 1 4 r e p o r t e d u s i n g a t l e a s t one kit on a routine basis. Nineteen indicated using k i t s o n a s t a n d b y b a s i s o n l y a n d 181 r e p o r t e d u s i n g them for routine testing as well as for standby. As was reported in t h e 1 9 6 8 s u r v e y '2), a s i g n i f i c a n t number of hospitals of under 50-bed capacity used kits for standby purposes. An examination of the names of the manufacturers of kits for chemical and enzyme tests reveals that eight companies supplied more than half of the laboratories. For RIA and CPB tests, five manufacturers provided a similar coverage.
IN VITRO DIAGNOSTIC KITS IN HOSPITAL LABORATORIES DISCUSSION
The results of the latest survey indicate t h a t both the use of in vitro diagnostic kits, and of complete analyzer systems where the r e a g e n t s are specifically designed for the system has continued to increase. W i t h the p o p u l a r t r e n d t o w a r d r a d i o i m m u n o a s s a y s and competitive binding type radioassays, it is evident t h a t we are now seeing a s i g n i f i c a n t development in kits for these techniques. In vitro diagnostic kits and associated blood analyzer systems have recently come under the r e g u l a t o r y control of both the Canadian and United States governments, as medical devices. However, we are f a r from realizing the ideal s i t u a t i o n where all the products on the m a r k e t p e r f o r m e i t h e r in accordance with the m a n u f a c t u r e r ' s claims, or are capable of supplying the clinician with the reliable data needed. Therefore, the l a b o r a t o r y a n a l y s t must continue to choose carefully from among the available commercial products. Since the advent of r e g u l a t o r y control of medical devices in Canada, there has been a s h i f t of emphasis in our own l a b o r a t o r y away from the d i r e c t evaluation of kits and associated i n s t r u ments t o w a r d the development of reference methods. The l a t t e r can then be used to assign t a r g e t values to serum pools which are then d i s t r i b u t e d to clinical l a b o r a t o r i e s across Canada for the v o l u n t a r y monitoring not only of the p e r f o r m a n c e of in vitro diagnostic products but all routine methods in use. This is a
137
p a r t i c u l a r l y useful means of checking the accuracy of procedures and, when results of such surveys show t h a t a considerable bias is associated with a method or a kit procedure in a n u m b e r of laboratories, the l a b o r a t o r y d i r e c t o r may well consider changing to a more accurate method. Studies involving the application of reference methods are under way and a r e p o r t of our f i n d i n g s for calcium, magnesium and c r e a t i n i n e procedures has already been presented'SL ACKNOWLEDGEMENT
The authors would like to t h a n k all the l a b o r a t o r y directors and t h e i r s t a f f who by t h e i r response to the questionnaire made this study possible. They are also indebted to Maurice Loshuk for his valuable assistance in the p r e p a r a t i o n , mailing and processing of the questionnaires. REFF-,RENCES
1. Logan, J. E. (1972). Crit. Rev. Clin. Lab. Sci., 3: 271289. 2. Logan, J. E., Renton, H. M., and Allen, R. H. (1970). Cli~. Biochem., 3: 81-89. 3. Weatherburn, M. W., and Logan, J. E. (1976). Clin. Biochem., 9: P6, #3.
