RATE
48
VOLUME
70.1
ml
Out[192]=
VOLUME
VTBI
Opt1 Opt2 Opt3
UP up
Run
dn DN
Bolus Mute
Hold Options
Pressure
OnOff
1
2
3
4
1292 pages
“beautifully written introduction to
design of algorithms”
“the bible of the field”
“best textbook ever seen”
“We do not address
error-handling”
methods for assessing and
monitoring patient safety risks
5
6
assessing
monitoring
1. random low-level checks
3. logs are unreliable
2. make recipes for evaluation
7
8
discoveries
error and misplaced liability
4. number entry is unreliable
HAROLD THiMBLEBY
5. out by ten errors can be halved
6. improvements in safety can be embedded
9
10
11
12
Denise Melanson
22 August 2006
!!!!!!!!!!!!!!!!Root Cause Analysis
!
!
Fluorouracil Incident Root Cause Analysis
Final Draft: April 5, 2007
Final Formatted Report: April 30, 2007
Formatted for Web Posting: May 22, 2007
!
!
!
stopping rule
!
!
Institute for Safe Medication
Practices Canada®
Institut pour l’utilisation sécuritaire
des médicaments du Canada®
13
14
European Patent EP0264080, 1992
One object of the present invention is to provide novel 5-fluorouracil
derivatives which are useful as carcinostatic substances having high activity
but less toxicity. Another object of the present invention is to provide novel
5-fluorouracil derivatives which cause less side effects such as disorders in
the digestive tracts and autonomic imbalance. Accordingly, the present
invention provides a novel derivative of the formula wherein R1 is a group of
the formula: -(CH2)h -CH(R!)-CF3 wherein R! is hydrogen or a C1-C4
aliphatic group, and h is an integer of 0 to 4; a group of the formula: -CH2(CR32)i-CHF2 wherein R3 is hydrogen or fluorine, and i is an integer of 0 to
5; or a group of the formula: -(CH2)j -CHF(R4) wherein R4 is hydrogen or
methyl, and j is an integer of 1 to 4 since they have large therapeutic indexes
(TI) and/or causes less autonomic imbalance. Preferred examples of the
group R1 are
-CH2CF3, -(CH2)2CF3, -(CH2)3CF3, -(CH2)4CF3, -(CH2)5CF3,
-CH2CH(CH3)CF3, -CH2CH(C2H5)CF3, -CH2CH(C3H7)CF3,
-CH2CH(C4H9)CF3, -(CH2)2CH(CH3)CF3, -CH2CHF2, -(CH2)2CHF2,
-(CH2)3CHF2, -(CH2)4CHF2, -(CH2)5CHF2, -(CH2)4CH2F and
-(CH2)4CHFCH3.
15
16
European Patent EP0264080, 1992
One object of the present invention is to provide novel 5-fluorouracil
derivatives which are useful as carcinostatic substances having high activity
but less toxicity. Another object of the present invention is to provide novel
5-fluorouracil derivatives which cause less side effects such as disorders in
the digestive tracts and autonomic imbalance. Accordingly, the present
invention provides a novel derivative of the formula wherein R1 is a group of
the formula: -(CH2)h -CH(R!)-CF3 wherein R! is hydrogen or a C1-C4
aliphatic group, and h is an integer of 0 to 4; a group of the formula: -CH2(CR32)i-CHF2 wherein R3 is hydrogen or fluorine, and i is an integer of 0 to
5; or a group of the formula: -(CH2)j -CHF(R4) wherein R4 is hydrogen or
methyl, and j is an integer of 1 to 4 since they have large therapeutic indexes
(TI) and/or causes less autonomic imbalance. Preferred examples of the
group R1 are
-CH2CF3, -(CH2)2CF3, -(CH2)3CF3, -(CH2)4CF3, -(CH2)5CF3,
-CH2CH(CH3)CF3, -CH2CH(C2H5)CF3, -CH2CH(C3H7)CF3,
-CH2CH(C4H9)CF3, -(CH2)2CH(CH3)CF3, -CH2CHF2, -(CH2)2CHF2,
-(CH2)3CHF2, -(CH2)4CHF2, -(CH2)5CHF2, -(CH2)4CH2F and
-(CH2)4CHFCH3.
5250 mg
45.57 mg/mL
4 days
17
5,250 mg
(4 days x 24 hours per day)
45.57 mg per mL
18
US population
306,900,000
!"#$ 5250÷45.57÷(4!24) =
!"#$5250÷45.57÷4÷24 =
World population
6,707,000,000
!"#$!%&#$!%&#$4!24 !%'()*$
!"#$5250÷45.57÷!%&#$ =
AC 306900000 ÷ 6707000000 = 0.4575816
0.04575816
19
20
calculators are used by people
who don’t know the answers
and therefore can’t spot any errors
21
Press 1.2.3
Casio HS8V, HS85
Graseby 3400
Mathematica
Abbott
Microsoft Word 2008 v12.1.7
1.23
1.3
1+2 3
0.36
1/0 !Zero Divide
999, 123, 1.2, 1:23AM, 1:23PM
Excel
0
Word
1.5
22
1.2.3 1.5
24
23
24
user error
detects 2 types
of error
ignores every
other type of
error
bad result
25
25
26
detects 35 types
of error
H. Thimbleby, “Ignorance of interaction programming is killing people,”
ACM Interactions, pp52–57, September+October, 2008
27
28
… Think of a dose
… Say, 1.2
… Make keying errors
… Enter 1.2 12. 0.2 etc
… Classify out-by-ten errors
29
30
Normal
ADE probability
!at ! "10"
0.8
0.7
0.6
0.6
0.5
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0.4
0.4
0.3
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0.6
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31
0.0
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1.0
e
32
328
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33
34
35
36
Royal Society for the Prevention of Accidents
37
38
39
40
implications
• Some “correct” numbers
• Some
• Logs
are wrong
slips will be undetected
will be incorrect
• Users
are made liable for design errors
• Good
design improves everybody regardless of training