24/09/041 sir and the management of cancer trial data kate motohashi gray cancer institute,...
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SIR and the Management of Cancer Trial DataKate Motohashi
Gray Cancer Institute, Northwood, UK
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Introduction
BCON Trial Coordinator/ Data Manager since May 2001
Biology background with no experience of databases!
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Topics of Discussion
Background to the trial The database Retrieval of data Restructuring of the database Some questions
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A MULTICENTRE RANDOMISED PHASE III TRIAL OF RADIOTHERAPY WITH CARBOGEN AND NICOTINAMIDE IN THE TREATMENT OF LOCALLY ADVANCED BLADDER CANCER TRIAL PI: Prof Peter HoskinTRIAL STATISTICIAN Prof Søren Bentzen
Funded by the Cancer Research UK
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BCON
Bladder cancer Carbon dioxide 2%
Oxygen 98% Nicotinamide
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Bladder Cancer
~ 4% of all cancers in UK
UK incidence 2000: 11 080 (with just over two-thirds men)
Peak incidence in 7th decade
History of smoking/ exposure to chemicals
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Treatment of bladder cancer Surgery
1.Transurethral resection (TUR)
2.Total cystectomy
Chemotherapy
Radiotherapy
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Overall 5 year survival after RT
T2, T3 &T4 (muscle invasive): 5-40%
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Reasons for RT failure Intrinsic cell radio-resistance Tumour repopulation during RT Resistant cells due to HYPOXIA
HYPOXIA: the reduction of the O2
supply to tissue below physiological levels
- O2 is crucial for RT success
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Aim of BCON Trial
To address the problem of hypoxia by addition of the hypoxia modifying agents, carbogen and nicotinamide
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CARBOGEN: 02 (98%) and C02 (2%)
Oxygenation of the tumour is increased when cabogen is breathed
NICOTINAMIDE: amide of vitamin B3
Improves perfusion by reducing closure of blood vessels
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Phase II study at MVH
30 patients received carbogen alone 32 patients received CON
When compared to historical data significant gains were observed in
Local tumour control Disease-free survival Overall survival
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BCON Trial
Control arm
RT alone
Experimental arm
RT plus CON
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Endpoints of BCON Trial Tumour response at 6 months Local-failure free survival* Overall disease specific survival Treatment related morbidity* Quality of Life*
* Requiring ability to store records at different time-points
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330 patients over 4 years
Recruitment started Nov 2000
Target Accrual (to detect 15% improvement in local control)
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Why SIR?
SIR 2000 or SIR 2002?
Good at handling clinical data where patients have multiple visits
Compatibility with SPSS
Old Forms Developed with colour, ‘if’ clauses, width
definitions etc Allow double data entry
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Design of database Case orientated – patient number
Schema modelled on Case Report
Forms
Multiple records for morbidity data,
cystoscopy results and QoL
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Grade 1 Grade 2 Grade 3 Grade 4 Grade at end of week:1 2 3 4 5 6 8 12
Anorexia Loss of appetite Oral intake significantly decreased
Requiring IV fluids Feeding tube/parenteral nutrition required
Nausea Able to eat Oral intake significantly decreased
No significant intake, requiring IV fluids
Vomiting 1 episode in 24 hours over pre-treatment
2-5 episodes in 24 hours over pre-treatment
> 6 episodes in 24 hours over pre-treatment or need for IV fluids
Requiring parenteral nutrition, or physiologic consequences requiring intensive care; haemodynamic collapse
Dehydration Dry mucous membranes and/or diminished skin turgor
Requiring IV fluid replacement (brief)
Requiring IV fluid replacement (sustained)
Physiologic consequences requiring intensive care; haemodynamic collapse
Diarrhoea Increase of < 4 stools/day over pre-treatment
Increase of 4-6 stools/day or nocturnal stools
Increase of > 7 stools/day or incontinence; or need for parenteral support for dehydration
Physiologic consequences requiring intensive care; or haemodynamic collapse
Rectal bleeding
Mild without transfusion or medication
Persistent, requiring medications (eg. steroid suppositories) and/or break from radiation treatment
Requiring transfusion Catastrophic bleeding requiring major non-elective intervention
Haematuria (in the absence of vaginal bleeding)
Microscopic only Intermittent gross bleeding, no clots
Persistent gross bleeding of clots, may require catheterization or instrumentation, or transfusion
Open surgery or necrosis or deep bladder ulceration
Example of Weeks 1 to 12 symptom recording
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Maximum per case Total in database
CIR 1 253
PERSONAL 1 253
PRETREATMENT 1 253
TREATMENT 1 202
EARLY MORBIDITY 100 1434
LATE MORBIDITY 100 505
QOL 100 815
BIOPSY 1 175
RIP 1 71
CYSTECTOMY 1 15
CYSTOSCOPY 100 452
RECURRENCE/METASTASIS 1 60
PROTOCOL DEVIATION 1 11
SERIOUS ADVERSE EVENT 100 14
Record types
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Retrieval of data Accrual status Dumping to SPSS Follow-up status CRF compliance Reimbursement status Data verification/ error-checking Compliance to Nicotinamide
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Hospital No. of Patients enteredMount Vernon 67Velindre, Cardiff 34Christie, Manchester 30Derbyshire Royal, Derby 29Nottingham City Hospital 21Weston Park,Sheffield 15Oldchurch Hospital, Romford 13Cookridge Hospital, Leeds 12Bristol 9Newcastle 7Ipswich 6Kent & Canterbury 5Clatterbridge 5Royal Sussex County, Brighton 0Total number of patients 253
Participating centres
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RecruitmentCumulative accrual
113
186
253
130
330230
0
50
100
150
200
250
300
350
Oct-
02
D
ec-0
2
Feb-0
3
Apr-0
3
Jun-
03
Aug-0
3
Oct-
03
Dec-0
3
Feb-0
4
Apr-0
4
Jun-
04
Aug-0
4
Oct-
04
nu
mb
er o
f p
atie
nts
Actual
Target
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CRF status (Dec 2003)
CRF/visit %REC
Pre-treatment 94
Treatment 91
Early morbidityWeek 1 91Week 2 91Week 3 91Week 4 91Week 8 88Week 12 88
Late morbidityMonth 6 81Month 9 77Year 1 74Year 1.5 66Year 2 80Year 2.5 60
CRF/visit %REC
CystoscopyMonth 6 77Year 1 71Year 1.5 61Year 2 72Year 2.5 70
Quality of lifePre-treatment 85Week 4 80Week 12 69Month 6 64Year 1 51Year2 36
NUMBER REC % RECBiopsy samples 138 74
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0 no tumour 1 > 50% reduction 2 < 50% reduction 3 progression 4 recurrence after complete
remission 5 new superficial cancer
Old cystoscopy gradings
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New cystoscopy gradings
0 no tumour 1 superficial 2 muscle invasive
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Cystoscopy results in database
3 5 9 ze ro g ra d esd o w n lo a d ed in to e xce l
b a tch loa d ed
6 4 n o n-ze ro g ra d esre -g ra d ed
e n te red m an u a lly
N e w C ysto sco p y R e co rd c re a ted
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1. Missing Values Up to three values can be specified
which are missing values for the variable. Missing values are excluded from statistical procedures and functions.
BCON Database Missing Values BLANK = not available (ever) ‘9’/ ‘99’/ ‘999’ etc = not available (yet)
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RETRIEVAL.PROCESS CASES ALL. PROCESS REC NEWCYST. GET VARS TUMSTATE. IFTHEN (EXISTS (TUMSTATE) EQ 0) WRITE PATNO. ENDIF. END PROCESS REC.END PROCESS CASEEND RETRIEVAL
This retrieves field with missing value but doesn’t distinguish between different categories of missing values
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2. Wild card searches
Using search mode in forms and % for unknown characters
E.g. ‘F%W%’
Can it be done with PQL?
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3. Editing Log
Journalling – logs changes to the database
Is it possible to create a log where person editing data is prompted to give a reason for the change?
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Acknowledgements
Prof Søren Bentzen Prof Peter Hoskin Dr Francesca Buffa Trial centre contacts