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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