Volume 47, No, 10, July 2011
`
`yf fic val | surnal
`
`PeMeo:
`European journal Gf cancer
`v.47 no 10 ‘July 2011
`General Coilection
`am Cligvoe:
`Wit EU/2BA
`2011-08-02 06 47 49
`
`ISSN 0959-8049
`
`EUROPEAN JOURNAL OF CANCER
`
`IN THUS TISSU1
`
`trials of moleculartargeted therapies:
`Phase 1
`Are weevaluating toxicities properly?
`The
`preclinical
`and
`clinical
`activity
`aviscumine: A potential anticancer drug
`Effect. of celecoxib on survival
`in_ patients
`with advanced non-small cell lung cancer
`
`of
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`PROPERTY OF THE
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`GSEQRIC
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`EuROPEAN
`CaNnCER
`ORGANISATION
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`Genome & Co. v. Univ. of Chicago
`PGR2019-00002
`UNIV. CHICAGO EX. 2060
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`European Journal of Cancer
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`Aims and Scope
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`The European Journal of Cancer (including LIC Supplements) is an international cormprehensive oncology journal (hat publishes original
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`

`

`Volume 47i
`
`European Journal of Cancer
`
`Contents
`
`Editorial comment
`
`Phase 1 trials of molecular targeted therapies: Are we evaluating toxicities. properly?
`).-C. Sona
`
`Short communication
`
`Motor vehicle exposure and risk of oesophageal adenocarcinoma
`). Lagergren, C. Jansson and Y. Lu
`
`Reviews
`
`The preclinical andclinicalactivity of aviscumine; A potential anticancer drug
`H. Zwierzina,L. Bergmann,H.Fiebig, S. Aamdal, P, Schéffski, K. Witthohn and H.Lentzen
`
`Critical review of economic evaluations in multiple myeloma; An overview of the economic evidence and quality of the
`methodology
`J.G. Gaultney, W.K. Redekop, P. Sonneveld and C.A. Uyl-de Groot
`
`Clinical oncology
`Heterogeneity in the definition of dose-limitingtoxicity in phase I cancer clinical trials of molecularly targeted agents: A
`review of the literature
`C. Le Tourneau, A.R.A. Razak, H.K. Gan,S, Pop, V. Dieras, P. Tresca and X.Paoletti
`
`Extended schedule, escalated dose temozolomideversus dacarbazinein stage IV melanoma:Finalresults of a randomised
`phaseIll study (EORTC 18032)
`PM.Patel, S. Suciu, L. Mortier, WH. Kruit, C, Robert, D, Schadendorf, U, Trefzer, C.),A. Punt, R. Dummer, N. Davidson, J. Becker,
`R. Conry, J.A. Thompson, W.-, Hwu, K. Engelen, $.S. Agarwala, U.Keilholz, A.M.M. Eggermont and A. Spatz, on behalf of the EORTC
`Melanoma Group
`
`A phaseI studyofsirolimus and bevacizumabin patients with advanced malignancies
`E.E.W. Cohen, M.R. Sharma, L. Janisch, M.Llobrera, L. House, K. Wu, J, Ramirez, G.F. Fleming, W.M. Stadler and MJ. Ratain
`
`Reasonsgiven bypatients for participating, or not, in Phase 1 cancertrials
`5. Catt, C. Langridge, L. Fallowfield, D.C. Talbot and V. Jenkins
`
`A randomised phaseII trial of 1 month versus 1 yearof adjuvant high-doseinterferon 1-2b in high-risk acral melanoma
`patients
`L. Mao, L.Si, Z. Chi, C. Cui, X. Sheng, S. Li, B. Tang and J. Guo
`
`Adherenceto national guidelines for treatment and outcomeof endometrial cancerstage | in relation to co-morbidity in
`southern Netherlands 1995-2008
`D, Boll, R.H.A. Verhoeven, M.A. van der Aa, M.L.M. Lybeert, J.W.W. Coebergh and M.L.G. Janssen-Heijnen
`An open-label, multicentre biomarker-oriented AIO phase II trial of sunitinib for patients with chemo-refractory advanced
`gastric cancer
`M. Moehler, A. Mueller, J. Hartmann, M.P. Ebert, S.£. Al-Batran, P. Reimer, M. Weihrauch, F. Lordick, T. Trarbach,S, Biesterfeld,
`M. Kabisch, D. Wachtlin and BR. Galle,
`the German Arbeitsgemeinschaft Internistische Onkologie (AIO)
`
`Printed by Polestar Wheatons Ltd, Exeter, UK
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`One-monthrelative doseintensity of not less than 50%predicts favourable progression-free survival in sorafenib therapy
`for advancedrenalcell carcinomain Japanese patients
`A. Kawashima, H. Takayama,Y. Arai, G. Tanigawa, M. Nin, J. Kajikawa, T, Imazu, 7. Kinoshita, Y. Yasunaga, H. Inoue, K. Nishimura,
`S. Takada, K, Nishimura, A. Tsujimura and N. Nonomura, The Osaka RenalCell Carcinoma Clinical Study Collaboration
`
`Primary breast cancerpatients with high risk clinicopathologic features have high percentages of bone marrow epithelial
`cells with ALDHactivity and CD44°CD24"" cancer stem cell phenotype
`J.M. Reuben, BN, Lee, H. Gao, E.N. Cohen, M. Mego, A. Giordano, X. Wang, A. Lodhi, S. Krishnamurthy, G.N, Hortobagyi,
`M, Cristofanilli, A. Lucci and W.A. Woodward
`
`Peritumoural vascular invasion: A major determinantof triple-negative breast cancer outcome
`R. Sabatier, J. Jacquemier, F. Bertucci, B. Esterni, P. Finetti, F, Azario, D. Birnbaum, P. Viens, A. Goncalves and J.-M. Extra
`
`Effect of celecoxib on survival in patients with advanced non-small cell lung cancer: A double blind randomisedclinical
`phaseIll trial (CYCLUS study) by the Swedish Lung Cancer Study Group
`A. Koch, B. Bergman, E. Holmberg, C. Sederhalm,L. Ek, J. Kosieradzki, K. Lamberg, L. Thaning, 5,-0. Ydreborg and S. Sorenson,
`On behalf of the Swedish Lung Cancer Study Group
`
`Paediatric oncology
`Pharmacokinetics of cyclophosphamide and its metabolites in paediatric patients receiving high-dose myeloablative
`therapy
`G. Chinnaswamy, J. Errington, A. Foot, A.V. Boddy, GJ. Veal and M, Cole
`
`Epidemiology and cancer prevention
`Couples’ communication before the wife’s death to cancer and the widower'sfeelings of guilt or regretafter the loss - A
`population-based investigation
`].M. Jonasson, A. Hauksdottir, S. Nemes, PJ. Surkan, U. Valdimarsdattir, E. Onelov and G, Stemeck
`
`Adding familial risk assessmentto faecal occult blood test can increasethe effectiveness of population-based colorectal
`cancer screening
`N. Dekker, L.G.M. van Rossum, M. Van Vugt-van Pinxteren, S.H.C. van Stiphout, R.P.M.G. Hermens, W.A.G. van Zelst-Stams,
`M.G.H. van Oijen, R.).F. Lahetj, ).B.M,. Jansen and N. Hoogerbrugge
`
`Experimental oncology/Translational research
`Efficacy of a leptin receptor antagonist peptide in a mouse modelof triple-negative breast cancer
`L. OtvosJr., 1. Kovalszky, M. Riolft, R. Ferla, J, Olah, A. Satodola, K. Nama, A. Molino, Q. Piubello, J.D. Wade and E. Surmacz
`
`p62/SQSTM1involved in cisplatin resistance in human ovarian cancercells by clearing ubiquitinated proteins
`H.Yu, J. Su, ¥. Xu, J. Kang, H. Li, L. Zhang, H. Yi, X. Xiang,
`Liv and L. Sun
`
`VEGF-SPECT with '''In-bevacizumabin stageIII/IV melanoma patients
`WB. Nagengast, M.N. Lub-de Hooge, E.M.E. van Straten, 5. Kruyff, A.M. Brouwers, WEA. den Dunnen, J.8. de Jong, H. Hollema,
`R.A. Dierckx, N.H. Mulder, E.G.E, de Vries, HJ. Hoekstra and G.A.P. Hospers
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`eore ir
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`Sa a
`ELSEVIER
`
`Indexed/Abstracted in:
`Current Conterits;
`EMBASE/Excerpta Medica;
`Index Medicus; MEDLINE;
`CABS, BIOSIS Database;
`PASCAL-CNRS Database; CINAHL’
`
`ce
`ISSN.0959-8049
`
`

`

`
`‘This material maybe protected byCopyrightlaw(Title 17 U.S. Code}
`
`
`
`
`LUROPEAW JOUKNAL OF CANCER 47 (201T) C490 Lads
`
`available at www.sciencedirect.com
`
`-
`“es” ScienceDirect
`
` acer
`journal homepage: www.ejconline,com
`
`
`
` eeF
`ELSEVIER
`Ln
`
`Reasonsgiven by patients for participating, or not,
`in Phase 1 cancer trials
`
`S. Catt *", C. Langridge “, L. Fallowfield °, D.C. Talbot ”,V. Jenkins “
`* CR-UK Psychosocial Oncology Group, Brighton and Sussex Medical School, UK
`" Department of Medical Oncology, Churchill Hospital, University of Oxford, Oxford, UK
`
`ARTICLE [INFO
`
`ABSTRACT
`
`Article history:
`Received 7 January 2011
`Received in revised form 23 February
`2011
`
`Accepted 25 February 2011
`Available online 30 March 2011
`
`
`Keywords:
`Cancer
`Phase 1 trials
`Motivation
`Reasons
`Communication
`
`Trial participation
`
`Background: Gommunication with patients contemplating Phase 1 cancertrial participation
`can be challenging, Controversy exists as to whether they are provided with sufficient
`information to give genuinely informed consent. We present data examining the reasons
`patients pave for trial entry.
`Method: Following discussions with oncologists about Phase! trials, participants completed
`a 19-item study specific ‘accept or decline measure’ exploring hope, expectations of benefit,
`altruism, concerns, and general perceptionsof the trial information. They also completed 2
`standardised questionnaires measuring psychological morbidity and predisposition
`towards optimism.
`Results: Forty patients completed the study questionnaires. Patients were generally opti-
`mistic with few concerns about
`the experimental nature of Phase 1
`trials. Most 36/40
`(90%) consented totrial entry. Fifty-one percent thought the trial was the only treatment
`option available, The four main reasons for trial entry were: expectation of some medical
`benefit (21%): trial the best available option (21%); to maintain hope (15%) and to help with
`researeh (13%), Only one patient gave altruism as their main reasonfortrial participation.
`Conclusion Patents considering Phase 1 trials may be a self-selected group with optimistic
`expectations of personal benefit diving trial entry rather than altruism. Achieving genu-
`ely informed consent and avoidanee of
`therapeutic misconceptions in such patients
`toay be difficult
`
`w) 2011 Elsevier Ltd. All nghts reserved.
`
`—KRRKR
`1,
`Introduction
`
`A systematicreview by ‘Todd and colleagues” examined the
`positive and nepative attitudes of patients with advanced
`Phase 1 (P1) clinical trials are crucial in the devel ponent of
`cancer towards researeh, In this review 11 studies were iden-
`hew anti-cancer treatments. New agents that have shown
`tified for evaluation, Most
`involved hypothetical scenarios
`promise in the laboratory are Usually tested in patients with
`and only two were with patients in Pl tials~one qualitative?
`advanced disease. The aimsof Fl trials are to determine sale
`and one quantitative.” Common motives for participation
`dosage range and identify side-effects. These trials convey
`werealtruism, hope, and for personal benefit, Concerns about
`small prospects oftherapeutic benefit and carry varying pos
`negative impact on symptoms and risk of mereased hospital
`sibilities of side-effects,'
`It
`is therefore not surprising that
`admissions emerged as reasons for declining: participation,
`recruiting patients into these studies generates ethical de-
`Most patients were positive in general about research despite
`bate and creates challenging communicationissues,’
`having advanced disease. Conclusions were that more
`
`* Corresponding author: Address: Cancer Research UK Psychosocial Oncology Group, Brighton and Sussex Medical School, University ol
`Sussex, Falmer, Brighton, East Sussex BN1 9QG, UK. Tel.: +44 1273 873024; fax: 444 1273 873022
`E-mail address: S.L.Catt@sussex.ac.uk (5. Catt).
`0959-8049/% - see front matter «©: 9011 ElsevierLtd, All rights reserved.
`doi:10.1016/j.ejca.2011.02.020
`
`

`

`
`
`the experiences and
`research was still warranted to elicit
`opinions of patients who have either apreed, or declined, to
`participate in early phase trials.
`We found 8 studies where in Pl cancer trials reasons lor
`participation had been recorded and these are summarised
`
`in Table 1.
`Both qualitative and quantitative studies have
`reached similar conclusions as to why patients participate.
`Although primarily motivated by hopes for improvements in
`their condition, other reasons expressed include: appeasing
`relatives and friends, a desire to contribute to the progress
`of medicine,
`trust
`in the clinician, and a sense that there
`was ‘no other option’. Altruism:
`is commonly quoted as a
`key driver
`for
`trial entry, but these studies show it
`is infre-
`quently named by patients as a primary motivating factor.
`Understanding why patients participate or not in P1 trials
`could assist
`the development of communication training
`courses for specialists working within the area and aidtrial
`recruitment. The difficulties encountered with discussing
`Phase3 (P3) cancer clinical trials have been well documented
`and recommendations made for healthcare professionals
`B
`q
`y
`communication skills
`training.!"'’ Subsequently
`suitable,
`successful, courses dealing with recruiting patients to P3 tri-
`als have been developed and evaluated.’’ Nevertheless,
`it
`arguably requires even higher order communication skills to
`talk to patients about P1 trials.'" °°
`Healthcare professionals are often dealing with vulnerable
`patients for whom most conventional treatments have failed
`and who may come to the consultation with unrealistic
`expectations for benefit. Patient factors contributing to this
`situation include demography, previous treatment experi
`ences, personality traits and current physical and mental
`health, Recent meta-analysis"' confirms that one-third of
`patients with cancerin acute care suffer mental health prob-
`lems that warrant appropriate treatment and this prevalence
`is above that
`of
`the general population. The
`levels of
`depression and anxiety disorders for patients with advanced
`cancerin palliative care match or often exceed those in acute
`care,’
`Personality traits mayalso influence health decision-mak-
`ing so are of interest whenlookingat factors affectingtrial
`recruitment, especially optimism, The benefit of positive
`thinking is a notion often applied to health/illness and cance!
`by lay people and somehealthcare professionals. In their re-
`view Scheier and Carver’ state the effects of optimism are
`not limited to making peoplefeel better, it also confers posi-
`tive influences on what people do and what peopleare able to
`achievein times of adversity. It seems reasonable therefore to
`pay attention to optimism when trying to understand the
`decisions patients with advanced cancer make about P1 tral
`participation.
`in this descriptive paper we focus on the reasons patients
`gave for accepting ordeclining the invitation to participate in
`Pt trials, their psychological well-being and predisposition tao-
`wards optimism.
`
`2.
`
`Methods and materials
`
`The data were collected as part of a larger CRUK funded
`study”?
`to improve communication between healthcare
`
`trustin),helpothers(33%),familypressure
`
`
`
`),trustintrialdoctor(70%),
`
`
`
`
`
`
`trialcentre(67%),trustinreferringdoctor(63
`
`,nobetteroption(8
`
`
`Therapeuticbenefit(100%)
`
`
`
`Open-endedinterview
`
`
`Structuredinterview
`Rodenhuisetal.°(Netherlands)
`Daughertyetal.*(USA)
`
`
`
`
`
`Hopeofbenefit,appeaserelatives,contributetoresearch,nootheroption
`
`
`
`n
`
`Design
`
`Article
`
`
`
`esata
`
`‘able1-Summaryofp
`
`yemeterteoriegA
`
`ri
`=|
`[=]ro
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`#0t
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`=]5
`=]Lat
`=I
`av
`my
`2
`
`
`
`
`
`
`
`tyCe)trmeyable
`
`
`
`
`
`
`
`Personalbenefit(70%),helpothersorcontributetoresearch(22%),ad (8%)Hopeofbenefit
`
`
`
`(toprank),nothingtoloseandhelpothers
`
`Trustindoctor(28%
`
`
`
`
`
`
`
`7
`2
`
`2
`3
`
`37
`
`2
`
`22 2
`
`10
`
`163
`
`
`
`Structuredinterview
`
`
`
`Structuredinterview
`
`Questionnaire
`
`
`
`Structuredinterview
`
`groupsQuestionnaire
`Focus
`
`
`
`Tomamicheletal.‘*(Switzerland)
`
`
`Itohetal.*°
`
`
`(Japan)Yoderetal.*'(USA)
`
`Schuttaetal.'*(USA)
`Agrawaletal.’(USA)
`Hutchison“(UK) ae
`
`
`
`CUNMOVP AN SOUNNAL OF CANCE 47 (p0tt) tago laggy
`
`1491
`
`
`
`
`
`
`
`),advisedbydoctor(22%),nootheroption(9%
`
`ism(6%)visedbydocto
`
`),alt°
`
`
`
`
`
`Reasonsforclinicaltrialparticipation
`
`
`
`
`
`9
`
`
`
`(30%),contributetoresearch(22%)
`
`6
`
`
`
`trustindoctor,positivedissociationwithaltruism
`
`
`
`
`
`dvisedbydocto
`
`nda
`
`a
`
`3)
`
`(equalmidrank),familypressure(bottomrank
`
`
`
`
`
`
`
`
`
`Hopeofbenefit,
`
`
`
`
`
`
`
`
`
`
`
`4),trustindoctor(26%),other-unspecifiedreasons(12%),
`
`Hopeofbenefit(597
`
`tor
`
`pressure(9%),doc
`
`
`
`
`
`fi
`
`amily
`
`
`
`
`
`
`
`Therapeuticbenefit-becausecancerisgrowing(75%),
`
`
`
`contributetoresearch(3%)
`
`|
`
`
`
`pressure(7%)
`
`

`

`1492
`
`ROPEAN TOUPRANAL UT CANE ER 47 (2011) l4g0 1497
`
`BU
`
`trials. The
`professionals and patients when discussing P1
`study had multi-centre ethical approval
`(Oxfordshire Re-
`search Ethics Committee C Ref: 07/Q1G606/20) and all
`local
`NHS R&D permissions.
`This was a convenience sample. To reduce the risk of
`introducing selection bias, whenever researchers were pres
`entall patients attending clinics for a P1 trial discussion were
`approached consecutively.
`Prior to consultations patients were given an information
`sheet about the communication study to read and writtenin-
`formed consent was obtained. The consultation was digitally
`audio recorded, after which the researchers conducted face
`to-face study specific semi-structured interviews with pa
`tients to determine patients’ perspectives on what the con-
`sultation had covered. Clinicians also completed a_ brief
`questionnaire probing their views on what had been dis
`cussed during the consultation. These data have been re-
`ported elsewhere.“” Additionally, patients were given 3
`questionnaires to complete at home and return by post after
`they had madedecisions about trial entry.
`
`2.1,
`
`Questionnaires
`
`The three questionnaires administered were, (1) clinical trial
`accept/decline questionnaire,
`(2) Life Orientation ‘Test-
`Revised (LOT-R),“* and (3) General Health Questionnaire-12
`item version (GHQ12).”"
`
` Accept/decline questionaire
`2.1.1.
`Patients’ motivations for trial participation or not, were re-
`corded via a study specific questionnaire (see Appendix A)
`which was based on a design by Penman and colleapues*”
`and from previous research on the reasons patients pave for
`joining Phase 3 trials.*’ The questionnaire consisted ofan ini-
`tial question ascertaining whether or not
`the patient had
`agreedto trial entry. Patients were then asked to rate on a
`5-point Likert scale to whal extent they apreed or disapreed
`with alist of 19 reasons. that mipht have influenced the deci
`sion to either accept or decline the trial uivitution ‘They indi
`cated the most important reason for thei decision and had
`the opportunity to add further explanations in an additional
`box (qualitative responses). No ftormal reliability tenting: of
`this questionnaireis available but it has been used in several
`previous studies. “"""
`
`LOT-R
`2.1.2,
`This 10-item self-report seale measures predisposition to
`wards optimism. Validity and reliability have been published
`and it has been applied in oncology settings. ' There ape six
`target statements (with an even mix of positive and nepative
`wording), and fourfiller items. Respondents rate their agree
`ment with items on a 5-point Likert scale ranging from
`0= strongly disagree to 4 = strongly agree. Higher scores rep
`resent greater optimism,
`
`GHQI12
`21.3,
`This is a well validated self-report measure of general psycho-
`logical well-being widely used in patient populations.” A
`score above a threshold of
`=4 is suggestive of probable
`psychological morbidity,
`
`2.2,
`
`Statistical analysis
`
`Using SPSS 16,0 for Windows summary statistics were pener-
`ated for the data: counts, percentages and averages, A non-
`parametric correlation, Spearman's rho, was used to test the
`relationship between psychological well-being and optimism.
`
`
`able 2 —- Characteristics of the whole study sample.
`
` (n = 40)
`Sex
`Male
`Female
`
`22 (55%)
`18 (45%)
`
`Age
`Mean(S.D.)
`Range (min-max)
`
`Age band
`25-34
`35-44
`45-54
`55-64
`>65
`Missing data
`Marital status
`Partner
`No partner
`Missing data
`
`Employed
`Yes
`No
`Missing data
`Education
`No school exams
`GCSE/A Level
`University and higher
`Missing data
`Cancer site
`
`Colorectal/upper Gl
`Breast
`Gynaecological
`Skin
`Other
`Previous treatments
`
`Surpery (ever)
`single intervention
`Multiple interventions
`Ghemotherapy (ever)
`Single course
`Multiple courses
`Radiotherapy
`Hormone
`
`Previous trial experience
`Yes
`Missing data
`GHO12
`Above threshold (case)
`Below threshold
`Missing data
`LOT-R scores
`Mean (S.D.)
`
`Range (min-max)
`
`58.8 (11.10)
`29-76 years
`
`3 (8%)
`1 (3%)
`& (20%)
`15 (38%)
`12 (31%)
`1
`
`28 (72%)
`11 (28%)
`1
`
`9 (23%)
`30 (77%)
`1
`
`13 (33%)
`12 (31%)
`14 (36%)
`1
`
`22 (55%)
`6 (15%)
`5 (13%)
`3 (8%)
`4 (10%)
`
`32 (80%)
`20 (50%)
`12 (30%)
`38 (95%)
`7 (17%)
`41 (78%)
`12 (30%)
`2 (5%)
`
`18 (46%)
`|
`
`19 (49%)
`20 (51%)
`|
`
`15.45 (3.62)
`8-24
`
`

`

`
`
`3.
`
`Results
`
`3.1.
`
`Sample
`
`Recruitment look place from five UK cancer centres (Beatson
`Oncology Centre, Glasgow; Royal Marsden Hospital, Sutton,
`Royal Free Hospital, London, Southampton and Oxford CR-
`UK Medical Oncology Units), between August 2007 and
`December 2008
`
`A total of 58 out of 62 patients approached and invited to
`join the communication study” consented, Of
`these seven
`did not return questionnaires, five were subsequently ineligi-
`ble for trials, four only had general trial discussions, one with-
`drew, and one came fora follow-up visit, Data were therefore
`available for 40 participants.
`Table 2? gives a summary of socio-demographic and other
`charactenstics, and Tuble 3 specifics of the trials discussed.
`A Spearman's rho test for the LOT-R scores and GHO1? cases
`shows a sipnificant correlation (~0.341 at
`the 0,05 level,
`2-tailed, n=39, one patient did not complete the GHOI?
`measure), with lower optimism associated with caseness for
`probable psychological morbidity.
`
`able 3 - Trial specifics.
`
`(n = 40)
`
`‘Type of trial discussion
`General discussion
`Doseescalation study
`Targeting/antibody/immunotherapy
`Combination (standard chemo plus new agent)
`
`12 (30%)
`LO (25%)
`|
`L (27.5%)
`7 (17.5%)
`
`k
`
`a7 (2011) 1490 age
`
`1493
`
`Overall, 36/40 (90%) patients accepted entry into Pl clinical
`trials, Only 4/40 (10%) declined, a number too small for any
`statistical analysis, These decliners' characteristics are dis-
`
`their decision are pre-
`played in Table 4. Explanations for
`sented below as full quotes from the qualitative responses
`given on the accept/decline questionnaire. The explanations
`given include quality of
`life considerations, other treatment
`options, and time constraints.
`
`3.2.
`
`Qualitative responses given by trial decliners
`
`ID 16. Been living on my own. Nowback with my husband
`and moving back to Wales to make the most of whatever time
`I have lett.
`
`ID 20. Quality of life is far more important than quantity of
`life,
`
`| decided to become a private patient and have a drug
`ID 44.
`not available on the NHS for a few months. As to whether this
`was of benefit, | would re-consider a trial if offered at a later
`date and assuming the drug! am taking is unsuccessful. Time
`will tell.
`
`ID 60. Decided that this particular trial was very intense and
`thatthetravelling would put toogreat a strain on both myself
`and my husband. There's another trial in August which is not
`so intense which hopefully will work in the same way but
`with fewer visits.
`
`Trial agent
`None discussed (general discussion)
`Cytotoxic and/or antiproliferatve
`Monoclonal antibody
`Tyrosine kinase inhibitor
`Angiogenesis inhibitor
`DNA repair inhibitor
`Vaccine
`Other
`
`Route of administration
`None discussed(general discussion)
`Oral only
`Intravenous only
`Intramuscular only
`Intravenous and oral
`Unspecified
`
`‘able 4 - Decliner characteristics.
`
`12 (30%)
`5 (12.5%)
`3 (7.5%)
`7 (17.5%)
`4 (10%)
`5 (12.5%)
`2 (5%)
`2 (5%)
`
`12 (30%)
`12 (30%)
`9 (22.5%)
`2 (5%)
`4 (10%)
`1 (2.5%)
`
`3.3.
`
`Reasons for trial entry
`
`to each state-
`Table 5 displays the frequency of agreement
`ment on the accept/decline questionnaire expressed in per-
`centages. The categories ‘strongly agree’ and ‘agree to some
`extent’ were combined. The majority of patients (97%) agreed
`they had been provided with sufficient trial information, both
`oral (‘the doctor told me what | needed to know’) and written
`(I was given clear information to read’), Likewise 97% trusted
`the treating physician and wantedto help with research, and
`few (16%) felt unable to say no to the trial, A third of the pa-
`tients were ‘worried about being a guinea pig’. A few (16%)
`were concerned about the burdens associated with the tral.
`Three quarters thought
`they would derive some medical
`
`
`
`ID Sex Age (years) Marital status Employed
`Education
`Cancersite Trial type Previous
`LOT-R (total) GHQ12
`trial
`(case)
`
`66
`Married
`No
`No exams
`Stomach
`Phase 1
`Yes
`13
`1
`58
`Married
`Yes
`University
`Anal
`Phase 1
`No
`21
`2
`72
`Married
`No
`GCSE/Alevel
`Lung
`Phase 1
`No
`16
`2
`64
`Married
`
`No exams Bowel Phase 1 No 14No 8
`
`
`
`
`
`* Denotes. a case which is a score of»4 on the GHQ1? and is indicative of probable psychological morbidity
`
`16
`20
`44
`60
`
`F
`«=F
`M
`|
`
`
`
`

`

`1494
`
`RO
`
`Ma? (20TT) T490 tag?
`
`able 5 - Frequency of agreement to each statement on the accept/decline questionnaireforall patients (n= 39).
`Statement number
`
`Wording
`
`Number agreeing (%)
`‘strongly agree’ or ‘agree
`to some extent’
`
`
`
`38 (100)
`| knew that I could leave the trial at any time
`11
`38 (97)
`The doctor told me what I needed to know about the tral
`7
`38 (97)
`| trusted the doctor treating me
`8
`36 (97)"
`I was given clear informationto read about thetral
`9
`38 (97)
`[ wanted to help with the research
`15
`35 (90)
`I felt | had nothing to lose
`4
`33 (85)
`| thought thetrial was the best option available
`1
`33 (85)
`I thought joiningthe trial would give me hope
`3
`32 (82)
`I felt that others with my illness would benefit from the results of the trial
`17
`30 (77)
`[ thought the trial offered me some medical benefit
`5
`25 (66)
`1 thought thetrial offered more intensivefollow-up
`13
`23 (59)
`I was worried about the side-effects of the trial drup(s)
`6
`22 (56)
`The doctor wanted me tojoin thetrial
`18
`20 (51)
`[ thought thetrial was theonly optionavailable
`2
`20 (51)
`Others(e.g. family or friends) wanted meto join the trial
`19
`13 (33)
`| was worried about being a ‘guineapig’
`16
`6 (16)
`[ did notfeel able to say no/refuse
`12
`6 (16)
`| thought the trial needed too much effort from me
`14
`
`[ was not given enoughinformationto read aboutthe trial 5 (14)"
`10
`* One decliner did not complete a questionnaire.
`* n=37 for statements 9 and 10 dueto missingdata,
`" n= 38 for statements 11, 12, 13 and 14 due to missingdata,
`
`
`
`
`able 6 - The main reason given for joining the trial (n = 39).
`
`
`Statement number
`Wording
`
`Count of reason (%)
`
`
`I thought thetrial offered me some medical benefit
`5
`| thought thetrial was the best option available
`1
`! thoughtjoiningthe trial would give me hope
`3
`| wanted to help with the research
`15
`I thought thetrial was the only option available
`2
`| thought the trial offered more intensive follow-up
`13
`| was worried about beinga ‘guineapig’
`16
`| felt that others with my illness would benefit from the results of thetrial
`7
`! trusted the doctor treating me
`8
`[knew that
`| could leave the tnal at any time
`11
`* Onedecliner did not complete a questionnaire
`
`8 (21)
`8 (21)
`6 (15)
`5 (13)
`4 (10)
`3 (8)
`2 (5)
`1 (2)
`1 (2)
`
`1 (2)
`=
`
`=
`
`benefit andat leas