Enhancing cancer clinical trial management: recommendations from a qualitative study of trial participants' experiences

PSYCHO-ONCOLOGY

Psycho-Oncology 9: 314–322 (2000)

ENHANCING CANCER CLINICAL TRIALMANAGEMENT: RECOMMENDATIONS FROM A

QUALITATIVE STUDY OF TRIALPARTICIPANTS’ EXPERIENCES

KAREN COX*Faculty of Medicine and Health Sciences, School of Nursing, Medical School, Uni6ersity of Nottingham, UK

SUMMARY

Using a qualitative approach, a total of 55 adult patients with advanced cancer were interviewed to examine theirperceptions of participating in early phase anti-cancer drug trials. Patients’ views and experiences were explored,primarily through the use of in-depth interviews, with additional information accessed through two widely-usedquality of life questionnaires, at the beginning of, during and after trial participation. The picture of trialparticipation established from this work suggests that it is a dynamic process, that has a different meaning andimpact according to the stage of trial involvement the patient is experiencing. The findings identify how patientsperceived the offer of the trial, dealt with the trial treatment, and came to terms with trial conclusion. The insightand understanding that this work provides in terms of the impact of trial involvement over time as well as detailsof patients’ information, decision-making and support needs has significant implications for cancer clinical trialmanagement. The recommendations put forward in this paper focus on acknowledging the contribution trialparticipants make to cancer research, enhancing the process of preparing patients for trial participation,recognizing the need for continuing care, the incorporation of patients and potential patients’ views into theclinical trials system, and educating the public about clinical trials. Copyright © 2000 John Wiley & Sons, Ltd.

INTRODUCTION

Clinical trials remain the standard route by whichnew techniques and drugs are evaluated for theireffectiveness, and are essential for assessing theeffects of health technologies, and for controllingfor the introduction of new therapeutic regimensinto the National Health Service in the UnitedKingdom (DOH, 1992). The evaluation of newdrug treatments in oncology involves a process ofsequential clinical trials from phase I to III. Theaim of which is to determine the safety and effec-tiveness of new compounds (Schwartsmann et al.,1991).

The nature of cytotoxic drugs and their poten-tial for mutagenicity and carcinogenicity severelylimits the volunteers on whom anti-cancer agentscan be tested. Anti-cancer agents at phase I and II

of testing are evaluated in patients with cancerwho cannot be cured by conventional methods,and have progressing, terminal disease. The na-ture of the patient group and the phase of testingmeans that the majority of those who take partgain no benefit whatsoever, with overall responserates being lower than 5% (Estey et al., 1986;Marsoni et al., 1987; Decoster et al., 1990). Evalu-ating new drug treatments in this situation, there-fore, raises complex ethical and practical prob-lems. Ethical concerns centre around humanrights and consent to research that will not be ofdirect benefit to the individual, and practical con-cerns relate to the continued need to recruit intothese studies in order that new treatments aredeveloped and evaluated (Cox, 1999a).

A balance is, therefore, required to ensure thatthe rights and needs of an individual participatingin a clinical trial are not over-ridden by the trialprocess. To achieve this, it is essential that theprocesses involved, such as recruitment, consent,decision-making, participation and follow-up, areacceptable to patients. The hearing, interpretingand acting on patients’ views is crucial to this

* Correspondence to: Faculty of Medicine and Health Sci-ences, School of Nursing, Post-Graduate Division, Room B50,Medical School, University of Nottingham NG7 2UH, UK.Tel.: +44 115 9709265; fax: +44 115 9709955; e-mail:[email protected]

Copyright © 2000 John Wiley & Sons, Ltd. Recei6ed 29 October 1999Accepted 15 May 2000

ENHANCING CANCER CLINICAL TRIAL MANAGEMENT 315

process. To date, work in this area is limited toquestionnaire studies of reasons for trial partici-pation (Kardinal and Cupper, 1979; Penman etal., 1984; Rodenhuis et al., 1984; Daugherty et al.,1995; Kass et al., 1996; Itoh et al., 1997), and tostudies which have used quality of life assessmenttools to assess the impact of trial involvement onparticipants’ quality of life (Moinpour et al., 1989;Melink et al., 1992; Aaronson et al., 1993; Adamsand Bissett, 1993). This approach has resulted inthe trial participants’ voice being largely ignored,and little being known about how patients makesense of the total experience of trial participation,from recruitment through to follow-up (Cox andAvis, 1996).

This paper presents the findings and recommen-dations from a study that sought to begin to fillthis gap through obtaining the views of 55 pa-tients, who took part in early phase anti-cancerdrug trials in a regional oncology centre. The aimof this study was to identify the psychosocialimpact of participating in these kind of trials, asexperienced by the patients themselves; it soughtto discover and interpret their ways of copingwith what was happening to them, and identifythe consequences of trial involvement. Local Re-search Ethics Committee approval was obtainedfor this work, as well as the permission of consul-tant oncologists to approach patients to take partin this study. The qualitative research approachutilized in this work allowed access to patients’experiences and the longitudinal design shifted thefocus of previous research from recruitment andinformed consent, to one that considered thewhole of the trial experience. This approach al-lowed exploration of participants’ views at thebeginning of, during and after trial participation,in their own terms.

PATIENTS AND METHODS

Patients offered participation in a phase I or IIanti-cancer drug trial, over a 12-month period,were invited to take part in an interview study oftheir trial experiences. Patients were interviewedand completed two questionnaires at four pointsduring the trial process. These were (1) as soon aspossible after making the decision to participate(usually 48 h), (2) after two cycles of the trialtreatment, (3) at the time of trial withdrawal orcompletion, and (4) 6–8 weeks after trial conclu-

sion. The semi-structured interviews consisted of aseries of broad open questions around recruitmentexperiences, information received, what they un-derstood about the trial, decision-making experi-ences, their reasons for trial participation, ex-perience of trial involvement, support neededthroughout the trial, the impact on their qualityof life, the meaning of trial participation, andtheir satisfaction with care received. This datacollection was supplemented with two previouslyvalidated quality of life questionnaires, the Eu-ropean Organization for Research and Treatmentof Cancer (EORTC) QLQ C-30 (Aaronson et al.,1993) and the Hospital Anxiety and DepressionScale (HADS) (Zigmond and Snaith, 1983). TheEORTC QLQ C-30 produces scores that repre-sent patients’ level of physical, role, social, cogni-tive and emotional functioning, and severity ofsymptoms. The HADS produces scores that rep-resent patients’ levels of anxiety and depression.Patients were interviewed in their own home or ina quiet room in the cancer centre. All interviewswere tape-recorded, transcribed and then codedand analysed, with the aid of the qualitative dataanalysis computer package NUD*IST (Non-nu-merical Unstructured Data Indexing, Searchingand Theorising) (Qualitative Solutions forResearch, 1995). All questionnaire responses werecollated using SPSS (Statistical Package for theSocial Sciences) for Windows. To assess changesin the scores obtained from the quality of lifequestionnaires from pre-trial to follow-up, theFriedmans non-parametric test for repeated mea-sures was performed using time as a factor(Kinnear and Gray, 1997).

RESULTS

A total of 55 patients were included in this study,22 men and 33 women. The mean age was 58.8years, with a range of 37–74 years. Over 70% ofthe patients were married. The majority of tu-mour sites were the common solid tumours, lung,breast and gastrointestinal. Forty per-cent hadnot received any treatment for their disease priorto the offer of the trial treatment. In addition, themajority of patients had been diagnosed for lessthan 12 months. All 55 patients had a pre-trialinterview. Thirty-five patients had a during trialinterview, five had died, two refused and 13 hadbeen withdrawn from the trial, and so, for these

Copyright © 2000 John Wiley & Sons, Ltd. Psycho-Oncology 9: 314–322 (2000)

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13, this interview was omitted, and they wentstraight to a post-trial interview. Thirty-seven pa-tients had a post-trial interview, 12 patients werenow dead and six refused to be interviewed. Atfollow-up, 27 patients were interviewed, 21 werenow dead and 7 refused to be interviewed. Intotal, 154 interviews were carried out and 306questionnaires were completed. In this paper, theinterview findings are briefly presented, followedby recommendations for enhancing trial manage-ment (for a more detailed discussion of the find-ings, see Cox, 1999b). The questionnaire data isnot included here, although readers may be inter-ested to note that there were no statistically signif-icant findings to report from analysis of thequestionnaire data.

Patients’ experiences of trial recruitment

Of the 55 patients included in this study, 22 hadreceived no prior therapy for their disease, andhad invariably been told there was no standardtreatment for their cancer. The 33 patients whohad received prior therapy had, in the majority ofcases, been told they were now untreatable be-cause of the recurrence of their disease. Thissituation meant that prior to the offer of trialtreatment, many patients experienced an increas-ing sense of feeling helpless and distressed. Theoffer of a trial treatment was, therefore, seen as aturning point for these patients, as one patientstates:

. . . they had told me I was untreatable which is themain part of the story really. Dr A said, ‘no I can’tdo anything for that but there is a study taking placein the chemotherapy department and it is possiblethey might be able to help you’. Y02 (pre-trial).

Thirty patients (54%) described the offer of thetrial as being ‘the light at the end of the tunnel’,because of the hope it offered. This includedhoping that the trial treatment would be a miraclecure, that it would be better than current treat-ments, that they might achieve relief of symptoms,and that they would live longer, as the followingpatient articulates:

We’ve got stuff in its experimental stage. I’m readingabout it everyday. You just can’t pick up a paper,you just can’t see a newscast—I mean one weekthere is going to be some good news about cancer,but it never seems to be there. So I thought if everthere was a chance that I could be one of thosepeople that they are experimenting on then, as I am

going to die anyway, I might as well have a crack atit, and I might be one of the ones that they say ‘andthis chap has lived another year and another year’Y38 (pre-trial).

Thirty-two (58%) patients described how theoffer of the trial generated uncertainty, and 30patients (54%) described how the trial offer madethem feel special, privileged, pleased, lucky andhonoured, because, as they described it, ‘not ev-eryone gets the chance to take part in somethinglike this’. For these patients, the trial was seen asa chance to help themselves and fight their dis-ease, as described by one patient in the quotebelow:

I didn’t want to withdraw into a cupboard and saythat’s it and not be a contributor. I suppose in a wayit’s a bit of an honour if you think you might havehelped. I mean the illnesses that I’ve had somebodymust have contributed some way scientifically overthe years to make things easier, to bring more knowl-edge to help me. So why don’t I do the same forsomebody else? Y32 (pre-trial).

With regard to patient involvement in decision-making, typically nearly 80% of these patientswanted the health-care professionals to presentthem with all the information, and then advisethem what to do. Indeed, the majority interpretedthe offer of the trial treatment as being the rightthing for them to accept, because it was what thedoctor had offered. The quote below is typical ofpatient responses in relation to involvement indecision-making:

They told us to go away and think about it. Well wehad already discussed the probabilities before wewent that we would be offered some form ofchemotherapy and I was quite clear that whateverwas recommended or advocated by the consultantthat would be the course of action. If the consultantwas telling us that this new drug, although it wasn’tlicensed, was the most suitable we would go aheadwith it, we didn’t need to leave the building to dothat. Y01 (pre-trial).

Just over 70% of the group also described howthey had information about the clinical trial pre-sented to them in a positive way, both verballyand in the clinician’s manner. In addition, all 55patients recalled being given written informationabout the trial they had been offered, with justover half of the patients stating it acted as areference for them when they returned home.However, in response to the question ‘how wouldyou describe what it is you were asked to be



involved in?’, only 16 patients were able to de-scribe the purpose of the trial they had beenoffered. This is a similar finding to that of Daugh-erty et al. (1995), who noted that in their study ofpatients’ understanding of the purpose of the trialthey had given consent to, only a third of thesample were able to state the purpose of the trial.Subsequent reading ease assessments (Flesch,1948) of the patient information sheets found thatonly one out of the nine analysed fell into therange of being easy to read and, therefore, under-stand. This may have been a contributory factorin the lack of understanding expressed by thepatients in the present study.

Patients’ reasons for accepting trial participa-tion included the desire to be in expert hands(54%), to help others (52%; this usually encom-passed future cancer patients, cancer research andthe doctors who were involved in the research),that they felt they had no choice (36%; essentiallyif they wanted to live they had to do something),and that they had nothing to lose (23%; becausethey were going to die anyway). Similar reasonshave been identified in previous studies (Penmanet al., 1984; Daugherty et al., 1995; Kass et al.,1996; Itoh et al., 1997).

Patients’ experiences of trial participation

As patients progressed through the trial, discus-sion of their experiences reflected an increasingsense of being burdened by trial involvement in allcases. This burden consisted of dealing with theside-effects of the trial treatment, and the addi-tional demands placed on them through being in atrial. Additional demands ranged from frequenthospital visits for blood tests, electrocardiograms(ECGs), x-rays, scans, hospital stays for bloodtransfusions or antibiotics, problems with carparking, long distances to travel, side-effects ofthe trial drug, quality of life questionnaires, fa-tigue, dealing with changing hopes, and the uncer-tainty of outcome. What was also clear was thatthe majority of these trial burdens were unantici-pated by patients at the beginning of their trialtreatment.

Dealing with these physical and emotional bur-dens often led patients to question why they wereputting themselves through the trial in the firstplace, and whether it was all worthwhile. Patientstalked about how, initially, they saw the benefitsof taking part in the trial outweighing any harm

they may be caused. As patients progressedthrough the trial and received information abouttheir response to the trial treatment (invariablystable disease or progression), a feeling that theharm was too great, and a sense of disillusion-ment with what was on offer took over, this canbe clearly seen in the quote below:

I am frightened I am not going to be able to makethe course. It’s been alright coming until these lastcouple of times and I shouldn’t feel like this becausethe results have been so good for me—you know the[tumour] shrinkage has been great. I should be feel-ing more encouraged than I am. I don’t know. It’sgot to be a real drag coming here. Y15 (during trial).

However, despite these thoughts, all but one ofthe patients interviewed at this time said theywould rather persevere than stop the trial andhave to deal with the fact that there was nothingelse for them. In addition, the responsibility forstopping trial participation was seen by thesepatients as resting with the doctor.

During these second interviews, 26 out of the35 patients interviewed talked about the meaningtrial participation held for them. These includedbeing in expert hands, having a purpose for theirlives, and living a life on hold. Being in experthands was obviously important to this group ofpatients, as it was a feature associated with whythey accepted trial involvement in the first in-stance. Patients talked about feeling special be-cause of the amount of attention they werereceiving, felt they were getting the best possiblecare, were being monitored, had access to special-ist equipment, and were special because of theirposition of being in a trial. As one patient states:

I feel a bit—I suppose—a bit special, in a way,because I have had the chance to be on it. Plus youthink you are getting this extra attention while youare on it. I think because it’s a study you know youare going to have the best really, you know, ratherthan just being one of the others. Y08 (during trial).

For many patients, trial participation also gavethem a purpose in their lives (16 out of 35). Thispurpose was expressed in terms of doing some-thing and not giving up, helping self and others,and contributing to cancer research through theirefforts. This again echoes the findings presentedearlier, when patients described how the offer oftrial participation gave them a feeling of self-worth, and the opportunity to take part in some-thing they saw as being worthwhile. However,when patients talked about how they were dealing


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with trial involvement, their talk also reflectedhow they were living a life on hold, and that thetrial had become the main focus in their lives, asillustrated in the quote below:

We can’t plan anything. I just feel as though I’m notin control of my life at all. All I see is hospitals,white coats and nurses. Week in and week out.Never free from going to that hospital. I walk in andI think, ‘I hate this hospital’. Y44 (during trial).

Trial participation demanded an investment oftime, emotional and physical energy from patientsand families, that meant other aspects of theirlives were effectively put on hold for the durationof their trial involvement.

Patients’ experiences of trial conclusion andfollow-up

Trial conclusion occurred when either a patientcompleted the full number of cycles of treatment(usually four or six), or was withdrawn from thetrial. In this study, 70% of those interviewed werewithdrawn from the trial they were taking part in.This withdrawal was usually a result of toxicity ofthe treatment and/or disease progression. At thistime, patients expressed a sense of disappointmentthat the trial drug had not been successful, and afear of being abandoned, as illustrated in theinterview extract below:

K What has actually struck you most about finish-ing being in the drug study?

R I think the sense of disappointment, that’s thebiggest thing. I think I am disappointed that I amnot going to be able to continue with it and [yet also]relief that in one way I have not got to have it againbecause it might have made me so ill. But no, thebiggest thing is disappointment definitely. Y34 (post-trial).

The disappointment expressed by these patientsappeared to relate to the fact that the high hopesthey had at the beginning of the trial were notrealized. Disappointment that the new drug ortreatment regime had not worked, combined withthe burden of trial participation, meant that trialconclusion was a distressing time for this group ofpatients.

Fear of being abandoned was a feature of allthe interviews at trial conclusion and at 6-weeksfollow-up. During the post-trial interviews, pa-tients talked about the desire to maintain theintensity of attention that they received while on

the trial, as well as contact with the trial’s nurses,in particular. As patients moved into the follow-up phase after trial conclusion, this fear of beingabandoned was even more acute, and patientstalked about still wanting to be kept an eye on,that they felt they had lost a safety line, andincreasingly felt the professionals had given up onthem, for example:

I still get a nagging feeling, you know I’m having notreatment, so what is going to happen, and have theygiven up and those sort of things. Y14 (follow-up).

Despite the fact that patients talked about feelingdisappointed with the clinical outcome, actuallytaking part in the trial was, overall, seen as apositive thing to have done. Even though manypatients talked about the lack of clinical benefitand the trial burden they had experienced, thiswas seen to have not been in vain because theyhad been given a chance to try something new, tohelp themselves and to help others. Altruism,which appeared to be a motivating factor in pa-tients’ acceptance of the offer of trial treatment,also appeared to persist throughout the course oftrial involvement. Indeed, 21 out of the 27 pa-tients interviewed at follow-up said they wouldmake the same decision to participate. Four pa-tients, however, said they probably would notaccept trial participation again, as they would beapprehensive about accepting the burden associ-ated with trial involvement, while two patientsremained undecided.

One of the interesting findings related to trialconclusion was the increasing importance patientsplaced on asking for feedback on the trial theyhad taken part in. As one patient said:

I’d like to know how they [other patients] are doingand how it’s progressing and the other ladies afterme . . . how they are and whether or not its beensuccessful, whether they’ve got the right dose sortedout, you know. I assume they are still increasing it.Y16 (follow-up).

This request for information seemed to be toenable them to establish the contribution they hadmade to cancer research, and establish for them-selves a meaning for their trial involvement.

DISCUSSION

There are no easy answers to the ethical andpractical problems that these early trials raise.



What this research does, however, is highlight thepatients’ perspective, and in doing so, has uncov-ered elements of the trial experience that havepreviously remained hidden, that have implica-tions for clinical practice. Using this insight, thisdiscussion seeks to suggest five ways in which thepatients’ perspective revealed by this research maybe used to inform clinical trial management.

Acknowledging participants’ contributions

An interesting finding from this research relatesto the apparent desire of patients to contribute tocancer research. The language of altruism was aprominent feature in the majority of interviewswith these patients, and remained so throughoutthe course of trial involvement. While it would benaı̈ve to assume from this that altruism was aprimary motivation in patients’ desire to partici-pate in clinical trials—indeed, the findings in thisresearch seem to suggest that it was secondary tothe hope that the trial treatment might be amiracle cure—the desire to help others by con-tributing to cancer research nevertheless appearsto be a powerful motivation. At the recruitmentstage, this apparent altruism was expressed in theway patients talked about feeling honoured by theoffer of trial participation, and the opportunity totake part in something which would not only helpthemselves but future patients, health-care staffand cancer research. During trial participation,the sense of purpose that involvement in theclinical trial gave patients sustained many ofthem, and helped them to deal with the burdensof trial involvement. However, it was also clearthat these patients were never really sure aboutthe nature or extent of their contribution. Thisbecame apparent at trial conclusion, when pa-tients were told that the trial drug was not bene-fiting them in terms of disease control. At thistime, they expressed the hope that they had stillcontributed to something worthwhile, but theyoften appeared not to be assured of this in anyway. During interviews, patients and carers oftenrequested information about whether the trial hadbeen worthwhile. What this and previous work inthe field, such as Kardinal and Cupper (1979) andCassileth et al. (1982), tells us is that patients arenot only generally willing, but also actively wishto participate in clinical trials in order to con-tribute to science and society. This aspect of trialparticipation, however, is rarely mentioned inconsent procedures.

Altruism needs to be supported, and the contri-bution patients make through trial involvementshould be acknowledged and fed-back, as it ap-pears to give a sense of purpose and meaning topatients at the end of their lives. The search formeaning appears to have an important role in theprocess of adaptation within the context of lifethreatening situations (Turnquist et al., 1988).Research in this area suggests that an individual’sability to search for and find a meaning in theirillness and treatment may have a significant im-pact on psychosocial well-being, and adjustmentto the impact of cancer on their lives (Lewis, 1989;Luker et al., 1996). Feedback may be one waythat on-going psychosocial support for these pa-tients can be offered, and the contribution madethrough their trial participation acknowledged.Possible ways this can be achieved is for patientsand their families to receive reports on the find-ings of the research to which they have con-tributed, maybe even with an invitation tocomment. This could be extended to evening orafternoon discussion sessions, where informationabout the trial could be discussed with patients,their families and carers. Further work is neededto establish the most appropriate mode of deliveryand content of any feedback strategy.

Preparing patients for trial participation

It was clear that patients did not fully under-stand what they were taking on when they made adecision to participate in the clinical trial in termsof the benefits and consequences of trial participa-tion. Initially, patients saw the benefits of trialparticipation as being the chance of an extratreatment, a chance to prolong their life and hopeof a miracle cure. However, the benefits thesepatients actually experienced were not what theyhad initially expected, and at trial conclusion,patients had to deal with the fact that their initialhopes remained unfulfilled. In addition, patientswere coping with the consequences of trial partic-ipation, such as the side-effects of the trial drug,and the additional demands that being in a trialgenerates, but which were largely unanticipatedby these patients.

Drawing these findings together suggests thatthose recruiting patients into early trials have anobligation to inform patients of what the ‘real’benefits of participation might be. These real ben-efits were identified in this study in terms of a


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sense of purpose, a feeling of self-worth, and anopportunity to contribute to cancer research in avery real way, although the benefit in terms ofany tumour response is likely to be limited. In thisway, the possibility that patients are consciouslyor unconsciously coerced into participation withthe promise of false hope may be diminished, ascan the later problem of having to deal with thedisappointment that the trial drug had not beenthe miracle cure they were hoping for. In addi-tion, there is a need for patients to be informed ofthe burdens of trial involvement, so that they arefully aware of what is being demanded of thembefore they agree to participate. Giving patientsthis kind of information means they will be betterinformed about what they are actually taking onwhen they agree to participate, and be better ableto deal with what is happening to them through-out the trial process.

Providing patients with information, however,is a challenging area. Both verbal communicationand patient information leaflets were identified inthis study as problem areas, because of the fram-ing of information and problems with readability.Consideration needs to be given to ways ofproviding accurate and straightforward informa-tion to those who are being asked to take part inclinical research. The use of video, audio-tapesand interactive computer programmes may be justsome of the ways forward in this area of commu-nicating information, combined with a system ofchecking understanding and on-going educationand training in communication skills for health-care staff. Work is already being undertaken inthis field for example Fallowfield et al. (1998).

Enhancing continuity of palliati6e care

Trial conclusion resulting from withdrawalfrom the trial because of disease progression ordrug toxicity was a common feature of trial in-volvement for the patients in this study. Indeed, astaggering 37 out of 55 patients were withdrawnfrom their trial because of either of these tworeasons. Trial withdrawal and conclusion was adeeply distressing and stressful time for patients;in addition to having to confront their own illnessand/or lack of response to their last hope of‘cure’, they also experienced decreased contactfrom the unit. At this time, patients articulated afear of being abandoned and of being left withoutsupport. It was also at this point that patientsbegan to talk about dying and their own death.

These findings suggest that those managingthese early trials need to acknowledge that thepatients they are dealing with are dying and,therefore, need support during and beyond thetrial to deal with this. Recognition needs to begiven to the fact that actual trial involvement is asmall part of the overall health-care experience ofthese individuals, but that, while being small, itcan cause a major disruption to the overall dyingtrajectory (Glaser and Strauss, 1968). One waythese issues could be addressed is to consider earlyclinical trials in the context of a programme ofcontinuing palliative care and support, wherethere is recognition of the fact that the duty ofcare owed to these patients and carers extendsbeyond trial involvement, and needs to addressissues around death and dying. It is also impera-tive that community staff, to whom patients arelikely to be referred at trial conclusion, such asGPs, district nurses, Macmillan nurses and hos-pice staff, also understand the nature of clinicaltrials, and are supportive of patients’ participa-tion. By acknowledging the need for palliativecare and ‘death-work’ (Schou, 1993), and ensur-ing appropriate follow-up care, some of the prob-lems the patients in this research experienced attrial conclusion, such as feeling abandoned andthat there was nothing more that could be done,may be avoided. One way this could be achievedis for staff to rotate a unit from the researchsetting throughout, to areas where standard treat-ments are offered, through to the palliative careprovided in the hospice setting. In addition, fur-ther research is required to establish the mostappropriate and effective way to follow-up thoseindividuals who have participated in a cancerclinical trial.

Accessing the trial participants’ and potential trialparticipants’ 6iew

Patients need to continue to be consulted abouttheir trial experiences. Their views need to beincorporated into trial processes to ensure that themanagement of the trial is acceptable and appro-priate. Patients’ and carers’ views can provide avaluable insight into clinical care, and health-careexperiences, that those who are providing care ona daily basis cannot see, and in turn, this kind ofinformation can help us find new ways of workingthat better meet patients’ expressed needs. In ad-dition, patients need not only the right to choose



whether to participate in a trial or not, but alsothe right to influence which choices are availablein the first place. Work is already taking place inthis area; Bradburn et al. (1995), for instance,have used patient focus groups as a way of incor-porating patients’ views into a clinical trial designof follow-up after treatment for breast cancer.Involving patients, potential patients and the re-search community in this way could result inmajor changes in the procedures by which re-search protocols are initiated, the site of researchtrials, criteria for entry into trials, end points fortrials and the definition of the overall researchagenda. There is a need to mobilize and engagewith public opinion, and ensure that special inter-est groups—such as consumers, carers and re-searchers—have a voice, and that their views aretaken into account (Baum, 1993). This kind ofapproach has already been effective in the field ofHIV and AIDS research related to the emergenceof HIV and AIDS activism in the US during the1980s. In the US, patients are now playing agreater role in the design and evaluation of clini-cal trials, as well as setting the research agenda(Annas, 1989; Palitiel, 1993). In addition, thisapproach has also led to a constant evaluation ofwhich groups of individuals are participating intrials (Stone et al., 1997), a consideration of howto engage under-represented groups in AIDS tri-als (Ickovics and Meisler, 1997), and the develop-ment of alternative trial designs which meetpatients’ needs of rapid access to new therapies(Green et al., 1990).

Increasing public understanding of clinical trials

Finally, clinical trials methodology is difficultto understand. In addition, medical uncertainty asto the most appropriate treatments is difficult formany patients to come to terms with. The teach-ing of these concepts, particularly when peopleare well, may help individuals to appreciate uncer-tainty, and realistically assess the difficulties anddilemmas in treating disease efficiently, success-fully and economically. A person educated in thisway is empowered, and in a much better positionto evaluate a particular trial being proposed anddiscuss the options more intelligently (Baum,1993; Thornton, 1994). Recently, the NationalCancer Institute (NCI) in the US has begun anactive effort to educate patients and the publicabout clinical trials (NCI, 1998). The development

in the US of the Cancer Information Service hasbeen an important information resource for thepublic, as has the physician’s data query (PDQ)system, which provides rapid access to informa-tion about on-going clinical trials for patients andphysicians. In the UK, organizations such as Can-cer Bacup (British Association of Cancer UnitedPatients) provide telephone support and informa-tion to patients and their carers. However, theseservices reach only a limited number of relativelyempowered patients. New ways need to be devel-oped to reach a larger general public. Incorpora-tion of these ideas into a health education/awareness programme, or an aspect of the schoolcurriculum, may be just a couple of the waysforward.

In conclusion, while the data presented heremay not necessarily be representative of otherpatients’ experiences, the qualitative nature of thestudy has revealed a vast amount of rich anddetailed information on the experience of trialinvolvement, from the participants perspective,which has not previously been examined. In thisrespect, it highlights important areas of clinicalpractice that could be improved in order that thetrial experience for patients in the future is moreacceptable, based on real life experiences, opin-ions and perceptions. In this way, the balancereferred to earlier, of ensuring that the rights andneeds of an individual participating in a clinicaltrial are not over-ridden by the trial process,could begin to be achieved.

ACKNOWLEDGEMENTS

Thanks are due to Professor James Carmichael (CRCAcademic Department of Clinical Oncology, Universityof Nottingham) and Professor Veronica James (Schoolof Nursing, University of Nottingham) for their super-vision of this project. This research was funded by theCancer Research Campaign (grant no. CP 1037/0101),and undertaken while the author was Cancer ResearchCampaign Nursing Research Fellow at the Universityof Nottingham.

REFERENCES

Aaronson NK, Ahmedzai S, Begman M, Cull A. 1993.The European Organisation for Research and Treat-ment of Cancer QLQ-C30: a quality of life instru-ment for use in international trials in oncology. J NatCancer Inst 85(5): 365–376.


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Adams L, Bissett D. 1993. Quality of life assessment ina phase I study. Eur J Cancer 29A(Supplement 6): 259.

Annas GJ. 1989. Faith healing hope and the FDA: thepolitics of AIDS drug trials. Villano6a Law Re6 34:771–797.

Baum M. 1993. New approach for recruitment intorandomised controlled trials. Lancet 314: 812–813.

Bradburn J, Maher J, Adewuyi-Dalton R, Grunfeld E,Lanchaster T, Mant D. 1995. Developing clinical trialprotocols: the use of patient focus groups. Psyco-oncol-ogy 4: 107–112.

Cassileth BR, Lusk EJ, Miller DS, Hurwitz S. 1982.Attitudes towards clinical trials among patients and thepublic. J Am Med Ass 248(8): 968–970.

Cox K. 1999a. A means to an end? A study of patients’experiences of participation in phase I and II anti-can-cer drug trials, Unpublished PhD Thesis. University ofNottingham.

Cox K. 1999b. Researching Research: patients’ experi-ences of participation in phase I and II anti-cancer drugtrials. Eur J Oncol Nurs 3(3): 143–152.

Cox K, Avis M. 1996. Ethical and practical problems ofearly anti-cancer drug trials: a review of the literature.Eur J Cancer Care 5(2): 90–95.

Daugherty C, Ratain M, Grochowski E, Stocking C,Kodish E. 1995. Perceptions of cancer patients and theirphysicians involved in phase I trials. J Clin Oncol 13(5):1062–1072.

Decoster G, Stein G, Holdener E. 1990. Responses andtoxic deaths in phase I clinical trials. Ann Oncol 1:175–182.

Department of Health (DOH). 1992. Assessing the effectsof health technologies: principles, practice, proposals.Advisory Group on Health Technology Assessment forthe Director of Research and Development, London,Department of Health.

Estey E, Hoth D, Simon R, Marsoni S. 1986. Therapeuticresponse in phase I trials of anti-neoplastic agents.Cancer Treat Rep 70(9): 1105–1113.

Fallowfield L, Lipkin M, Hall A. 1998. Teaching senioroncologists communication skills: results from phaseI of a comprehensive longitudinal program in theUnited Kingdom. J Clin Oncol 16(5): 1961–1968.

Flesch R. 1948. A new readability yardstick. J ApplPsychol 32: 221–233.

Glaser BG, Strauss AL. 1968. Time for Dying. Aldine:Chicago.

Green SB, Ellenberg SS, Finkelstein D. 1990. Issues inthe design of drug trials for AIDS. Controlled ClinTrials 11(2): 80–87.

Ickovics JR, Meisler AW. 1997. Adherence in AIDSclinical trials: a framework for clinical research andclinical care. J Clin Epidemiol 50(4): 385–391.

Itoh K, Sasaki Y, Fujii H. 1997. Patients in phase I trialsof anti-cancer agents in Japan: motivation, comprehen-sion and expectations. Br J Cancer 76(1): 107–113.

Kardinal CG, Cupper HT. 1979. Hope, consent andclinical research. Forum Med 1(8): 48–49.

Kass NE, Sugarman J, Faden R, Schoch-Spana M. 1996.Trust. The fragile foundation of contemporary biomed-ical research. Hastings Centre Rep 26(5): 25–29.

Kinnear PR, Gray CD. 1997. SPSS for Windows MadeSimple (2nd edn). Psychology Press: East Sussex.

Lewis FM. 1989. Attributions of control, experiencedmeaning, and psychosocial well-being in patients withadvanced cancer. J Pyschosoc Oncol 7: 105–110.

Luker K, Beaver K, Leinster SJ, Owens RG. 1996.Meaning of illness for women with breast cancer. J Ad6Nurs 23: 1194–1201.

Marsoni S, Hoth D, Simon R, Leyland-Jones B. 1987.Clinical drug development: an analysis of phase IItrials, 1970–1985. Cancer Treat Rep 71(1): 71–80.

Melink TJ, Clark GM, Von Hoff DD. 1992. The impactof phase I clinical trials on the quality of life of patientswith cancer. Anti-cancer Drugs 3: 571–576.

Moinpour CM, Feigl P, Metch B. 1989. Quality of lifeendpoints in cancer clinical trials: review and recom-mendations. J Nat Cancer Inst 81: 485–495.

National Cancer Institute (NCI). 1998. Patients HelpingProgress: Cancer Clinical Trials. Department of Healthand Human Services, National Institutes for Health:Bethesda, Maryland, USA.

Palitiel AD. 1993. The epidemiological and economicconsequences of AIDS clinical trials. J AIDS 6:179–190.

Penman DT, Holland JC, Bahna GF. 1984. Informedconsent for investigational chemotherapy. Patients’and physicians’ perspectives. J Clin Oncol 2: 849–855.

Qualitative Solutions for Research. 1995. Non-numericalUn-structured Data Indexing Searching and Theorising,NUD.IST. Version 3.06 for Windows. Sage Publica-tions: London.

Rodenhuis S, Van Den Heuvel WJ, Annyas AA, KoopsHS. 1984. Patient motivation and informed consent ina phase I study of an anti-cancer agent. Eur J CancerClin Oncol 20(4): 457–462.

Schou KC. 1993. The awareness contexts and the con-struction of dying in the cancer treatment setting: microand macro levels in narrative analysis. In The Sociologyof Death, Clarke D (ed.). Blackwell: Oxford; 238–263.

Schwartsmann G, Wanders J, Koier IJ. 1991. EORTCnew drug development office co-ordinating and mon-itoring programme for phase I and II trials with newanti-cancer agents. E J Cancer 27: 1162–1168.

Stone VE, Mauch MY, Steger K, Janas SF, Craven DE.1997. Race, gender, drug use and participation in AIDSclinical trials. Lessons from a municipal hospitalcohort. J Gen Int Med 12(3): 150–157.

Thornton H. 1994. The dilemmas of randomisation andequipoise from the viewpoint of a patient invited toparticipate in a breast cancer trial. CERES News 11(2):3–4.

Turnquist D, Harvey J, Anderson B. 1988. Attributionsand adjustment to life-threatening illness. Br J ClinPsychol 27(1): 55–65.

Zigmond AS, Snaith RP. 1983. The hospital anxiety anddepression scale. Acta Psychiatr Scand 67: 361–370.


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Enhancing cancer clinical trial management: recommendations from a qualitative study of trial participants' experiences