Barriers to participation in clinical trials of cancer: a ...

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Barriers to participation in clinical trials of cancer: a meta-analysis and systematic review of patient-reported factors ARTICLE in THE LANCET ONCOLOGY · MARCH 2006 Impact Factor: 24.73 · DOI: 10.1016/S1470-2045(06)70576-9 · Source: PubMed

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Available from: Dugald Seely Retrieved on: 21 July 2015

Articles

Barriers to participation in clinical trials of cancer: a metaanalysis and systematic review of patient-reported factors Edward J Mills, Dugald Seely, Beth Rachlis, Lauren Griffith, Ping Wu, Kumanan Wilson, Peter Ellis, James R Wright

Summary Background Enrolling participants onto clinical trials of cancer presents an important challenge. We aimed to identify the concerns of patients with cancer about, and the barriers to, participation in clinical trials. Methods We did a systematic review to assess studies of barriers to participation in experimental trials and randomised trials for validity and content. We estimated the frequency with which patients identified particular issues by pooling across studies that presented data for barriers to participation in clinical trials as proportions. Findings We analysed 12 qualitative studies (n=722) and 21 quantitative studies (n=5452). Two qualitative studies inquired of patients who were currently enrolled onto clinical trials, and ten inquired of patients who were eligible for enrolment onto various clinical trials. Barriers to participation in clinical trials were protocol-related, patientrelated, or physician-related. The most common reasons cited as barriers included: concerns with the trial setting; a dislike of randomisation; general discomfort with the research process; complexity and stringency of the protocol; presence of a placebo or no-treatment group; potential side-effects; being unaware of trial opportunities; the idea that clinical trials are not appropriate for serious diseases; fear that trial involvement would have a negative effect on the relationship with their physician; and their physician’s attitudes towards the trial. Meta-analysis confirmed the findings of our systematic review. Interpretation The identification of such barriers to the participation in clinical trials should help trialists to develop strategies that will keep to a maximum participation and cooperation in cancer trials, while informing and protecting prospective participants adequately.

Introduction

Methods

As a main cause of death in the developed world, cancer will affect nearly half of all men, and a third of all women in their lifetimes.1 In North America, about 1·3 million cancer diagnoses were predicted in 2005, with 1500 people a day dying from the disease. Advances in patient care need rigorous scientific research, including thorough testing of an intervention in the setting of a clinical trial to ensure treatment efficacy and safety. The success of these trials depends mainly on keeping the number of individuals recruited onto the study to a maximum and the number of dropouts to a minimum.2 However, a limiting factor in the advances of patient care has been inadequate accrual for clinical trials. Estimates of participation in cancer trials have ranged to as low as 2–3% overall, and representation from paediatric, minority ethnic, and elderly groups is even lower.3,4 An understanding of the underlying concerns behind low patient accrual is necessary to increase participation in clinical trials. Researchers have attempted to identify the barriers to enrolment by questioning individuals eligible for participation in clinical trials of cancer. A systematic review5 has assessed such barriers to participation in elderly patients with cancer. We aimed to do a systematic review to define barriers to participation in clinical trials within all patient groups, using content-analysis techniques and particularly focusing on qualitative and quantitative data.

Search strategy and selection criteria

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We did a systematic search for all qualitative studies and quantitative studies that addressed the attitudes and barriers of patients to participation in clinical trials of cancer. Through use of open-ended questions or semi-structured interviews, qualitative studies allow for an unlimited number of participant responses. By contrast, quantitative surveys follow a more structured methodology, limiting the number of responses possible. With the aid of an information specialist (PR), EM and BR searched the following databases independently, in duplicate: AMED (from 1985); Campbell Collaboration (from 2001); CinAhl (from 1982); Cochrane library (from 1998); Embase (from 1990); ERIC (from 1966); MEDLINE (from 1966); and NHS EED (from 1975). The upper search limit was Nov 29, 2005, for all databases. Unpublished studies were also sought by use of the Clinicaltrials.gov website and the UK national research register. Our search strategy combined terms that represented attitudes, barriers, and anxieties. Our search vocabulary was: “cancer” or “oncol*”; “clinical trials”; “barriers”; “participat*”; and “enrol*”. EM, DS, and BR supplemented this search by reviewing the bibliographies of key papers (ie, review papers). EM, DS, and BR assessed these studies for inclusion; no language restrictions were applied to the search.

Lancet Oncol 2006; 7: 141–48 Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada (E J Mills PhD, L Griffith MSc, P Ellis MD, J R Wright MD); Division of Haematology/Oncology, Hospital for Sick Children, Toronto, Canada (D Seely ND); Department of Clinical Epidemiology, Canadian College of Naturopathic Medicine, Toronto, Canada; (P Wu MSc, D Seely); Department of Health Care and Epidemiology, University of British Columbia, Vancouver, Canada (B Rachlis BSc); Department of Medicine, University of Toronto, Toronto, Canada (K Wilson MD); and Juravinski Cancer Centre, McMaster University, Hamilton, Canada (P Ellis, J R Wright) Correspondence to: Dr Edward J Mills, Department of Clinical Epidemiology and Biostatistics, McMaster University, HSC-2C12, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada [email protected]

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Randomised controlled trials

Non-randomised trials

Ref 10

14

Ref 15

7

100

●

● ●

n 41 Data transcribed verbatim* Predefined questions if interview Trained facilitator if focus group Mention of saturation Description of how research themes identified Participants’ answers reviewed for clarification Original data presented Findings analysed by more than one assessor

11

12

13

16

17

21

11

82

n 56

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60

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Combined studies 18

Ref 19

20

28

n 196

103

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21 17 ●

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*Use of audiotapes, videotapes, or fieldnotes.

Table 1: Characteristics of qualitative studies’ methods on barriers to participation in clinical trials of cancer

BR and EM independently reviewed the abstracts. If reviewers disagreed, the full article was obtained and assessed. Eligible studies met the following criteria: reported an original research study; contained content addressing patient-identified barriers to participation in cancer clinical trials; and were a semi-structured interview, focus-group study, or survey of patients with cancer. We excluded studies that addressed only participant descriptions and patient demographics, and vaccine trials.

Data abstraction and validity assessment BR and PW independently extracted data and appraised the validity and content. We determined the study populations, and defined phase III trials as randomised controlled trials, and phase I and II trials as experimental unless randomisation was stated explicitly. We characterised the content of the methods of the qualitative studies using a modified checklist designed to assess internal validity;6–9 quantitative studies were not scored. From an initial review of all studies, we developed iteratively a coding template to categorise key barriers to clinical-research participation. This template consisted of the mutually exclusive headings of: protocol-related barriers; patient-related barriers; and physician-related barriers, as determined subjectively by EM, BR, and DS. These reviewers did a second, independent analysis of the papers to identify whether they contained the barriers present in the template. Data were regarded eligible for inclusion in the meta-analysis only if the study reported proportions of respondents. We attempted to contact all authors of the quantitative studies to verify data interpretation.

Statistical analyses We measured chance-adjusted agreement between reviewers for eligibility using the statistic. When information on proportions of respondents was available from the study’s published paper or from the authors, we determined the weighted proportions of studies 142

(ie, the weighting of results according to sample size). We calculated an overall estimate of effect by combining the proportions in every study weighted by the inverse of their variances. We present the weighted mean, with 95% CI and lower CI cut at zero. Thus, larger studies with smaller variances have relatively more effect on the final estimate. Summary estimates of quantitative studies were calculated by use of a random-effects model, which recognised that the studies are a sample of all potential studies and which incorporated an additional between-study component to the estimate of variability. Heterogeneity between studies, which we expected as a result of different patient populations, duration of assessment, and type of trial in the analysis, was assessed by use of a test based on the 2 distribution with n–1 degrees of freedom, in which n was the number of studies.

Results The literature search identified 362 studies. There was excellent (=0·83) agreement between EM and BR on choosing the final 129 applicable studies from the reviewed abstracts. Of these studies, 96 were excluded because they were not original studies (n=33), did not survey patients (n=46), or did not assess barriers to participation in clinical trials of cancer (n=17). Thus, 33 studies were included in our analyses. There was perfect agreement on the final studies selected between BR and PW. Twelve studies were qualitative by design: table 1 shows the characteristics of the methods of these studies;10–21 table 2 shows the characteristics of the populations; and table 3 shows their findings.10–21 Four studies10,15,19,20 used focus groups (n=396), five11–13,16,21 used semi-structured interviews (n=116), and three14,17,18 used mainly open-ended questioning (n=210) to obtain barriers and attitudes. 2122–42 studies were quantitative, and used structured questionnaires or structured interviews (n=5452) to determine potential barriers (table 4). Of the http://oncology.thelancet.com Vol 7 February 2006

Articles

33 qualitative or quantitative studies, nine15-18,23,31,34,35,40 assessed barriers towards participation in experimental (ie, non-randomised) trials, 1610–14,24–30,33,36–38 reported barriers to participating in a randomised controlled trial, and eight19–22,32,39,41,42 studies did not specify the type of trial, or reported barriers to both experimental trials and randomised controlled trials and thus are included in a combined category. All studies were published in English and done in the USA, UK, Canada, or Denmark. Participation in clinical trial n=41; 20 women with breast cancer and 21 community members (no data for ethnic origin) n=60; 36 men and 24 women with colorectal cancer (no data for ethnic origin)

Never participated in a trial

Table 3 shows the themes presented in the 12 qualitative studies;10–21 table 4 shows the themes from the 21 quantitative studies.22–42 All qualitative studies reported barriers to participation that were protocolrelated (table 3). Other protocol-related barriers that affected decision-making included negative media attention surrounding the intervention,17 knowledge of the Tuskegee studies,12,15,16,20,21 and the potential for cancer recurrence.21

Main idea of study

To investigate knowledge and understanding of clinical research in women in the community and in women previously diagnosed with breast cancer 25 would participate in a To develop a method of defining attitudes trial; 35 would refuse towards the risks and benefits of treatments in a trial: to determine whether this method can detect a difference between attitudes held by those patients who would agree to trial participation and those who would refuse n=21 men with prostate 12 had refused trial To investigate patients’ perceptions of cancer (no data for ethnic randomisation, and 9 agreed randomisation, and understand their reasons for origin) to be randomised in a trial consenting to or refusing randomisation within a controversial trial of localised prostate cancer n=11 men with prostate No data for To assess differences in participation vs noncancer (no data for ethnic previous participation participation in a trial comparing external-beam origin) radiotherapy and cryotherapy n=82; 28 men and Eligible for trial entry To understand patient preferences and attitudes 54 women with cancer (no to help clinicians understand the concern of data for ethnic origin) individual patients before discussing randomisation into a trial n=56 men community Never participated in a trial; To assess qualitatively attitudes associated with members (all African 50% willing to participate willingness of African Americans to participate in American) clinical trials of prostate cancer n=7; 5 men and 2 women Agreed to trial participation To address barriers toward involvement in clinical with cancer (no data for trials with a focus on perspective of patient ethnic origin) n=100; 51 men and 79 (80%) would participate if To describe prospective participants’ initial source 49 women with cancer offered trial of information about, understanding of, and (83 white, 13 of other motivation to participate in a phase I trial of ethnic origin, and antiangiogenesis agent human recombinant 4 unkown) endostatin n=28; 6 men and One patient had participated Study discusses opinions of members of ethnic 22 women with cancer in a clinical trial of cancer groups regarding clinical-trial participation, in (8 African American, particular knowledge, benefits, and reasons for 10 Hispanic, and 10 non-participation native American) n=196 women with breast 3 African American and To assess barriers to participation in a treatment cancer (61 African 14 white patients had trial experienced by African American and white American, 135 white or participated in a clinical trial; women diagnosed with breast cancer other) 10% of African American patients vs 26% white patients would participate in a future trial n=103; 32 men and No data for willingness to To obtain information about perceptions of 71 women community participate or for previous clinical trials and barriers to participation in cancer members (all African participation research American) n=17; 2 men and Never participated in a trial To increase participation in clinical trials of 15 women with cancer patients with cancer who have low income and (all white) who live in rural areas: assessment of patients’ attitudes, knowledge, and beliefs regarding cancer clinical trials

Study setting

Group characteristics

Ref

Primary school or medical psychology unit

Women in community more likely to mention practical issues of a trial than were women previously treated for cancer, who were also more likely to mention emotional issues of clinical-trial participation

10

Private room or clinic

Those who refused participation less willing to experience short-term toxic effects for possible long-term gain and to give away treatmentdecision-making to physician

11

Clinic

Nothing particular to note

12

Hospital

Randomisation into non-cryotherapy group perceived as secondary (ie, less favourable) option

13

Hospital clinic

Patients prefer explanation of randomisation that is less explicit

14

Cancer centre

Middle-group socioeconomic respondents reported more willingness to participate in a trial than did those of lower socioeconomic status

15

Hospital oncology unit

Only 3 patients completed third and final interview; decrease in sample 16 size due to death and withdrawal from trial (reasons not given)

Telephone survey, mail survey, or cancer centre


17

Telephone surveys

Study participants knew little about trials and had no opportunity to participate; cultural factors thought to affect participation; and main concern was a "mistrust of white people" and being treated like "guinea pigs"

18

Hospital

African American women less likely to be aware of trials, know of 19 someone who had participated in a trial, or report that their oncologist had talked to them about participating compared with white women; this study was part of a larger study

University conference site


20

Not specified

Patients in rural areas less likely to participate in a trial than did those in urban areas; location of treatment centre and transportation more of a barrier for those in rural areas

21

Table 2: Characteristics of qualitative studies on barriers to participation in clinical trials—study populations


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Protocol-related barriers Trial Setting Dislike idea of randomisation General unease with research process Protocols too complex or stringent Assignment to placebo or no-treatment group Inconvenient to everyday life Potential side-effects Trials not appropriate for serious disease Trial or treatment does not offer best option Trial or treatment has no benefits Preference for other treatment Not informed or information given not adequate Other Patient-related barriers Concerns over costs or health insurance Transport or distance to trial site Lack of family support or increased anxiety Uncomfortable with experimentation Do not want to lose control of decision-making Feelings of uncertainty Quality of life might be reduced Fear or mistrust of research or researchers Other Physician-related barriers Negative effect on doctor–patient relationship Belief that doctor should make decisions Feeling coerced to join Physicians’ attitude towards trial



Combined studies

Ref 10

14

Ref 15

18

Ref 19

20

21

82

n 56

28

n 196

103

17

11

12

n 41

60

21

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13 11

16 7

17 100

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Table 3: Patient-identified barriers to participating in clinical trials from qualitative studies

Ten10–12,14–16,18–21 qualitative studies noted patient-related concerns towards participation in a clinical trial (table 3). Other patient-related barriers recorded were religious or cultural factors,15,20 and fear of discrimination.15,18,20,21 Eleven10–16,18–21 qualitative studies reported physicianrelated barriers to participation (table 3). To define the generalisability of the findings from qualitative studies, we pooled data for these barriers reported in quantitative papers (figure). We found significant heterogeneity in all pooled analyses (p0·05), which was not explained by our a-priori hypotheses that findings from randomised controlled trials would differ from those of experimental trials. All but one quantitative study reported protocol-related concerns (table 4). The figure shows the pooled proportions of participants who noted concern for barriers in the template, which were generated from a meta-analysis of the data. Other protocol-related barriers were recorded in these quantitative studies as: negative media attention,37 knowledge of the Tuskegee studies,31,33,37 and potential for cancer recurrence.28,31 All quantitative surveys reported patient-related barriers (table 4). Other patient-related barriers were religious or cultural factors,22 fear of discrimination on enrolment,28 fear that trial participation may be life144

threatening,31 patient wished to wait before trial entry,39 patient was too unwell or had deteriorating health,39 or patient did not want further blood tests.42 1223,25–27,29,30,32,33,36–39 quantitative studies reported physicianrelated barriers (table 4).

Discussion We have defined the nature and extent of barriers identified in qualitative and quantitative studies that are thought to hinder participation in clinical trials of cancer. To our knowledge, this is the first published systematic review to assess the concerns of patients with cancer regarding trial participation, and should be of interest to clinicians and, in particular, trialists. We identified several key themes that addressed specific patient-identified barriers to trial recruitment that were associated with the methods of the trial, interruptions to patient lifestyle, and concerns regarding interactions with their physicians. These findings should aid those who have a role in the planning, recruitment, and conduct of clinical research to make it more appealing for people living with cancer to enrol. The scientific and cancer communities have frequently raised concerns about the safety of candidate interventions and new regimens of currently available http://oncology.thelancet.com Vol 7 February 2006

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Ref 24

38

Ref 23

100

150

n 211

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n 887 Protocol-related barriers Dislike idea of randomisation General unease with research process Assignment to placebo or no-treatment group Inconvenient to everyday life Potential side-effects Trials not appropriate for serious disease Trial or treatment does not offer best option Trial or treatment has no benefits Preference for other treatment Not informed or information given not adequate Other Patient-related barriers Concerns over costs or health insurance Transport or distance to trial site Lack of family support or increased anxiety Uncomfortable with experimentation Do not want to lose control of decision-making Feelings of uncertainty Quality of life might be reduced Fear or mistrust of research or researchers Other Physician-related barriers Negative effect on doctor–patient relationship Belief that doctor should make decisions Feeling coerced to join Physicians’ attitude towards trial

●

25 60

26 545

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27 83 ●

323 ●

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29

30

265

204

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33 88

36 75

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154

34 216

35 328

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Ref 22

32

39

41

42

276

n 218

344

558

297

70

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31

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37

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28

Combined studies

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Table 4: Patient-identified barriers to participating in clinical trials from quantitative studies

drugs. Here, we have highlighted the uncertainty of those who live with cancer, emphasising the importance of addressing issues regarding the methods of a trial openly and thoroughly. Cancer research has been mixed in terms of its advances; however, many effective interventions would not be in use had it not been for the completion of successful clinical trials.43 Although the balance between societal benefits and individual patient benefits must be recognised, it seems appropriate to stress in particular the advances from clinical research with individual participants and the communities in which these studies are done.25,26 This contentious issue for ethicists and trialists is one that an institutional review board should be aware of because some critics have construed the potential societal benefit as coercion.44 In addition to the aim of easing participant anxieties, an approach that focuses on the individual patient might negate concerns related to mistrust of the scientific community and the research process in general.45 Study designs can be complex, and the terms used to characterise them (eg, blinding, randomised, and placebo) might confuse or dissuade otherwise eligible candidates from participation. The process of informed consent is an optimum time to define clearly such terms and provide candidates with the opportunity to clarify the meaning of the technical words used in clinical http://oncology.thelancet.com Vol 7 February 2006

research.46 The findings of this systematic review should be used in the development of informed-consent forms and detailed educational materials for patients. These materials should address clearly the issues of clinical research that are seen as most important by the potential participants. It is easy to comprehend why people who participate in clinical research might have misunderstandings regarding the intentions of those doing the research. Different ethnic backgrounds, languages, historical experiences, and levels of education contribute to mistrust of clinical researchers and the pharmaceutical industry.4,47 Sadly, history provides several examples as to why these concerns are justified.48,49 Successful conduct of clinical trials is therefore dependant on a concerted effort by those who do the research to communicate intentions clearly and to involve local investigators and the community in the conduct of research. We think that most of the concerns identified in our study can be alleviated with directed educational strategies. Many resources now exist for patients and their families who are in the process of deciding about entry into a clinical trial (eg, www.clinicaltrials.gov or www.ontariocancertrials.ca). Physicians, nurses, and clinical-research associates must be prepared to discuss thoroughly any concerns of prospective trial 145

Articles

Number of studies pooled

n*

Proportion, % (95% CI)

Dislike randomisation27,29,31,32,37

5

719

38 (35–42)

Dislike possibility of placebo24,29,30

3

1032

53 (50–56)

Inconvenience to everyday life26

1

545

35 (31–39)

Potential side-effects26,27,31,37,42

5

899

45 (37–55)

Trial not appropriate for diagnosis37

1

246

24 (19–29)

Trial treatments not best option26,37

2

791

44 (41–47)

Trial treatments offer no benefit23,32,35,37,42

5

1016

24 (14–41)

Preference for other treatment27,31,32,34,40

5

442

34 (20–58)

Not informed22,29,30,32

4

662

23 (21–26)

Concern over cost or health insurance22,40

2

255

17 (9–30)

Lack of family support27,39

2

587

10 (3–30)

Dislike being experimented on23,24,26,27,31,34,42

7

1851

19 (10–34)

Lose control over decision-making25,26,27,31,38

5

650

23 (20–26)

Too uncertain23,26,31,36

4

856

12 (10–14)

Quality of life might be reduced32,37

2

590

55 (51–59)

Negative effect of physician–patient relationship26

1

545

26 (22–29)

Physician should make decisions23,25,27,30

4

435

38 (33–42)

Feels coerced to join29,30

2

100

20 (10–29)

0

10

20

30

40

50

60

Proportion (%) of pooled responses

Figure: Proportion (%) of pooled responses identified as barriers to participation in clinical trials *Number eligible for meta-analysis.

participants—eg, those regarding loss of control over decision-making, a negative effect on the physician–patient relationship, and the idea that physicians should make the decisions can be addressed in patient populations that are open to clinical-trial participation but that have some valid concerns. For other patient populations that will choose adamantly not to participate in research, clinicians should be aware that some of these patients will perceive even the suggestion of research as coercion to participate. In our metaanalysis, we noted that 20% of 100 patients surveyed felt coerced to participate in a trial. Much work has been done on the issue of making enrolment onto clinical trials more appealing for participants and on ways in which enrolment can be increased through inclusive, non-coercive methods. For instance, Jenkins and colleagues50 have discussed extensively patient preferences regarding methods of randomisation, and have assessed strategies designed to enhance patient–physician communication.51 Importantly, studies that have addressed the effect of alleviating insurance concerns have identified both an inhibitory and a promotional effect on enrolment in clinical trials, suggesting that many of the other factors we have described are perhaps of greater importance.52,53 146

There are important strengths and limitations to our study. Because all studies were done in developed countries, we cannot determine to what extent our data apply to developing countries. Our study focused on barriers to entrance in clinical trials and did not address why many patients are not approached about enrolment onto a trial. Systematic reviewing of qualitative studies is a new area of research, and the methods used are continually changing.8,54–59 This study expands on our previous work,7,60 which assessed barriers to clinical-trial participation in other patient populations. We emphasise that the methods we used are specific, but not sensitive, for identification of barriers. We investigated heterogeneity between studies in our pooled analysis of study proportions. However, because of the small number of studies pooled, we cannot determine whether any heterogeneity identified is due to consistent differences across studies as a result of populations or diseases, or to the small number of studies. We acknowledge that the reporting of bias in the studies we included might have limited our ability to identify all barriers to participation in clinical trials of cancer.61 However, the presence of barriers in more than one qualitative study, consisting of mixed populations of patients, lends support to the conclusion that these http://oncology.thelancet.com Vol 7 February 2006

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barriers are broadly applicable. This finding is important because disadvantaged populations frequently have reduced opportunity to participate in clinical research.62 The use of surveys to quantify the importance of barriers identified in the qualitative setting further strengthens the generalisability of the specific barriers. Moreover, we attempted to contact all authors of quantitative studies, and were successful with ten of 17 authors whom we contacted for clarification. Future research could focus on populations that are difficult to enrol, such as minority ethnic groups and patients from low socioeconomic backgrounds. We included several such studies in our review; however, because many funding agencies need the inclusion of women, children, elderly people, and minority ethnic groups4 and because large trials need participation of such people for generalisability, we recognise the paucity of specific information on these important participants.63 The quantitative studies we assessed identified only a few of the barriers compared with qualitative studies, suggesting that key issues reported in qualitative surveys should be incorporated into subsequent quantitative studies. In particular, this systematic review has generated an inclusive and comprehensive list of factors that restrict patient involvement in clinical research. Future studies of this topic should address all the pertinent issues—a factor that will help generate data to inform the design and conduct of future clinical research in oncology in a way that is most conducive to patient participation. Contributors E J Mills, B Rachlis, P Wu, D Seely, and K Wilson did the search for qualitative and quantitative studies. E J Mills, B Rachlis, P Wu, D Seely, and L Griffith had a role in data analyses. All authors had a role in the study idea, in the writing of the report, and in approval for submission for peer-review. Conflict of interest We declare no conflicts of interest. Acknowledgments No funding was received for this study. We thank Pearl Raju for database searches. D Seely acknowledges career support from the Sick Kids Foundation (Hospital for Sick Children, Toronto, Ontario, Canada). References 1 Ries L, Eisner MP, Kosary CL, et al. SEER cancer statistics review 1975–2002. Bethesda: National Cancer Institute, 2004. 2 Ross M, Jeffords K, Gold J. Reasons for entry into and understanding HIV/AIDS clinical trials: a preliminary study. AIDS Care 1993; 6: 77–82. 3 Kaanoi M, Braun K, Gotay C, et al. Oncologists’ knowledge, attitudes and practices related to cancer treatment clinical trials. Hawaii Med J 2001; 61: 91–95. 4 Murthy V, Krumholz HM, Gross CP. Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA 2004; 291: 2720–26. 5 Townsley C, Selby R, Siu LL. Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials. J Clin Oncol 2005; 23: 3112–24. 6 CASP. Critical appraisal skills programme. Evidence-based healthcare. Workbook and CD-ROM. 10 questions for appraising qualitative research. http://www.updatesoftware.com/publications/casp/ (accessed Jan 12, 2006).


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