Reasons for and against participation in studies of medicinal therapies for women with breast cancer: a debate
BMC Medical Research Methodology volume 12, Article number: 25 (2012)
A special challenge for research studies of breast cancer among females is low patient participation rates. We compiled this systematic review to identify reasons why women with, or at high risk of, breast cancer do or do not participate in medicinal studies of breast cancer.
A systematic literature search in the databases Cochrane Library, EMBASE, Medline, Pascal Biomed, ACP Journal Club and CINAHL, as well as searches through reference lists of relevant texts, was performed.
Of 39 relevant full texts, ultimately, nine studies (1 qualitative, 8 quantitative) were included after applying the inclusion criteria. Despite a lack of data material, it was possible to identify various factors influencing women's willingness to participate in medicinal studies and group them into three categories: person-related, study-related, and physician-related.
Reasons for or against participation in studies of medicinal therapies by women with, or at high risk of, breast cancer are multi-dimensional, and should be considered when planning such studies to garner higher participation rates. For a more comprehensive picture of factors that affect participation, further studies in this field are recommended.
Recruitment of participants in breast cancer trials relative to the incidence of breast cancer patients is somewhat higher than in other cancer types, such as colorectal or lung cancer . However, the number of participants in breast cancer trials is still rather low. Estimates of participation of adult persons in cancer studies is about 1.5-11% of the total number of newly diagnosed or incidental cases [1, 2]. Low participation in studies can lead to under-representation, which, in turn, can result in an effect or a clinical effectiveness being shown as not significant  or in a failure to obtain theoretical data saturation . Low participation rates in a study may also induce bias, whereby those enrolled do not represent the target population very well. The reason why a planned sample size is not reached within the time frame can, among other things, depend on problems in recruiting participants . Research studies, grouped in reviews, have investigated possible barriers to cancer patients' participation in clinical studies [6–8]. Among these barriers are, for example, randomization, preferences for a certain therapy, degree of knowledge or additional effort in travel [6, 7].
In all of these studies however, patients with different cancer types were combined; for example, breast cancer, lung cancer and intestinal cancer, as well as various therapies.
To gain a better understanding of why especially female breast cancer patients frequently do not participate in clinical medicinal studies, a systematic review regarding this sensitive female patient group was conducted.
This review includes both qualitative and quantitative studies that discuss reasons and barriers or influencing factors for the participation of female breast cancer patients in medicinal studies. Clinical medicinal studies in this paper, are defined as studies with a variety of medical therapies, which may include, for example, chemotherapies, endocrine therapies and immune therapies within neo-adjuvant and adjuvant therapy .
In May 2011, a systematic literature search was carried out in the databases: Cochrane, EMBASE, Medline, Pascal Biomed, ACP Journal Club, and CINAHL. The following combination of MeSh-Terms and Keywords was chosen: #1: cancer OR tumo* OR oncolog* OR neoplasms; #2: willing* OR enrol* OR informed consent OR participat*; #3: clinical and trial*; #4: medica* or drug or pharma*; #5: breast; #6: #1 AND #2 AND #3 AND #4 AND #5.
Articles were limited to those published in the last 10 years in German or English. When uncertainties regarding whether the content of the studies was suitable for this review occurred while screening study abstracts (or when articles did not have abstracts), the respective full texts were procured for further evaluation. To find additional relevant literature, the reference lists of the full texts were searched for possible articles.
Inclusion criteria: studies that focused on participation or non-participation in clinical medicinal studies of adult women with breast cancer.
Exclusion criteria: studies that did not examine consent-competent female patients, did not focus on medications, investigated the effectiveness of medications, or did not refer to primary sources, study protocols and commentaries.
Full texts found in the literature research were evaluated regarding methodical or theoretical rigor by means of the applicable quality checklist for quantitative or qualitative studies of the Alberta Heritage Foundation for Medical Research ; texts with values < .75 by these criteria were not used.
The following data were extracted from the respective full texts: objective, study type/design, method, number and characteristics of the participants, definition of the term "study participation," setting, and results. These extracted data were compared and categorized with regard to factors influencing participation (for and against see Table 1 and 2) in clinical medicinal studies of women, regardless of which research area they originally came from. This categorization was performed according to Mills et al., 2006 .
After applying the selection criteria according to the title and abstract screening, 39 publications (of initially 3080 references) remained for further evaluation. Twelve publications were excluded as secondary literature, comments or protocols; 17 publications were excluded because their focus was not of interest (e.g., medicinal studies). One additional article was included from the reference lists. Two articles had to be excluded as they each had a quality score of < 0.75. Ultimately, 9 publications met the inclusion criteria and were subjected to further analysis and evaluation (see Figure 1).
Eight of these nine included studies were quantitative [11–18]; only one was qualitative . The summarized data extraction of the individual studies is found in Table 3. The quality assessments performed, including comments, are depicted in Tables 4 and 5, according to research areas. Four of the studies were conducted in the United States [12, 13, 17, 19], two in Canada [11, 14], and the rest in Europe; in Germany , France  and Italy . All of these articles have been published in English.
In the articles, a great variety of study designs were utilized as case-control , cohort  or randomized studies  (among others), where the design was not explicitly identified in most of them [11, 13–15, 18, 19]. The prevalent method used to elicit women's reasons for or against participation in studies with medicinal therapies were questionnaires [11–13, 15–18]. Most of the articles referred to investigations already performed, to identify the relevant reasons for consent or refusal to participate [12, 14, 15, 18, 19]. Three studies, though, used theoretical scenarios for the solicitation of reasons [11, 13, 16]. In one article, on the other hand, women were asked regarding their intent to participate in a currently active study .
The majority of the studies focused on chemotherapies [11, 12, 15–17, 19], whereas only one particularly referred to endocrine therapy , one to a new aromatase inhibitor, other endocrine therapy and chemotherapy , and another one generally to medicines .
Half of the studies addressed post-menopausal women, each with varying degrees of breast cancer risk [12, 15, 17–19], and half of the studies addressed women with invasive breast cancer [11, 13, 14, 16]. The studies mainly investigated women with an average age of 53 (range: 40-66 years) [11–18]. One study mainly included women in age groups 50-59, 60-69 and 70-79 years .
Discussion and conclusions
The various factors influencing participation in breast cancer medicinal research identified in the nine studies were placed by the authors into three categories: person-related, physician-related and study-related.
Regardless of whether study participants were younger or older, they frequently had high subjective perceptions of their risk of breast cancer [16, 18], although their objective risks, assessed according to Gail scores, in one of the two studies, were relatively low on average [17, 19, 20]. Another study also showed women who had participated in medication studies assessed their breast cancer risk subjectively much higher than women who had not participated, though both groups did not differ according to their Gail scores . This suggests that, in future studies, subjective perceptions of risk should be addressed. Also, in ovarian cancer investigations, potential subjects' higher personal risk perception and concern raised the probability of making use of screening [21, 22]. These results suggest that women's participation in such studies depends more on subjective risk than objective risk. Though subjective breast cancer risk in two studies in this review correlated with the women's willingness to participate [17, 19], in another medication study, women's participation was more likely when they were less personally concerned about breast cancer ; however, this last-mentioned study does not reveal whether relatives of the study participants had suffered from breast cancer or not, which could increase the subjects' concern, and thus interest, in participating in a medication study. One study showed women who had first and second degree relatives with breast cancer requested information about the medication study twice as often as women who did not have this diagnosis among their relatives (OR 2.35, 95% CI, 0.99-5.57).
Studies show a negative correlation between the concern regarding breast cancer and satisfaction with the physician's consultation . Nevertheless, satisfaction with physicians' consultation and communication processes (physician-related reason) was mentioned as reason for participation/non-participation in medication studies [16, 18], indicating that patient-clinician relationships play a decisive role in patients' willingness to participate in a study.
Identification of potential differences in consultations in the medication studies was not possible [11, 13, 16] because only one study reported the content of the conversations . Therefore, not all women in the studies might have been informed about the same things. To avoid this distortion in future studies, the use and documentation of conversation manuals in these consultations seems advisable.
The randomization procedure was mentioned in two studies as reason against participation [11, 19]; willingness for randomization was mentioned in one study as an influencing factor for participation . In cancer research, lack of understanding of the principle of randomization has been researched as barrier to subject participation [24, 25]. Another study showed that, among those who initially decided against participation in randomized studies, more than half ultimately consented to participation after they had received more detailed information regarding the randomization process . Though this connection was not identifiable from studies in this review, our results showed that randomization could influence participation in medication studies. Informing potential study subjects of the reasons for randomization could therefore promote their participation.
Fear of possible side-effects (a treatment-related reason) was also frequently mentioned as reason for non-participation [11, 15, 18, 19], suggesting that the probabilities for possible side-effects should be explained extensively during recruitment.
The review shows that the willingness to participate in the theoretical scenarios was considerably higher (58%; range: 25-75%) [11, 13, 16] than in studies that were actually, or yet to be, conducted (27%; range: 1.5-55%) [12, 14, 15, 17–19]. High willingness to participate in hypothetical scenarios is also seen in other studies [26–28]. Two studies collected their data retrospectively [12, 19], with the risk of recall bias in the results. Two other studies counteracted this bias by collecting would-be participants' relevant reasons immediately after consent or rejection of participating in their respective study [15, 18]. This procedure could also prevent such distortion in future studies.
A limitation of this review concerns its ten-year time frame. Although more full texts might have been included if our criteria allowed older investigations, the primary goal of this review was to identify current studies; we therefore restricted this study to the past decade.
The strengths of this review include its use of an extensive assessment scheme, allowing comprehensive quality evaluation of the respective articles, using consistent criteria. This scheme also could function as a kind of checklist, thus reducing the probability of forgetting any items in the assessment. Another strong point was that six databases were searched, allowing wide coverage of possible publications, as a result, of the articles gleaned from the references of all the full texts, only one was found that had not been part of the original database literature research. Inclusion of only high-quality studies is a further strength, as all studies had to show a high quality, of at least 75%, to be included in this review. Two studies did not meet this requirement and were therefore not included in the results [29, 30].
Physicians' viewpoints as to why women with breast cancer or breast cancer risk choose or decline to participate in medication studies is being researched, both with regard to general cancers  and breast cancer [24, 32], but not specifically with medication studies.
In sum, this review shows that the reasons for participation/non-participation in medication studies are multifactorial. Moreover, while factors affecting patient participation in medication studies are obviously useful to know in planning and realizing future investigations, few such insights are currently available, apparently due to the small number of relevant studies; further quantitative and qualitative research is needed.
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The authors declare that they have no competing interests.
All authors carried out the literature research, evaluated texts separately and discussed the results together. All authors drafted the manuscript and approved the final version.
Gero Luschin, Marion Habersack contributed equally to this work.
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Luschin, G., Habersack, M. & Gerlich, IA. Reasons for and against participation in studies of medicinal therapies for women with breast cancer: a debate. BMC Med Res Methodol 12, 25 (2012). https://doi.org/10.1186/1471-2288-12-25