Numerous characteristics of a pharmacogenetic study contribute to its success, and in this study, we identified several potential elements of successful recruitment in pediatric pharmacogenetics trials. Twelve items varied among the studies ().
Six characteristics were considered beneficial based on having at least a 25% difference in consent rates () and association with increased proportion of patients consenting () were (1) experienced study coordinator, (2) standardized clinical care, (3) ongoing team/patient relationship, (4 - tie) research team is the clinical team, (4 - tie) no/few clinical treatment alternatives, and (6) severe/life-threatening outcome measure.
Clinical environments with research integration appear to promote positive perceptions and attitudes among clinicians, patients, and families, and encourage participation and dedication to the study. Yet even in these motivated settings, with a large number of potentially eligible patients, clinician investigators with time limitations and clinical responsibilities may not be able to lead these efforts alone. In fact, the factor most closely tied to recruitment success in this study was the presence of an experienced study coordinator, which endorses the crucial involvement of clinical research coordinators.42,43
Sufficient means to identify and approach patients and families is critical, highlighting the importance of an ongoing relationship between researchers and patients/families and stressing the importance of trained personnel to coordinate recruitment. When the research team is also the clinical team who cares for the patient and interacts with the family, the established relationship and trust appeared to enhance the family's willingness be an important part of the clinician's research. Likewise, when the outcome is potentially severe or life-threatening, and families feel a study may help their child, or their participation in a study may help improve therapy for other patients and families battling the condition in the future, there is a higher rate of participation.
Three items appeared to contribute to successful recruitment but did not reach this study's pre-determined significance of 25% difference: access to or availability of department / divisional resources, observational (rather than interventional) study design, and time to reach outcome of fewer than 7 days (versus 7 or more days). Although investigators presumed a shorter time to reach and measure the outcome of interest may increase recruitment due to a more timely availability of treatment outcome measures for patients and families, this item was not associated with a meaningful increase in consent rate. Although the observational study design centered on allowing clinical care to proceed as usual with minimal added burden, this factor did not substantially contribute to successful recruitment. Each factor was associated with a positive impact (8.0%–10.9%), thus was not unfavorable, but none of these items alone contributed to a meaningful increase in recruitment.
Three items were not advantageous, but were not detrimental () to recruitment in pediatric pharmacogenetic studies: clinician champion with protected time for research, mentors with clinical research experience, and lead/site investigator experienced in clinical research. While these features may influence other pre-study elements, they did not result in meaningful increases in recruitment in the seven trials evaluated as part of the present study.
One limitation to this study is exclusion of factors common to all studies (biostatistician, objective outcome measures, external funding of clinician champion) from analyses, some of which, such as biostatistician involvement from the planning stages, have been demonstrated to be beneficial for trial feasibility and securing funding.42
Consequently, the benefit (or detriment) to having these characteristics on recruitment rates was not determined and cannot be presumed. Additionally, the survey was not able to investigate all factors which may influence recruitment, including lack of examination of socioeconomic status or subjects' and families prior involvement in research, as these data were not consistently collected across studies.
Another potential limitation is that there was not weighting of means; each study was equally weighted, regardless of the number of subjects approached. The study, not the number of subjects, was the experimental unit, hence the rationale for this approach. An alternative to our method of weighting studies equally, a weighting of means by the number of subjects, could be performed and may be more appropriate when investigators want to capture important factors by subjects rather than studies.
Overall, there were small numbers of trials examined, investigators surveyed, and subjects recruited in pharmacogenetic studies. The single study with poor recruitment may owe enrollment difficulty more to study design, specifically restrictive exclusion criteria, than to the factors assessed in the survey. When we remove this study from the analysis, a positive correlation (r=0.45) is still observed between a study's total score on the investigator-devised scoring tool and the proportion of patients recruited. However, given only a sample size of 6, this moderate correlation coefficient is not statistically significant with a p-value of 0.37. This suggests an effect of additional study design features on recruitment.
A weakness of this study is the inability of the survey to address the differential impact of race and ethnicity on pharmacogenetic study recruitment. Only one study recruited regionally and one nationally, the remainder recruited from the Cincinnati, Ohio area (a 13 county region in Ohio, Kentucky, and Indiana). In this region 59.7% of people are Caucasian, 19.1% black, 16.9% other, 2% multiracial, 1.3% Hispanic, 0.8% Asian/Pacific Islander, and 0.1% American Indian/Alaska native. If there are racial or ethnic effects on recruitment, this survey would not have been able to detect it.