We identified an important factor associated with increased probability of participants dropping out of a clinical trial: a delay in initiation and increased duration of screening is associated with decreased willingness to participate after enrollment in clinical trials. In this trial the delay in contacting the patient after consent, was determined primarily by the patient and was not due to delays on part of the research team, since patients were asked to state a day and time of their choice for research team to call for symptom screening. Thus, patients who defer participation for a longer period are more likely to drop before completion. This may be a passive resistance to participation by those who find it difficult to refuse outright. It is possible that this effect may be due to the fact that patients for whom it took longer to make the first screening call were also more severely ill and felt a need to delay their screening and eventually dropped out. However this is unlikely since a comparison of the means of total symptom severity score and interference with enjoyment of life scores between patients who were above and below the mean contact time (7 days) showed no difference (Severity: above mean 51.42, below mean 51.03, p = 0.87 and Interference: above mean 3.95, below mean 3.91, p = 0.86). This shows that both groups of patients were similar in terms of disease severity and perceived impact of their disease on their lives suggesting that these are not explanations for differences in attrition.
Another time span associated with higher attrition was the duration of screening. Longer time taken to complete the screening process increased the probability of attrition of all patients, but for minority patients elapsed time had a greater impact than for white patients (). This moderating effect of delay on race suggests a greater susceptibility of minorities to drop out when recruitment or screening process takes longer to complete. Historically, minority patients have been less likely to participate in clinical trials [18
], therefore the concerns about the external validity of the findings from the trials led to a 1993 National Institutes of Health’s (NIH) revitalization act (Public law 103-43), which resulted in increased recruitment of women and minority patients in research, particularly phase III clinical trials [19
]. However increased recruitment does not guarantee increased retention and thus patients who may have been initially reluctant to participate but consented because of focused efforts by study teams to recruit them, dropped out in early stages of the study. Our data support this explanation, as 70% of the patients completed screening within two days after initiation of screening. However when these numbers were examined separately by race, only 57% of the minorities as compared to 73% of white patients completed screening within two days. The delays experienced in completion of screening were primarily due to inability of study personnel to contact patients rather than because patient failed to score at least one symptom above threshold. The average duration of screening was also significantly longer for minority patients (5.5 vs. 3.1, p < 0.01). Therefore the minority patients were harder to contact during screening, and with the fact that were more likely to drop out, reflects a ‘mechanism’ by which minority patient quit clinical trials before completion.
It can be argued that patients who completed screening within a shorter duration were more symptomatic, whereas those who took longer to complete screening may have been less symptomatic and may have had less interest in the trial. This is however, seems an unlikely explanation for higher attrition among patients who took longer to complete screening because the time taken to complete screening was mainly determined by time taken to reach the patients, i.e. when calls to patients went unanswered, and not because the patient was reached but had not crossed the threshold. Therefore it is probably not true that those who completed screening faster were more symptomatic. Additionally, even if this were true it would not explain differential attrition by race for screening duration in days.
Ethnically, very few patients in our sample were Hispanic and almost all white patients (98.1%) were non-Hispanic. Differences in attrition were therefore found by race only.
The race and educational attainment of patients played a role in patient attrition in both phases of the study (from consent to screening initiation and from screening to the intake interview). Therefore minorities and the less educated patients continued to be more likely to drop-out throughout the study, and the effect of race and education on attrition persists across the trajectory from consent to beginning the intake interview. Since most of the patients who were found eligible to continue in the study had their eligibility established within 3 days of the first screening call, some patients who didn’t intend to continue with the trial didn’t have enough time to make their intentions known. Therefore, they dropped out at the next phase of our observation. The role of education and race in attrition as found in our study is consistent with findings of other researchers [14
Patients reporting a higher impact of their symptoms on their enjoyment of life were found to be more likely to drop out. The symptom interference with enjoyment of life was highly correlated with the total severity reported by patients calculated as the sum of severity over all symptoms (ρ = 0.66, p-value < 0.01), therefore the addition of the severity variable to the model did not effect the significance of enjoyment of life variable indicating that interference with enjoyment of life had an independent effect on attrition that was above and beyond any influence of symptom severity on attrition. The enjoyment of life may be thought of as a proxy variable for depression or at least a pre-depression state [20
]. The significant effect of interference with the enjoyment of life on attrition is therefore not surprising as depression is one of the most consistently reported factors associated with attrition in contemporary literature [21
One limitation of this research was that we were unable to establish if the delay in attempting to conduct the baseline interview after completion of screening had an effect on attrition (just as the delay in initiating screening contact had). Since attrition at this step was defined as failure to complete baseline interview the time from completion of screening to baseline interview could not be determined for the drop-outs.
The very nature of the trial and the intervention can be a strong determinant of a trial participant’s decision to continue or drop out.. Our trials are no exception and some of the participants may certainly have perceived the intervention more beneficial to them than others, influencing their decision to stay in or drop out of the study. However, the research reported here applies to the period of the study before any of the participants were delivered any intervention; therefore we do not expect the trials context to be factor influencing participants’ likelihood of dropping out at this early stage in the trial.