A Prospective Analysis Of Factors Affecting Successful Clinical Trial Enrollment And Randomization In The Context Of A Randomized Study Of Aggressive Local Therapy In Oligometastatic Non-Small Cell Lung Cancer

Purpose/Objective(s)Effective clinical trial enrollment can be difficult in protocol designs that contain one treatment arm that is perceived as being more “aggressive” than the other; however, there have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We therefore analyzed factors influencing enrollment over a 2-year time span in a trial-design that historically has had unfavorable accrual results: a randomized control trial (RCT) of immediate versus delayed aggressive “local therapy” (surgery or radiation) in patients with NSCLC and up to 3 sites of metastatic disease.Materials/MethodsFrom January 2013 through August 2014, patients with oligometastatic NSCLC were prospectively screened for RCT eligibility. All patients had an ECOG <3 and did not progress on standard induction chemotherapy (Step 1). The study then randomized patients to upfront local therapy to all sites of remaining disease versus further systemic therapy/observation (Step 2). Eligible candidates were approached about trial participation, and patient characteristics (age, gender, T/N stage, number/location of metastases) were recorded along with details surrounding trial presentation (appointment number, relation to Step 1). Fisher exact test and t-tests were performed to assess differences between enrolled and refusal patients.ResultsFrom January 2013 to August 2014, 82 eligible patients were approached about trial enrollment. The enrollment success rate (ESR) during this time span was 45% (n=47 patients enrolled), with an increase in ESR for each subsequent 6-month period (33%, 61%, 59%, 91%). The ESR in Step 1 versus Step 2 was 65% compared to 25% (P=.0049). Enrolled patients were more likely to be presented for consent at an earlier appointment (3 versus 5, P<.001), approached before/during Step 1 (91% vs 64%, P=.001), and have adrenal oligometastasis (28% vs 3%, P=.003). Interestingly, refusal patients were more likely to have been diagnosed at our institution (66% vs 38%, P=.02) and married patients were more likely to refuse the trial with borderline significance (86% vs 66%, P=.07). No other factors significantly affected ESR.ConclusionIn this study design that involved randomization to an upfront aggressive vs standard approach, ESR increased substantially with time. The factor most associated with successful enrollment was the timing of protocol presentation, suggesting that changes in trial design that lead to earlier protocol discussion may ultimately facilitate trial enrollment. We recommend consideration of this factor in the design of other RCTs with substantially different treatment regimens. Purpose/Objective(s)Effective clinical trial enrollment can be difficult in protocol designs that contain one treatment arm that is perceived as being more “aggressive” than the other; however, there have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We therefore analyzed factors influencing enrollment over a 2-year time span in a trial-design that historically has had unfavorable accrual results: a randomized control trial (RCT) of immediate versus delayed aggressive “local therapy” (surgery or radiation) in patients with NSCLC and up to 3 sites of metastatic disease. Effective clinical trial enrollment can be difficult in protocol designs that contain one treatment arm that is perceived as being more “aggressive” than the other; however, there have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We therefore analyzed factors influencing enrollment over a 2-year time span in a trial-design that historically has had unfavorable accrual results: a randomized control trial (RCT) of immediate versus delayed aggressive “local therapy” (surgery or radiation) in patients with NSCLC and up to 3 sites of metastatic disease. Materials/MethodsFrom January 2013 through August 2014, patients with oligometastatic NSCLC were prospectively screened for RCT eligibility. All patients had an ECOG <3 and did not progress on standard induction chemotherapy (Step 1). The study then randomized patients to upfront local therapy to all sites of remaining disease versus further systemic therapy/observation (Step 2). Eligible candidates were approached about trial participation, and patient characteristics (age, gender, T/N stage, number/location of metastases) were recorded along with details surrounding trial presentation (appointment number, relation to Step 1). Fisher exact test and t-tests were performed to assess differences between enrolled and refusal patients. From January 2013 through August 2014, patients with oligometastatic NSCLC were prospectively screened for RCT eligibility. All patients had an ECOG <3 and did not progress on standard induction chemotherapy (Step 1). The study then randomized patients to upfront local therapy to all sites of remaining disease versus further systemic therapy/observation (Step 2). Eligible candidates were approached about trial participation, and patient characteristics (age, gender, T/N stage, number/location of metastases) were recorded along with details surrounding trial presentation (appointment number, relation to Step 1). Fisher exact test and t-tests were performed to assess differences between enrolled and refusal patients. ResultsFrom January 2013 to August 2014, 82 eligible patients were approached about trial enrollment. The enrollment success rate (ESR) during this time span was 45% (n=47 patients enrolled), with an increase in ESR for each subsequent 6-month period (33%, 61%, 59%, 91%). The ESR in Step 1 versus Step 2 was 65% compared to 25% (P=.0049). Enrolled patients were more likely to be presented for consent at an earlier appointment (3 versus 5, P<.001), approached before/during Step 1 (91% vs 64%, P=.001), and have adrenal oligometastasis (28% vs 3%, P=.003). Interestingly, refusal patients were more likely to have been diagnosed at our institution (66% vs 38%, P=.02) and married patients were more likely to refuse the trial with borderline significance (86% vs 66%, P=.07). No other factors significantly affected ESR. From January 2013 to August 2014, 82 eligible patients were approached about trial enrollment. The enrollment success rate (ESR) during this time span was 45% (n=47 patients enrolled), with an increase in ESR for each subsequent 6-month period (33%, 61%, 59%, 91%). The ESR in Step 1 versus Step 2 was 65% compared to 25% (P=.0049). Enrolled patients were more likely to be presented for consent at an earlier appointment (3 versus 5, P<.001), approached before/during Step 1 (91% vs 64%, P=.001), and have adrenal oligometastasis (28% vs 3%, P=.003). Interestingly, refusal patients were more likely to have been diagnosed at our institution (66% vs 38%, P=.02) and married patients were more likely to refuse the trial with borderline significance (86% vs 66%, P=.07). No other factors significantly affected ESR. ConclusionIn this study design that involved randomization to an upfront aggressive vs standard approach, ESR increased substantially with time. The factor most associated with successful enrollment was the timing of protocol presentation, suggesting that changes in trial design that lead to earlier protocol discussion may ultimately facilitate trial enrollment. We recommend consideration of this factor in the design of other RCTs with substantially different treatment regimens. In this study design that involved randomization to an upfront aggressive vs standard approach, ESR increased substantially with time. The factor most associated with successful enrollment was the timing of protocol presentation, suggesting that changes in trial design that lead to earlier protocol discussion may ultimately facilitate trial enrollment. We recommend consideration of this factor in the design of other RCTs with substantially different treatment regimens.