Demonstrating clinical utility for a novel nasal swab genomic classifier for lung nodules: addressing the clinical trial learning curve

SESSION TITLE: Chest Infections and Disorders of the Pleura Abstract PostersSESSION TYPE: Original Investigation PostersPRESENTED ON: 10/18/2022 01:30 pm - 02:30 pmPURPOSE: Percepta Nasal Swab is a novel genomic classifier that uses expression data from a brushing of nasal epithelium to assess the risk of malignancy in patients with a pulmonary nodule (PN) and history of tobacco exposure. We are now initiating a randomized controlled trial (RCT) to establish clinical utility (CU). Little is known about the impact of the learning curve on investigators in clinical trials. Investigators at the end of a trial will have more experience with aspects of the protocol than they do at the start; data from patients enrolled early may differ from those enrolled later. In analytical trials for laboratory testing a ‘Familiarization Phase’ is common, but this is not the case in clinical trials. We describe a 2-phase study protocol with a Familiarization Phase designed to mitigate learning curve effects in the CU study and present preliminary data from the study to date.METHOD: Percepta Nasal Swab is used for risk stratification of PN (low, moderate, high), utilizing RNA whole-transcriptome expression data from nasal epithelial cells collected with a soft cytology brush. Acquisition of cells to yield sufficient RNA requires experience, and the result must be used to inform decision-making. Prior to initiation of the CU RCT we enrolled sites in an IRB-approved Familiarization Phase. Patients ages 29-85 with a new PN <=30mm and a history of >100 cigarettes lifetime were eligible. Sites were required to have 9 of 10 sequential swabs meet minimum RNA adequacy and demonstrate use of the results in patient management to progress to the RCT. Data was collected on clinical factors, pre-test assessed ROM, and management plan before and after a test result.RESULTS: The study is ongoing. 7 sites have enrolled a total of 46 patients (range 1 to 13) with 40/46 (87%) meeting eligibility criteria. Adequate RNA was obtained from 45/46 (98%) of swabs in all enrolled subjects. Of the eligible subjects 40% were male. Average nodule size was 7.9 mm. 27% were spiculated. 16 (40%) nodules had a low-risk result; 12 (30%) were moderate- risk; 9 (23%) were high-risk; 3 (8%) are in process. In 88% of cases where a classifier result was obtained, physicians incorporated the test into their management plan. Rates of ineligible or unevaluable patients dropped from 16% at the start of the study to 9% at the time of this analysis. In the sites where familiarization was completed, the average data entry error rate was reduced from 8.6% at first enrollment to 1.8% at last enrollment.CONCLUSIONS: A Familiarization Phase allows investigators to acquire experience with study processes prior to initiation of a CU study. Preliminary data suggests that over the course of familiarization, study administrators were able to improve issues with enrollment of unevaluable patients and data entry errors.CLINICAL IMPLICATIONS: A Familiarization Phase may mitigate potential learning curve effects on clinical trial outcomes.DISCLOSURES: No relevant relationships by Michael BernsteinEmployee relationship with Veracyte Please note: 2/1/2021-present by William Bulman, value=SalaryEmployee relationship with Veracyte, Inc. Please note: >$100000 by Janna Chamberlin, value=SalaryEmployee relationship with Veracyte, Inc. Please note: $20001 - $100000 by Janna Chamberlin, value=Stock holderEmployee relationship with Veracyte Please note: >$100000 by Jing Huang, value=SalaryEmployee relationship with Veracyte Please note: >$100000 by Marla Johnson, value=SalaryEmployee relationship with Veracyte, Inc. Please note: 2008-present by Giulia Kennedy, value=SalaryEmployee relationship with Veracyte Please note: 4.5 years Added 03/31/2022 by Lori Lofaro, value=SalaryRemoved 06/08/2022 by Lori LofaroEmployee relationship with Veracyte Please note: 5 years Added 06/08/2022 by Lori Lofaro, value=SalaryNo relevant relationships by Farah Madhani-LovelyEmployee relationship with Veracyte, Inc. Please note: 07/2018 - Present Added 03/31/2022 by Eric Morrie, value=Salary SESSION TITLE: Chest Infections and Disorders of the Pleura Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: Percepta Nasal Swab is a novel genomic classifier that uses expression data from a brushing of nasal epithelium to assess the risk of malignancy in patients with a pulmonary nodule (PN) and history of tobacco exposure. We are now initiating a randomized controlled trial (RCT) to establish clinical utility (CU). Little is known about the impact of the learning curve on investigators in clinical trials. Investigators at the end of a trial will have more experience with aspects of the protocol than they do at the start; data from patients enrolled early may differ from those enrolled later. In analytical trials for laboratory testing a ‘Familiarization Phase’ is common, but this is not the case in clinical trials. We describe a 2-phase study protocol with a Familiarization Phase designed to mitigate learning curve effects in the CU study and present preliminary data from the study to date. METHOD: Percepta Nasal Swab is used for risk stratification of PN (low, moderate, high), utilizing RNA whole-transcriptome expression data from nasal epithelial cells collected with a soft cytology brush. Acquisition of cells to yield sufficient RNA requires experience, and the result must be used to inform decision-making. Prior to initiation of the CU RCT we enrolled sites in an IRB-approved Familiarization Phase. Patients ages 29-85 with a new PN <=30mm and a history of >100 cigarettes lifetime were eligible. Sites were required to have 9 of 10 sequential swabs meet minimum RNA adequacy and demonstrate use of the results in patient management to progress to the RCT. Data was collected on clinical factors, pre-test assessed ROM, and management plan before and after a test result. RESULTS: The study is ongoing. 7 sites have enrolled a total of 46 patients (range 1 to 13) with 40/46 (87%) meeting eligibility criteria. Adequate RNA was obtained from 45/46 (98%) of swabs in all enrolled subjects. Of the eligible subjects 40% were male. Average nodule size was 7.9 mm. 27% were spiculated. 16 (40%) nodules had a low-risk result; 12 (30%) were moderate- risk; 9 (23%) were high-risk; 3 (8%) are in process. In 88% of cases where a classifier result was obtained, physicians incorporated the test into their management plan. Rates of ineligible or unevaluable patients dropped from 16% at the start of the study to 9% at the time of this analysis. In the sites where familiarization was completed, the average data entry error rate was reduced from 8.6% at first enrollment to 1.8% at last enrollment. CONCLUSIONS: A Familiarization Phase allows investigators to acquire experience with study processes prior to initiation of a CU study. Preliminary data suggests that over the course of familiarization, study administrators were able to improve issues with enrollment of unevaluable patients and data entry errors. CLINICAL IMPLICATIONS: A Familiarization Phase may mitigate potential learning curve effects on clinical trial outcomes. DISCLOSURES: No relevant relationships by Michael Bernstein Employee relationship with Veracyte Please note: 2/1/2021-present by William Bulman, value=Salary Employee relationship with Veracyte, Inc. Please note: >$100000 by Janna Chamberlin, value=Salary Employee relationship with Veracyte, Inc. Please note: $20001 - $100000 by Janna Chamberlin, value=Stock holder Employee relationship with Veracyte Please note: >$100000 by Jing Huang, value=Salary Employee relationship with Veracyte Please note: >$100000 by Marla Johnson, value=Salary Employee relationship with Veracyte, Inc. Please note: 2008-present by Giulia Kennedy, value=Salary Employee relationship with Veracyte Please note: 4.5 years Added 03/31/2022 by Lori Lofaro, value=Salary Removed 06/08/2022 by Lori Lofaro Employee relationship with Veracyte Please note: 5 years Added 06/08/2022 by Lori Lofaro, value=Salary No relevant relationships by Farah Madhani-Lovely Employee relationship with Veracyte, Inc. Please note: 07/2018 - Present Added 03/31/2022 by Eric Morrie, value=Salary