{Reference Type}: Journal Article
{Title}: Clinical exome sequencing vs. usual care for hereditary colorectal cancer diagnosis: A pilot comparative effectiveness study.
{Author}: Niu X;Amendola LM;Hart R;Bennette CS;Heagerty P;Horike-Pyne M;Trinidad SB;Rosenthal EA;Comstock B;Nefcy C;Hisama FM;Bennett RL;Grady WM;Gallego CJ;Tarczy-Hornoch P;Fullerton SM;Burke W;Regier DA;Dorschner MO;Shirts BH;Robertson PD;Nickerson DA;Patrick DL;Jarvik GP;Veenstra DL;
{Journal}: Contemp Clin Trials
{Volume}: 84
{Issue}: 0
{Year}: 09 2019
{Factor}: 2.261
{DOI}: 10.1016/j.cct.2019.105820
{Abstract}: Clinical exome sequencing (CES) provides the advantage of assessing genetic variation across the human exome compared to a traditional stepwise diagnostic approach or multi-gene panels. Comparative effectiveness research methods offer an approach to better understand the patient-centered and economic outcomes of CES.<BR>To evaluate CES compared to usual care (UC) in the diagnostic work-up of inherited colorectal cancer/polyposis (CRCP) in a randomized controlled trial (RCT).<BR>The primary outcome was clinical sensitivity for the diagnosis of inherited CRCP; secondary outcomes included psychosocial outcomes, family communication, and healthcare resource utilization. Participants were surveyed 2 and 4 weeks after results return and at 3-month intervals up to 1 year.<BR>Evolving outcome measures and standard of care presented critical challenges. The majority of participants in the UC arm received multi-gene panels [94.73%]. Rates of genetic findings supporting the diagnosis of hereditary CRCP were 7.5% [7/93] vs. 5.4% [5/93] in the CES and UC arms, respectively (P = 0.28). Differences in privacy concerns after receiving CRCP results were identified (0.88 in UC vs 0.38 in CES, P = 0.05); however, healthcare resource utilization, family communication and psychosocial outcomes were similar between the two arms. More participants with positive results (17.7%) intended to change their life insurance 1  month after the first return visit compared to participants returned a variant of uncertain significance (9.1%) or negative result (4.8%) (P = 0.09).<BR>Our results suggest that CES provides similar clinical benefits to multi-gene panels in the diagnosis of hereditary CRCP.