Giulia KennedyPhD
VeracyteChapter 07 · Strand B · Achievement

Afirma

Veracyte's first product: a gene expression classifier that tells benign thyroid nodules from suspicious ones when cytology cannot. Launched January 2011, validated in the NEJM in 2012, 100,000 tests by 2018.

JAN 2011 – JAN 2018CHIEF SCIENTIFIC OFFICER, VERACYTEVERACYTE, INC. · SOUTH SAN FRANCISCO, CALIFORNIA

Overview

Afirma was the question Veracyte was built to answer. Fine-needle aspiration of a thyroid nodule leaves a sizeable minority of results indeterminate, and the usual response was diagnostic surgery that often removed a benign gland. Veracyte’s first commercial product, launched in January 2011, paired cytopathology with the Afirma Gene Expression Classifier, a 142-gene signature designed to identify the benign nodules among those cytology could not call.1

Contributions

Kennedy led research and development from the company’s first months and is credited by Veracyte with overseeing the development of the test.2 The development work, published in the Journal of Clinical Endocrinology & Metabolism in December 2010, measured mRNA expression across more than 247,186 transcripts in 315 thyroid nodules to train the classifier.3 The pivotal validation followed in the New England Journal of Medicine in 2012: a 19-month prospective, multicentre study at 49 clinical sites, enrolling 3,789 patients and 4,812 fine-needle aspirates. Kennedy is the paper’s second author.4

Impact

Announcing the NEJM publication on June 25, 2012, Veracyte said the study demonstrated the potential for the classifier to reduce unnecessary thyroid surgeries by more than half.5 By January 25, 2018 the company had performed more than 100,000 Afirma genomic tests and estimated that more than 40,000 patients had been spared having all or part of their thyroid removed unnecessarily.67

The original classifier was later succeeded by the RNA sequencing-based Afirma Genomic Sequencing Classifier, told in a later chapter.

From the record

Facts

  • Veracyte commercially launched the Afirma Thyroid FNA Analysis, incorporating the Afirma Gene Expression Classifier, in January 2011 as its first commercial product.16
  • The classifier was developed from 315 thyroid nodules using mRNA expression analysis of more than 247,186 transcripts, as described in the Journal of Clinical Endocrinology & Metabolism in December 2010.3
  • The prospective validation study published in the New England Journal of Medicine in 2012 ran for 19 months at 49 clinical sites, enrolling 3,789 patients and 4,812 fine-needle aspirates; Kennedy is second author.4
  • Veracyte announced the NEJM publication on June 25, 2012, saying the study showed the potential for the Afirma Gene Expression Classifier to reduce unnecessary thyroid surgeries by more than half.5
  • On January 25, 2018 Veracyte announced its 100,000th Afirma genomic test and estimated that more than 40,000 patients had avoided unnecessary thyroid surgery since 2011.67

Contributions

  • Led the research and development organisation that built and validated the Afirma Gene Expression Classifier, the first of three commercialized tests credited to her at Veracyte.2
  • Second author of the 2012 NEJM validation study of the classifier.4

Research

  • Thyroid nodule genomic classification

    APR 2008 – DEC 2022

    The programme that defined Veracyte, where Kennedy was Chief Scientific Officer from 2008 and Chief Medical Officer from 2018. The Afirma Gene Expression Classifier was developed from 315 nodules (JCEM, 2010), launched in January 2011 and validated prospectively in 3,789 patients (NEJM, 2012). The RNA sequencing-based Afirma GSC followed in 2017, validated in JAMA Surgery (2018) with at least one third more benign calls than the original test, and was extended with the Xpression Atlas of variants and fusions, Hürthle cell and medullary thyroid carcinoma classifiers. By January 2018 Veracyte had performed 100,000 Afirma tests.

  • Machine learning for clinical diagnostics

    DEC 2010 – PRESENT

    The method that links every classifier Kennedy has helped build since 2010: training algorithms on high-dimensional genomic data from clinical samples and validating them against histopathology. She presented on Veracyte's use of machine learning to translate genomic data into commercial diagnostic tests at the Precision Medicine World Conference in January 2018, and described the Afirma GSC's ensemble machine learning algorithms as deriving "from years of thoughtful scientific research, data analysis and statistical modeling". The same approach underlies the Envisia and Percepta classifiers and PinkDx's whole-transcriptome vaginal swab test.

Technologies
  • Afirma Gene Expression Classifier

Publications

Achievements

  1. JAN 2011milestone

    Commercial launch of Afirma

    Veracyte launched the Afirma Thyroid FNA Analysis, its first commercial product, combining cytopathology with the 142-gene Afirma Gene Expression Classifier for thyroid nodules that cytology leaves indeterminate.16

  2. 25 JAN 2018milestone

    100,000th Afirma genomic test

    Veracyte announced it had performed more than 100,000 Afirma genomic tests since the 2011 introduction and estimated that more than 40,000 patients had been spared unnecessary thyroid surgery.67

Impact

  • COMMERCIAL LAUNCH OF AFIRMA

    The first commercialized test developed under Kennedy as Chief Scientific Officer.

  • 100,000TH AFIRMA GENOMIC TEST

    Quantified clinical impact of the thyroid franchise Kennedy led scientifically.

Impact across the career