Publications by authors named "Nicole Simms"

5 Publications

  • Page 1 of 1

Industry, experts and the role of the 'invisible college' in the dissemination of non-invasive prenatal testing in the US.

Soc Sci Med 2021 Feb 23;270:113635. Epub 2020 Dec 23.

Institute of Health Policy, Management and Evaluation, University of Toronto, Health Sciences Building, 155 College Street, Suite 425, Toronto, ON, M5T 3M6, Canada. Electronic address:

Enthusiasm for so-called 'personalized' or 'precision' medicine has encouraged the growth of the molecular diagnostics industry and the proliferation of high-priced proprietary tests that can predict, diagnose or inform the treatment of diverse clinical conditions. Through a case study of non-invasive prenatal testing (NIPT), we explore how the mechanisms governing the development and dissemination of this novel prenatal screening test are most aptly understood as a 'regulatory regime.' We describe how private actors tied to the manufacturers of this test form a network of "experts" that contribute to the coordination of this regime by virtue of their efforts to navigate the governance of test adoption and also form spaces in which the standards governing test adoption are developed. We draw attention to private actors in this regime to demonstrate that they are a constitutive element of the public policy system governing biomedical innovation and adoption. Through this case study of NIPT we deepen our previous analysis of the role of consultants in navigating and shaping a regulatory regime (Holloway and Miller, 2020) and offer new insight about how scientists work with consultants to shape a regulatory regime that serves industry interests. Our work indicates that the private actors tied to the manufacturers of NIPT (experts employed by industry to court scientists and lobby payers, scientists collaborating with industry, key opinion leaders involved with clinical practice guidelines, lobbyists and consultants), constitute an 'invisible college' that navigates the governance of test adoption. The formations and negotiations over standards for NIPT identified in this paper comprise a new institutional norm: a polycentric regulatory regime permeated by commercial interests. The institutionalization of this regime has implications for accountability, transparency and test quality amidst a proliferation of new proprietary molecular tests.'
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http://dx.doi.org/10.1016/j.socscimed.2020.113635DOI Listing
February 2021

Easing anxiety in preparation for pediatric magnetic resonance imaging: a pilot study using animal-assisted therapy.

Pediatr Radiol 2019 07 27;49(8):1000-1009. Epub 2019 Apr 27.

Department of Diagnostic Imaging, The Hospital for Sick Children, 555 University Ave., Toronto, ON, M5G 1X8, Canada.

Background: Children undergoing magnetic resonance imaging (MRI) can experience negative emotions both before and during their scan, causing them to move and often necessitating the use of procedural sedation. Several strategies to improve patient compliance have been attempted.

Objective: This study was designed to evaluate the effectiveness of a non-pharmacological intervention to reduce anxiety in pediatric patients preparing for MRI using animal-assisted therapy.

Materials And Methods: An animal intervention pilot study was performed in patients who agreed in advance to interact with a dog. Patients and caregivers filled out questionnaires, including questions designed to capture changes in patient emotion before and after the intervention. MRI diagnostic quality was compared to age- and gender-matched control groups with and without general anesthesia.

Results: The intervention in 21 patients comparing pre- and post-scan surveys demonstrated a statistically significant improvement in patient anxiety levels (P<0.01). Diagnostic MRI scans were achieved in 19/21 (90%), with no significant difference in exam quality or times compared against control groups. The majority of caregivers and staff members agreed strongly that patients benefited from the therapy dog's presence.

Conclusion: The use of animal-assisted therapy in a pilot group in our MRI division resulted in a beneficial effect on patients' emotional status, easing anxiety in preparation for scheduled scans, without impacting MRI quality or duration. Further randomized studies will be needed to demonstrate its significance in reducing sedation rates in children undergoing MRI.
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http://dx.doi.org/10.1007/s00247-019-04407-3DOI Listing
July 2019

Signaling pathway screening platforms are an efficient approach to identify therapeutic targets in cancers that lack known driver mutations: a case report for a cancer of unknown primary origin.

NPJ Genom Med 2018 20;3:15. Epub 2018 Jun 20.

1Signalling Networks in Cancer Group, Cancer Research UK, Manchester Institute, University of Manchester, Manchester, M20 4BX UK.

Precision medicine aims to tailor cancer therapies to target specific tumor-promoting aberrations. For tumors that lack actionable drivers, which occurs frequently in the clinic, extensive molecular characterization and pre-clinical drug efficacy studies will be required. A cell line maintained at low passage and a patient- derived xenograft model (PDX) were generated using a fresh biopsy from a patient with a poorly-differentiated neuroendocrine tumor of unknown primary origin. Next-generation sequencing, high throughput signaling network analysis, and drug efficacy trials were then conducted to identify actionable targets for therapeutic intervention. No actionable mutations were identified after whole exome sequencing of the patient's DNA. However, whole genome sequencing revealed amplification of the 3q and 5p chromosomal arms, that include the and genes, respectively. We then conducted pathway analysis, which revealed activation of the AKT pathway. Based on this analysis, efficacy of PIK3CA and AKT inhibitors were evaluated in the tumor biopsy-derived cell culture and PDX, and response to the AKT inhibitor AZD5363 was observed both in vitro and in vivo indicating the patient would benefit from targeted therapies directed against the serine/threonine kinase AKT. In conclusion, our study demonstrates that high throughput signaling pathway analysis will significantly aid in identifying actionable alterations in rare tumors and guide patient stratification into early-phase clinical trials.
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http://dx.doi.org/10.1038/s41525-018-0055-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010465PMC
June 2018

The Combination of the PARP Inhibitor Olaparib and the WEE1 Inhibitor AZD1775 as a New Therapeutic Option for Small Cell Lung Cancer.

Clin Cancer Res 2018 10 25;24(20):5153-5164. Epub 2018 Jun 25.

Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, United Kingdom.

Introduced in 1987, platinum-based chemotherapy remains standard of care for small cell lung cancer (SCLC), a most aggressive, recalcitrant tumor. Prominent barriers to progress are paucity of tumor tissue to identify drug targets and patient-relevant models to interrogate novel therapies. Following our development of circulating tumor cell patient-derived explants (CDX) as models that faithfully mirror patient disease, here we exploit CDX to examine new therapeutic options for SCLC. We investigated the efficacy of the PARP inhibitor olaparib alone or in combination with the WEE1 kinase inhibitor AZD1775 in 10 phenotypically distinct SCLC CDX and/or These CDX represent chemosensitive and chemorefractory disease including the first reported paired CDX generated longitudinally before treatment and upon disease progression. There was a heterogeneous depth and duration of response to olaparib/AZD1775 that diminished when tested at disease progression. However, efficacy of this combination consistently exceeded that of cisplatin/etoposide, with cures in one CDX model. Genomic and protein analyses revealed defects in homologous recombination repair genes and oncogenes that induce replication stress (such as MYC family members), predisposed CDX to combined olaparib/AZD1775 sensitivity, although universal predictors of response were not noted. These preclinical data provide a strong rationale to trial this combination in the clinic informed by prevalent, readily accessed circulating tumor cell-based biomarkers. New therapies will be evaluated in SCLC patients after first-line chemotherapy, and our data suggest that the combination of olaparib/AZD1775 should be used as early as possible and before disease relapse. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-2805DOI Listing
October 2018

Vasculogenic mimicry in small cell lung cancer.

Nat Commun 2016 11 9;7:13322. Epub 2016 Nov 9.

Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, Manchester M20 4BX, UK.

Small cell lung cancer (SCLC) is characterized by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. We show that SCLC patients (37/38) have rare CTC subpopulations co-expressing vascular endothelial-cadherin (VE-cadherin) and cytokeratins consistent with vasculogenic mimicry (VM), a process whereby tumour cells form 'endothelial-like' vessels. Single-cell genomic analysis reveals characteristic SCLC genomic changes in both VE-cadherin-positive and -negative CTCs. Higher levels of VM are associated with worse overall survival in 41 limited-stage patients' biopsies (P<0.025). VM vessels are also observed in 9/10 CTC patient-derived explants (CDX), where molecular analysis of fractionated VE-cadherin-positive cells uncovered copy-number alterations and mutated TP53, confirming human tumour origin. VE-cadherin is required for VM in NCI-H446 SCLC xenografts, where VM decreases tumour latency and, despite increased cisplatin intra-tumour delivery, decreases cisplatin efficacy. The functional significance of VM in SCLC suggests VM regulation may provide new targets for therapeutic intervention.
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http://dx.doi.org/10.1038/ncomms13322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5105195PMC
November 2016