Summary in Thirty Seconds
Without measurement, certain vital elements are never intentionally changed. In cancer research, one such unmeasured yet key metric is awareness of new and emerging biomarkers.
Awareness of biomarkers is vital because oncology healthcare providers will neither test for nor treat a specific genetic variant driving a patient’s particular cancer if they don’t know about it.
Celerity’s awareness algorithm is operationalized as trending, which is how much a specific element or issue is in the awareness of HCPs at a given time, and awareness, which is how awareness builds over time, rather than at a given time.
Using this trending and awareness algorithm allows pharmaceutical developers and healthcare providers the opportunity to measure real-world and digital awareness of emerging elements and associated clinical trials in oncology and genetic variants across specific professions and populations.
This allows the chance to develop compliant approaches to build awareness and track how successful these targeted efforts are.
The Importance of Biomarker Awareness
“You can’t improve what you don’t measure” is a quote commonly attributed to Peter Drucker, a founder of management theory. Yet many key factors go unmeasured because no one has devised a method to quantify them. And, without measurement, certain vital elements are never intentionally changed. In cancer research, one such unmeasured yet key metric is awareness of new and emerging biomarkers. Awareness of biomarkers is vital because oncology healthcare providers will neither test for nor treat a specific genetic variant driving a patient’s particular cancer if they don’t know about it. But how do we know if what we're doing to improve awareness of a biomarker is working effectively if it’s not being measured? And without awareness of such biomarkers, enrollment will lag in clinical trials centered around biomarkers.
Celerity has been working on compliant awareness strategies since 2017 for rare disease clinical trials. This work originated from the team’s experience with Neurotrophic Tyrosine Receptor Kinase (NTRK) fusions. Arising from this work is an AI-based approach to monitoring awareness among healthcare providers (HCPs) for a given emerging molecular diagnostic or clinical trial. This awareness algorithm includes a combination of real-world and digital behavior patterns, evaluated based on profession, and built from years of data in a given disease area. Once this database is built and carefully curated, we can look at trending and awareness differences and change for a given biomarker, clinical trial, or drug over time, and ask some intriguing questions. Do lung oncologists become aware of new biomarkers more quickly than other oncologist peers? How significant is the awareness advantage for the first clinical trial program for a given new biomarker over followers? How much lag is there in awareness between oncologists and pathologists, if any? What awareness differences are there between major cancer center oncologists who typically are engaged in new biomarker-driven trials compared to community/hospital oncologists who see the vast majority of cancer patients and provide first-line cancer care?
Trending and Awareness
As we began evaluating data to develop this metric, it was clear that awareness could be operationalized in at least two ways. One is trending, which is how much a specific element or issue is in the awareness of HCPs at a given time. The second is cumulative awareness, which is how awareness builds over time, rather than at a given time. Once aware of something, a person doesn’t become “unaware” of it, so awareness always shows a positive progression, whereas trending will rise and fall.
NTRK Example
NTRK is a compelling example of the power of our awareness analysis. NTRK was first identified as an oncogene in 1982;[1] however, it took almost three decades for researchers to understand the mechanisms by which NTRK fusions drove cancer,[2] leading to the development and testing of NTRK-fusion-treating tyrosine kinase inhibitors (TKIs) in the mid-2010s.[3],[4] At the end of that decade, two TKIs (larotrectinib[5] [Loxo] and entrectinib[6] [Ignyta]) were given FDA approval for the treatment of NTRK fusion-positive cancers. As a team that has been very active in the NTRK space from the early days of Ignyta and Loxo and more recently with large pharmaceutical companies, the Celerity team was curious to look at trending and awareness patterns over time across different types of healthcare providers (HCPs).
NTRK Trending
We hypothesized that cancer researchers would show trending first, followed by lung oncologists, then all oncologists, then pathologists. The following graph summarizes our trending analysis:
As can be seen from this graph, trending spiked significantly after 2019, driven by remarkably strong clinical trial results and FDA approval for drugs from both Loxo[7] and Ignyta.[8] This trending was seen first in molecular pathologists, cancer researchers, and oncologists, followed by general pathologists and lung pathologists later. The later trending rise in pathologists vs. molecular pathologists may be because the molecular pathologists shared the NTRK clinical trial results with their various pathology colleagues. Moving further in time, trending levels surprisingly declined for cancer researchers and pathologists and stayed relatively flat for molecular pathologists after these data releases instead of staying high, perhaps due to the realization of how rare these TRK fusions are in patients (overall NTRK fusion-positive tumor prevalence is approximately 0.30% in adults across 45 cancers).[9]
NTRK Awareness
NTRK awareness analysis shows that all HCPs became increasingly aware of NTRK fusions over time, with molecular pathologists, cancer researchers, and oncologists first showing the strongest awareness rises at the time of the initial clinical trial results, followed by steady increases in lung oncologists and pathologists, possibly driven by FDA approval for the two TKIs (larotrectinib and entrectinib) in 2018-2019.
TKI Trending
The question of why trending and awareness for NTRK rose notably after 2019 led to an analysis of trending patterns for larotrectinib, entrectinib, and repotrectinib resulting in the following results:
Trending had a spike in 2019 after these two TKIs obtained FDA approval, and trending has grown notably in 2021 and 2022, most likely because of increased awareness of the NTRK fusions and shared success rates of these two drugs for cancers driven by these fusions. Additionally, until successes were seen in clinical trials (pre-2018), neither compound generated much attention. Another important point in this trending analysis is that the first successes in a particular molecular treatment have the trending and awareness advantage, and they maintain this over time. While repotrectinib shows a trending gain in 2022, it is not nearly as large of a spike as seen for the first two TKIs.
TKI Awareness The TKI awareness builds over time; however, given the fact that repotrectinib was introduced much later than the first two TKIs, it lags behind them in awareness. Furthermore, larotrectinib was the first to obtain FDA approval; thus, it gains an awareness advantage over entrectinib and maintains that edge over time. These findings emphasize the point that the earlier an element is successfully introduced, the better it gains and maintains an awareness edge over its competition.
Building Trending and Awareness
Nothing can be changed that isn’t first measured. Using Celerity’s trending and awareness algorithm approach allows pharmaceutical developers and healthcare providers the opportunity to measure the real-world and digital awareness of emerging elements and associated clinical trials in oncology and genetic variants across specific professions and populations. This allows the chance to develop compliant approaches to build awareness and track how successful these targeted efforts are.
One of the first things Celerity finds effective in working with biotech or pharma partners is to initially analyze existing awareness patterns for a given class of clinical trial programs or biomarker strategies. Only after careful analysis do we design push/pull awareness strategies tailored to the situation, which might include digital media, webinars, SEO, or field-based “boots on the ground” approaches, particularly in international settings.
If you don’t measure it, you can’t impact it.
[1] Nature. 1982; 300:539–542 [2] Cancer Discovery. 2015; 5:25–34 [3] Journal of Medicinal Chemistry. 2016; 59:3392–3408 [4] Cancer Discovery. 2015; 5:1049–1057 [5] Vitrakvi (larotrectinib) FDA Approval History - Drugs.com [6] Rozlytrek (entrectinib) FDA Approval History - Drugs.com [7] N. Engl. J. Med. 2018; 378(8):731–739 [8] Lancet Oncol. 2020; 21(2):271–282 [9] Precision Oncology. 2021; 5:69
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