The Early Period in Genomics

 

Chat GPT4 Writes Article about New CRC Screening Studies

 In which I ask GPT4 to summarize two recent clinical reports in NEJM in the voice of a journalist. As its editor, I need to ask for a rewrite.   It does so. See my original blog.

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Attached are two primary clinical trials CHUNG and IMPERIALE, as well as an op ed over both, by Carethers.  You are a health care journalist.    Please write a news article for a health journal on the two clinical trials.  Your audience is people who work in health care or health policy.  You can borrow from Carethers for context but focus most of your news story and implications on othe CHUNG and IMPERIALE clinical trials.    Assume your readers are quite interested, but in the TLDR position.  Still, they want a granular idea of what's going on.

(TLDR, too long didn't read)

ChatGPT

In recent studies, two innovative colorectal cancer (CRC) screening tests have demonstrated significant potential in enhancing early detection and adherence to screening guidelines, key factors in reducing CRC mortality. These advancements represent a leap forward from traditional methods, offering new hope in the fight against the third most diagnosed cancer in adults in the United States.

The first study, the ECLIPSE trial, evaluated a cell-free DNA (cfDNA) blood-based test (Shield Guardant Health) designed to detect asymptomatic and early-stage CRC in a screening-eligible population. This non-invasive test, which examines cfDNA for genomic alterations, aberrant methylation, and fragmentation patterns, achieved a sensitivity of 83.1% for CRC detection and 89.6% specificity for advanced neoplasia, which includes CRC or advanced precancerous lesions. Its sensitivity for advanced precancerous lesions was 13.2%. The study's results suggest that this blood-based test, by simplifying the screening process to a routine blood draw, could potentially increase screening uptake, especially among diverse populations.

The second pivotal trial, known as the BLUE-C Study, conducted by Imperiale et al., focused on a next-generation multitarget stool DNA test. Building on the first-generation test, this updated version incorporates additional DNA biomarkers to detect CRC and advanced precancerous lesions. The study found that this new test preserved the sensitivity for CRC detection while improving specificity for the absence of any advanced neoplasia compared to its predecessor, promising a reduction in false-positive results and subsequent unnecessary follow-up colonoscopies.

These studies underscore a critical advancement in CRC screening technology. By offering less invasive, highly sensitive, and specific testing options, they address major barriers to screening adherence, including the invasiveness and inconvenience of traditional colonoscopies. The cfDNA blood-based test, in particular, represents a significant step towards integrating cancer screening into standard healthcare routines, potentially reaching a wider audience and ultimately saving lives through early detection.

The implications of these findings are profound for healthcare professionals and policymakers. As screening technologies evolve, so too must our strategies for integrating them into practice, ensuring that they are accessible and utilized effectively across diverse populations. These innovations in CRC screening hold the promise of transforming our approach to cancer prevention and care, moving us closer to the goal of reducing the burden of this disease on individuals and healthcare systems alike.

User

That's good, but a little too much hyperbole.   Avoid overly dramatic terms like "profound" and "a great leap forward."  Mind you the results are still good, and quite interesting, but not melodramatic.

ChatGPT RE-WRITE LESS DRAMATIC

Recent studies have introduced promising advancements in colorectal cancer (CRC) screening methods, which are crucial for early detection and improving survival rates. These developments offer new approaches to screening that could potentially enhance participation rates and the accuracy of CRC detection.

The ECLIPSE trial evaluated a cell-free DNA (cfDNA) blood-based test developed by Guardant Health. This test detects CRC by analyzing cfDNA for specific genomic alterations, methylation patterns, and DNA fragment changes. With a sensitivity of 83.1% for CRC and a specificity of 89.6% for advanced neoplasia, the test shows promise as a non-invasive, convenient option for CRC screening. Notably, its ability to be administered through a simple blood draw could make it easier to integrate into routine health check-ups, potentially increasing screening rates among various populations.

Another significant study, the BLUE-C trial, investigated a next-generation multitarget stool DNA test. This enhanced version of a previously available test includes additional DNA biomarkers to identify CRC and advanced precancerous lesions. The study findings suggest that the new test maintains high sensitivity for detecting CRC while improving specificity for excluding advanced neoplasia. This improvement could lead to fewer false positives and, consequently, reduce the need for unnecessary follow-up procedures like colonoscopies.

These studies contribute valuable information to the field of CRC screening. They introduce testing options that are less invasive and potentially more appealing to individuals who might be reluctant to undergo traditional screening methods such as colonoscopies. The cfDNA blood-based test, in particular, represents a notable advancement by offering a straightforward and accessible screening option.

For healthcare professionals and policymakers, these findings highlight the importance of continuing to explore and integrate innovative screening technologies. As these new methods are further validated and potentially adopted, they could play a significant role in improving CRC screening rates and outcomes. Overall, while the path to widespread implementation may require further research and logistical considerations, the progress indicated by these studies is an encouraging step forward in the ongoing effort to combat CRC.

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Finally describe the two rsearch articles from NEJM in the style of a rat-a-tat-tat 1930s newspaper room comedy, with fast-talking, interrupting, cigar chewin' journalists swigging from a flask, trading quips with eath other, while typing fast on their mechnical typewriters to get the story out , hot off the press, for the 3 pm special edition.

ChatGPT

[The sound of clacking typewriters fills the air, punctuated by the occasional ring of a phone and the low hum of urgent conversations. A cloud of smoke hovers over a room bustling with the chaotic energy of deadline day. A group of journalists, hats askew, sleeves rolled up, gather around a cluttered desk, papers strewn about, each vying for the next big scoop.]

Journalist 1: "Alright, folks, gather 'round! We got ourselves a pair of doozies hot off the presses from the boffins at NEJM. First up, Chung and the gang are shaking the trees with a blood test that's sniffing out colon cancer like a bloodhound on a T-bone steak!"

Journalist 2: [Typing furiously] "Bloodhound, you say? More like Sherlock Holmes with a microscope! 83.1% sensitivity, folks! This ain't your grandma's crystal ball. It's science, see?"

Journalist 3: [Puffing on a cigar, blowing smoke rings] "And don't you forget Imperiale's crew, with their stool DNA test. They're digging through... well, you know, to spot the big C before it knows it's been spotted. 93.9% sensitivity – it's like finding a needle in a haystack without even messing up the hay!"

Journalist 1: "Yeah, but here's the kicker, see? The blood test? It's as easy as drawing a pint at your local speakeasy. No more hoop-jumping with tubes and, uh, 'samples.' We're talking broad appeal, capisce?"

Journalist 2: [Glancing up from the typewriter] "And let's not give short shrift to specifics—89.6% specificity for the blood test and 90.6% for the stool test. This means fewer wild goose chases, fewer false alarms. We're on the level here, folks."

Journalist 3: "Say, what about the little guys? The precancers? Imperiale's test is pulling a 43.4% on catching those rascals before they crash the party. And Chung's test? Even throws in a bone with a 13.2%."

Journalist 1: "So what's the bottom line for our readers, eh?"

Journalist 2: [Takes a swig from the flask, then resumes typing] "The bottom line, my dear colleagues, is that the future's so bright, you gotta wear shades. These tests are changing the game—no ifs, ands, or buts. Screening's getting a facelift, and it's looking mighty fine, if I do say so myself."

Journalist 3: "Mighty fine indeed. But let's not count our chickens before they hatch. It's a big step, sure, but there's still miles to go before we sleep."

Journalist 1: "Alright, you mugs, back to the grind! We got a story to tell, and the clock's ticking. Let's give 'em the old razzle-dazzle, scoop of the century, see? On the double!"

[The room bursts into a frenzy of activity as the journalists dive back into their work, the clacking of typewriters now a symphony accompanying the relentless pursuit of news. The deadline looms, but the story of hope, of science triumphing over disease, will be told.]

[The camera pulls away, leaving behind the frenetic energy of the newsroom, as the screen fades to black.]

Chat GPT Compares ARPA H and NCATS

 What is ARPA H?

ChatGPT

ARPA-H, or the Advanced Research Projects Agency for Health, is an entity within the National Institutes of Health (NIH) focused on making pivotal investments in breakthrough technologies, platforms, capabilities, resources, and solutions with the potential to transform important areas of medicine and health. It aims to deliver transformative, sustainable, and equitable health solutions for everyone, driving biomedical and health breakthroughs through high-impact research. ARPA-H is designed to support ambitious projects that cannot readily be accomplished through traditional research or commercial activity, ensuring impactful expenditures and solutions that benefit the broader population​​​​.

User

How does it compare to the NIH institute for translational science?

ChatGPT

ARPA-H (Advanced Research Projects Agency for Health) and the NIH's National Center for Advancing Translational Sciences (NCATS) both aim to accelerate the process of turning scientific discoveries into health improvements, but they differ significantly in their approaches, focuses, and methods.

ARPA-H

Focus: ARPA-H is designed to drive breakthroughs in biomedicine and health through high-risk, high-reward research. It seeks to develop transformative health solutions by funding innovative and ambitious projects that may be too risky or unconventional for other funding mechanisms.

Approach: Modeled after the Defense Advanced Research Projects Agency (DARPA), ARPA-H emphasizes speed, flexibility, and the development of cutting-edge technologies. It aims to break down barriers to innovation and make significant leaps forward in health research and outcomes.

Projects: Likely to fund projects that develop new technologies, platforms, or systems that can lead to transformative changes in healthcare, focusing on rapid development and deployment.

NCATS (National Center for Advancing Translational Sciences)

Focus: NCATS focuses on translational science, aiming to speed up the process of turning scientific discoveries into diagnostic tools, medications, and treatments for patients. It addresses systemic issues that slow down the translational process to enhance the efficiency of developing and deploying new health solutions.

Approach: NCATS employs a broad approach to translational science, supporting research across the entire spectrum of translation, from basic research to clinical implementation. It works on improving the methods and technologies that support the translation of research into health benefits.

Projects: NCATS funds a wide range of projects that aim to improve the translational process, including drug development, clinical trial innovation, and the creation of research tools. It supports initiatives that remove bottlenecks in the development pipeline to make translational research more efficient and effective.

Comparison

Objective Alignment: Both ARPA-H and NCATS aim to improve health outcomes but focus on different stages and aspects of the research and development pipeline. ARPA-H is more about creating and leveraging breakthrough technologies and platforms for significant leaps in health research, while NCATS focuses on optimizing the translational research process to bring scientific discoveries to practical use more efficiently.

Risk Tolerance and Innovation: ARPA-H is likely to have a higher risk tolerance, focusing on potentially transformative projects with a higher degree of uncertainty. In contrast, NCATS might engage in a broader range of projects with varying levels of innovation and risk, emphasizing improving the overall translational research process.

In summary, while ARPA-H and NCATS share the ultimate goal of accelerating health improvements, they operate with different emphases and methodologies: ARPA-H on transformative technology and health solutions, and NCATS on streamlining and enhancing the translational science process.

User

Based on your knowledge above, can you give 2 projects that would be typical of ARPA and not NCATS, and conversely, 2 projects that would be typical of NCATS but not for ARPA.  I only expect imaginary examples but if you know of a real one that is OK to use.

ChatGPT

Certainly, I can provide hypothetical examples that illustrate the types of projects typically pursued by ARPA-H (Advanced Research Projects Agency for Health) and NCATS (National Center for Advancing Translational Sciences), keeping in mind their distinct objectives and approaches.

Typical ARPA-H Projects

Project QuantumVax: A revolutionary vaccine development platform using quantum computing to simulate and predict the effectiveness of vaccine candidates against rapidly mutating viruses. By leveraging the computational power of quantum computers, QuantumVax aims to dramatically reduce the time needed to develop vaccines for emerging diseases, potentially revolutionizing our response to pandemics. This project exemplifies ARPA-H's focus on high-risk, high-reward technologies that can transform health care.

NeuroLink Interface: A project aimed at creating a brain-computer interface (BCI) capable of restoring full motor function to individuals with severe spinal cord injuries. By developing cutting-edge neurotechnology and algorithms, NeuroLink Interface seeks to bypass damaged pathways, allowing for direct brain control of limb movements. This ambitious project highlights ARPA-H's interest in pioneering technologies that can lead to significant health advancements.

Typical NCATS Projects

Translational Toolkit for Rare Diseases: This initiative aims to develop a comprehensive set of tools and protocols designed to accelerate the discovery and development of treatments for rare diseases. By focusing on creating standardized models, databases, and biomarker identification processes, the Translational Toolkit seeks to overcome common bottlenecks in rare disease research, epitomizing NCATS's mission to enhance the efficiency of translational science.

Efficiency in Clinical Trials (ECT) Program: An initiative to innovate and improve clinical trial design, recruitment, and execution processes. The ECT Program could focus on developing novel patient recruitment strategies through AI and machine learning, creating adaptable trial protocols that can adjust in real-time based on interim results, and implementing remote monitoring technologies to reduce patient burden. This project reflects NCATS's role in streamlining translational research and making the clinical trial process more efficient and effective.

These examples illustrate the distinct focus areas of ARPA-H and NCATS: ARPA-H projects are characterized by their ambitious, transformative potential and high risk, aimed at making quantum leaps in health technology and solutions. In contrast, NCATS projects concentrate on improving the translational research infrastructure, making the path from discovery to treatment more efficient and effective, with a particular emphasis on systematic and process-oriented innovations.

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User

I did not think of ARPA H as being that techie.   I thought of it more as applied pragmatic trials whether A was better than B.   And more oriented to pragmatic trials than NIH.   But you are suggesting that with DARPA or BARDA as a model, ARPA would not only meet unmet needs but go high tech in the process.   

ChatGPT

Your perspective adds an important dimension to understanding ARPA-H's mission and potential scope of work. Indeed, while the analogy with DARPA or BARDA highlights the potential for high-tech innovation and transformative projects, ARPA-H's approach is also likely to encompass applied and pragmatic clinical trials to address pressing health challenges directly. This blend of ambitious tech-driven projects with practical, outcome-focused trials allows ARPA-H to tackle unmet needs in healthcare through a variety of strategies, including those that are less technology-intensive but highly impactful in terms of improving health outcomes.

Let's adjust the examples to reflect this broader vision:

ARPA-H Projects Aligned with Applied and Pragmatic Trials

Comparative Effectiveness Trial on Home-Based vs. Traditional Rehabilitation After Surgery: A large-scale, pragmatic clinical trial designed to evaluate the effectiveness, cost-efficiency, and patient satisfaction of home-based rehabilitation programs using telehealth and wearable devices against traditional, in-clinic rehabilitation services following orthopedic surgery. This project would address a practical question with significant implications for patient care and resource allocation in healthcare systems.

Community-Based Interventions for Diabetes Management: An applied research project testing the efficacy of community-based intervention programs compared to standard care in managing type 2 diabetes in high-risk populations. By leveraging local resources, education, and support networks, this trial aims to identify scalable and sustainable models for improving diabetes outcomes in underserved communities.

NCATS Projects with a Focus on Translational Science

To reiterate, NCATS typically focuses on:

Platform Technologies for Accelerating Gene Therapy Development: Developing and validating shared technology platforms that can be used across multiple gene therapy projects to speed up the early stages of therapy development. This could involve creating standardized viral vector libraries or automated cell line engineering processes, which would help reduce the time and cost of gene therapy research.

Adaptive Trial Designs for Personalized Medicine: Initiating projects that explore and validate adaptive clinical trial designs capable of evaluating personalized medicine approaches. This could include trials that adjust treatment strategies based on individual genomic or biomarker data in real-time, aiming to streamline the process of identifying the most effective treatments for specific patient subgroups.

Your comment rightly points out that ARPA-H's mission is expected to be diverse, not only advancing high-tech solutions but also addressing immediate and practical healthcare questions through innovative trial designs and interventions. This multifaceted approach enables ARPA-H to meet various unmet needs in the healthcare system, combining the pursuit of breakthrough technologies with the application of rigorous, evidence-based research to improve patient outcomes.