“Glucagon-like peptide-1 agonist (GLP-1) drugs have transformed type 2 diabetes care, but weekly injections can be burdensome for patients. A single shot a month could make it much easier for people living with diabetes or obesity to stick to their drug regimens, improving quality of life and reducing side effects and diabetes complications,” said lead author Dr Claire Mégret from ADOCIA, Lyon, France, the biotechnology company who developed the hydrogel.

Semaglutide works by mimicking the hormone glucagon-like peptide 1 (GLP-1), and is currently authorised for the treatment of type 2 diabetes patients with insufficient glycaemic control and long-term weight management.

Clinical studies suggest that adherence to injected semaglutide is 39-67% for type 2 diabetes patients at one year [1a], and 40% for patients who take the drug for weight loss [1b]. Similarly, adherence to daily oral pill formulations is around 40% at one year [2].

Long-acting delivery formulations could increase drug efficacy and safety by maintaining steady drug levels in the body at optimal concentrations.

The new hydrogel delivery platform uses two innovative degradable polymers that are chemically bound to one another to form a gel, but allow slow, sustained release of soluble peptides over 1 to 3 months.

“A small dollop of gel, known as a ‘depot,’ of the semaglutide-laden hydrogel is injected under the skin,” explained Dr Mégret. “The challenge is to formulate the hydrogel to entrap the peptides to limit initial burst (early release) of semaglutide molecules and, at the same time, to allow smooth release and controlled dissolving of the gel over one month, without generating toxic molecules.”

Several formulations of the hydrogel were tested in vitro to investigate the drug release rate, duration of action, and semaglutide load to define the best candidate.

The researchers found that the hydrogel could be easily injected using an off-the-shelf needle. Additionally, the gel started forming within minutes of mixing, ensuring sufficient time for the injection while minimising spread at the injection site, so that the depot is small enough to be comfortable and inconspicuous.

In vitro drug release assessments for all formulations showed extended and constant release rates over 1 to 3 months. The researchers also found that the release duration could be tailored through optimisation of the hydrogel properties and loading.

The hydrogel-semaglutide formulation was also tested in six laboratory rats. In the rats, a single injection of the hydrogel-based therapy, showed limited burst (early release) and a regular release over a one-month period.

Importantly, the hydrogel was well tolerated with no inflammatory reaction over the treatment period.

“Our pre-clinical results demonstrate that the regular, slow release of semaglutide over one month after administering a single dose, with limited early release, is achievable. Next we will be testing the hydrogel platform in pigs, whose skin and endocrine systems are most similar to those in humans. If that goes well, we will move forward the platform development by expecting clinical trials within the next few years,” said Dr Mégret.

The researchers will present their results at the fall meeting of the American Chemical Society (ACS). ACS Fall 2024 is a hybrid meeting being held virtually and in person Aug. 18-22; it features about 10,000 presentations on a range of science topics.

AI’s vast number of uses has made it almost ubiquitous in today’s technological landscape. However, many AI models are black boxes, meaning it’s not clear exactly what steps are taken to produce a result. And when that result is something like a potential drug molecule, not understanding the steps might stir up skepticism with scientists and the public alike. “As scientists, we like justification,” explains Rebecca Davis, a chemistry professor at the University of Manitoba. “If we can come up with models that help provide some insight into how AI makes its decisions, it could potentially make scientists more comfortable with these methodologies.”

One way to provide that justification is with XAI. These machine learning algorithms can help us see behind the scenes of AI decision making. Though XAI can be applied in a variety of contexts, Davis’ research focuses on applying it to AI models for drug discovery, such as those used to predict new antibiotic candidates. Considering that thousands of candidate molecules can be screened and rejected to approve just one new drug — and antibiotic resistance is a continuous threat to the efficacy of existing drugs — accurate and efficient prediction models are critical. “I want to use XAI to better understand what information we need to teach computers chemistry,” says Hunter Sturm, a graduate student in chemistry in Davis’ lab who’s presenting the work at the meeting.

The researchers started their work by feeding databases of known drug molecules into an AI model that would predict whether a compound would have a biological effect. Then, they used an XAI model developed by collaborator Pascal Friederich at Germany’s Karlsruhe Institute of Technology to examine the specific parts of the drug molecules that led to the model’s prediction. This helped explain why a particular molecule had activity or not, according to the model, and that helped Davis and Sturm understand what an AI model might deem important and how it creates categories once it has examined many different compounds.

The researchers realized that XAI can see things that humans might have missed; it can consider far more variables and data points at once than a human brain. For example, when screening a set of penicillin molecules, the XAI found something interesting. “Many chemists think of penicillin’s core as the critical site for antibiotic activity,” says Davis. “But that’s not what the XAI saw.” Instead, it identified structures attached to that core as the critical factor in its classification, not the core itself. “This might be why some penicillin derivatives with that core show poor biological activity,” explains Davis.

In addition to identifying important molecular structures, the researchers hope to use XAI to improve predictive AI models. “XAI shows us what computer algorithms define as important for antibiotic activity,” explains Sturm. “We can then use this information to train an AI model on what it’s supposed to be looking for,” Davis adds.

Next, the team will partner with a microbiology lab to synthesize and test some of the compounds the improved AI models predict would work as antibiotics. Ultimately, they hope XAI will help chemists create better, or perhaps entirely different, antibiotic compounds, which could help stem the tide of antibiotic-resistant pathogens.

“AI causes a lot of distrust and uncertainty in people. But if we can ask AI to explain what it’s doing, there’s a greater likelihood that this technology will be accepted,” says Davis.

Sturm adds that he thinks AI applications in chemistry and drug discovery represent the future of the field. “Someone needs to lay the foundation. That’s what I hope I’m doing.”

The research was funded by the University of Manitoba, the Canadian Institutes of Health Research and the Digital Research Alliance of Canada.

A Q&A with the researcher will be posted on Sunday, Aug. 18. Reporters can access the video during the embargo period, and once the embargo is lifted the same URL will allow the public to access the content. Visit the ACS Fall 2024 program to learn more about this presentation, “Using Explainable Artificial Intelligence to explore the relationship between structure and activity,” and other science presentations.

This research was presented at a meeting of the American Chemical Society. ACS does not conduct research, but publishes and publicizes peer-reviewed scientific studies.

A paper released today titled “Modeling impact of Inflation Reduction Act price negotiations on new drug pipeline considering differential contributions of large and small biopharmaceutical companies,” published in the journal Clinical Trials, showed that for large pharmaceutical producers, which account for the large majority of product sales, revenue, and profit, the level of R&D spending was strongly related to revenue from 2000-2018. In contrast, for smaller biotechnology companies, which typically have few products and little revenue but sponsor the majority of all clinical trials, there was no relationship between R&D spending and revenue. These companies typically acquire capital for R&D substantially through new investment in equity offerings.

This research also assessed the impact of reducing drug pricing on the number of new drug approvals using a drug development pipeline model that considers the differential contributions of large and small companies and likely changes in R&D spending in response to changes in revenue. This analysis suggests the current level of drug approvals could be maintained in the face of global revenue reductions of up to 10% through strategic distribution of cost reductions in large companies between early and late phases of clinical development, coupled with continued acquisition of candidate products in early phases of development by biotechnology companies.

A related working paper titled “Implications of the Inflation Reduction Act for the biotechnology industry; sensitivity of investment and valuation to drug price indices and market conditions,” published by the Institute for New Economic Thinking, showed that there was no relationship between investment in biotechnology and indices of drug prices 2000-2020. This suggests that investment in biotechnology companies is unlikely to be affected by decreases in drug prices and will continue to provide the capital necessary for early-stage innovation and development in biotechnology companies.

These studies describe a dynamic innovation process in which small, emerging biotechnology companies originate the majority of new products and sponsor the majority of all clinical trials with innovation capital arising from private or public investment. These products may then be developed by the biotechnology companies themselves or acquired by large pharmaceutical companies for late-stage development and commercialization. The analysis suggests that the industry can sustain current levels of product approval and commercialization without compromising corporate earnings or investor returns.

These studies do not support industry arguments that drug price reductions anticipated by the IRA represent a threat to corporate profits, investor returns, or new product approvals.

“Pharmaceutical innovation is not adequately described by conventional economic theories that fail to account for the distinct business models of small, science-based biotechnology companies” said Fred Ledley, Director of the Center for Integration of Science and Industry, and the senior author on these studies. “Our work suggests that established management and investment practices could preserve both the industry’s profits and current levels of drug approvals in face of the reductions in drug price anticipated by the Inflation Reduction Act.”

Dr. Gregory Vaughan, Associate Professor of Mathematical Sciences at Bentley University, was the lead author of the publication in Clinical Trials along with Roger Du and Dr. Ledley. Dr. Cody Hyman, Assistant Professor of Accounting at Bentley University, was the lead author of the working paper published by INET along with Henry Dao, Dr. Vaughan, and Dr. Ledley. Roger Du and Henry Dao worked as undergraduate researchers at Bentley University.

This work was funded by the West Health Policy Center and National Biomedical Research Foundation through grants to Bentley University.

A new study led by Duke Health shows that over half of the medicines stocked in space — staples such as pain relievers, antibiotics, allergy medicines, and sleep aids — would expire before astronauts could return to Earth.

Astronauts could end up relying on ineffective or even harmful drugs, according to the study appearing July 23 in npj Microgravity, a Nature journal.

“It doesn’t necessarily mean the medicines won’t work, but in the same way you shouldn’t take expired medications you have lying around at home, space exploration agencies will need to plan on expired medications being less effective,” said senior study author Daniel Buckland, M.D., Ph.D., an assistant professor of emergency medicine at Duke University School of Medicine and an aerospace medicine researcher.

Expired medications can lose their strength by a little – or a lot. The actual stability and potency of medications in space compared to Earth remain largely unknown. The harsh space environment, including radiation, could reduce the effectiveness of medications.

Buckland and co-author Thomas E. Diaz, a pharmacy resident at The Johns Hopkins Hospital, noted that expired medications could pose a challenge as space agencies plan for long-duration missions to Mars and beyond.

Diaz used a Freedom of Information Act Request to obtain information about the space station formulary, assuming NASA would use similar medications for a Mars mission.

Using a database of international drug expiration dates, the researchers determined that 54 of the 91 medications had a shelf-life of 36 months or less.

Using the most optimistic estimates, about 60% of these medications would expire before a Mars mission concludes. Under more conservative assumptions, the figure jumps to 98%.

The study did not assume accelerated degradation but focused on the inability to resupply a Mars mission with newer medicines. This lack of resupply affects not only medications but also other critical supplies, such as food.

Increasing the number of medications brought on board could also help compensate for lowered efficacy of expired meds, authors said.

“Those responsible for the health of space flight crews will have to find ways to extend the expiration of medications to complete a Mars mission duration of three years, select medications with longer shelf-lives, or accept the elevated risk associated with administering expired medication,” Diaz said.

“Prior experience and research show astronauts do get ill on the International Space Station, but there is real-time communication with the ground and a well-stocked pharmacy that is regularly resupplied, which prevents small injuries or minor illnesses from turning into issues that affect the mission,” Buckland said.

Additional authors include Emma Ives and Diana I. Lazare. The study received no external funding.

The committee recommended authorisation for the following:

Balversa (erdafitinib) for the treatment of adult patients with unresectable or metastatic urothelial carcinoma, a cancer of the bladder and urinary system.

Eurneffy (epinephrine), the first emergency treatment against allergic reactions that is administered as a nasal spray, not as an injection.

mResvia (Respiratory Syncytial Virus (RSV) mRNA vaccine) for prevention in adults 60 years of age and older of lower respiratory tract disease and acute respiratory disease caused by respiratory syncytial virus (RSV). RSV is a common respiratory virus that usually causes mild, cold-like symptoms but can lead to serious consequences in older adults. This is the first mRNA vaccine targeting a different pathogen than SARS-CoV-2 that receives a positive opinion from the CHMP.

Ordspono (odronextamab) received a conditional recommendation for the treatment of follicular lymphoma and diffuse large B-cell lymphoma, two types of blood cancer that affect the immune system.

Piasky (crovalimab) for the treatment of paroxysmal nocturnal haemoglobinuria, a rare genetic disorder that causes the premature breakdown of red blood cells by the immune system and is potentially life-threatening.

Tauvid (flortaucipir (¹⁸F)) for positron emission tomography (PET) imaging of the brain in adult patients with cognitive impairment who are being evaluated for Alzheimer’s disease.

Winrevair (sotatercept) to treat adult patients with pulmonary arterial hypertension, a rare, long-term, debilitating and life-threatening condition in which patients have abnormally high blood pressure in the arteries in the lungs.

Steqeyma (ustekinumab), a biosimilar medicine for the treatment of adult patients with moderate/severe active Crohn’s disease, plaque psoriasis, paediatric plaque psoriasis and psoriatic arthritis.

The committee also adopted positive opinions for two generic medicines: Enzalutamide Viatris (enzalutamide) for the treatment of prostate cancer, and Nilotinib Accord (nilotinib) for the treatment of Philadelphia chromosome positive chronic myelogenous leukaemia.

Extensions of indication were recommended for 11 medicines that are already authorised in the EU: Betmiga, Beyfortus, Cresemba, Imcivree, Imfinzi, Infanrix hexa, Lynparza, Pegasys, Tepkinly, Vabysmo and Xalkori.

Researchers from the University of Nottingham’s, Centre for Additive Manufacturing have led research alongside the School of Pharmacy that has fabricated personalised medicine using Multi-Material InkJet 3D Printing (MM-IJ3DP). The research has been published in Materials Today Advances.

The team have developed a cutting-edge method that enables the fabrication of customised pharmaceutical tablets with tailored drug release profiles, ensuring more precise and effective treatment options for patients.

Using Multi-Material InkJet 3D Printing (MM-IJ3DP), tablets can be printed that release drugs at a controlled rate, determined by the tablet’s design.  This is made possible by a novel ink formulation based on molecules that are sensitive to ultraviolet light. When printed, these molecules form a water-soluble structure.

The drug release rate is controlled by the unique interior structure of the tablet, allowing for timing the dosage release. This method can print multiple drugs in a single tablet, allowing for complex medication regimens to be simplified into a single dose.

Dr Yinfeng He, Assistant Professor in the Faculty of Engineering’s Centre for Additive Manufacturing led the research, he said: “This is an exciting step forwards in the development of personalised medication. This breakthrough not only highlights the potential of 3D printing in revolutionizing drug delivery but also opens up new avenues for the development of next-generation personalized medicines.”

“While promising, the technology faces challenges, including the need for more formulations that support a wider range of materials. The ongoing research aims to refine these aspects, enhancing the feasibility of MM-IJ3DP for widespread application.” Professor Ricky Wildman added.

This technology will be particularly beneficial in creating medication that needs to release drugs at specific times, making it ideal for treating diseases, where timing and dosage accuracy are crucial. The ability to print 56 pills in a single batch demonstrates the scalability of this technology, providing a strong potential for the production of personalised medicines.

Professor Felicity Rose at the University of Nottingham’s School of Pharmacy was one of the co-authors on the research, she says: “The future of prescribed medication lies in a personalised approach, and we know that up 50% of people in the UK alone don’t take their medicines correctly and this has an impact on poorer health outcomes with conditions not being controlled or properly treated. A single pill approach would simplify taking multiple medications at different times and this research is an exciting step towards that.”

IMAGE: 3D PRINTED PILL USING NEW TECHNIQUE

view more CREDIT: UNIVERSITY OF NOTTINGHAM, CENTRE FOR ADDITIVE MANUFACTURING

About three million people in the U.S. have glaucoma, a group of diseases that damage the optic nerve and lead to vision loss, according to the Centers for Disease Control and Prevention. Doctors use flinch-inducing “air puff tests” during eye exams to take one-time measurements of eye pressure. A slight elevation in pressure, an otherwise imperceptible symptom caused by fluid buildup around the cornea, can lead to a glaucoma diagnosis. Researchers have been testing ways to continuously and more comfortably detect these tiny fluctuations in pressure, such as contact lenses that transmit signals to receptor glasses. However, changing temperatures — like stepping outside into cold weather — can throw off the lenses’ measurements. So, Dengbao Xiao and coworkers wanted to develop a contact lens that accurately measures and wirelessly transmits real-time signals about eye pressure across a wide range of temperatures.

First, Xiao and the team designed two miniature spiral circuits, each with a unique natural vibration pattern that would change when stretched by minute amounts, such as with changes to an eye’s pressure and diameter. To create pressure-detecting contact lenses, the researchers sandwiched these tiny circuits between layers of polydimethylsiloxane, a typical contact lens material. Then they wirelessly read the embedded circuits’ vibration patterns by holding a coil near the lens that was connected to a computer. The transmitted signals were unaffected by tests meant to mimic eye movement, extended exposure to moisture (to simulate damp conditions in the eye), and daily wear and tear.

In laboratory tests, the researchers placed the new lenses on three individual pig eye specimens while controlling the ocular pressures and temperatures. The contact lenses monitored and wirelessly transmitted pressure data from 50 to 122 degrees F. When pressures were calculated from the signal of only one circuit in the lens, the results deviated up to 87% from the true values. However, when information from both circuits was used, the pressure readings differed by only 7% from the true value because the combination removed temperature-related errors. The researchers say that their dual-circuit “smart” lens design has potential to be used for accurate early detection and monitoring of glaucoma, even in a wide range of temperatures.

The authors acknowledge funding from the National Natural Science Foundation of China.

IMAGE: THIS “SMART” CONTACT LENS COULD SOMEDAY HELP MEASURE EYE PRESSURE AND SEND WIRELESS SIGNALS TO ENABLE EARLY DETECTION OF GLAUCOMA.

view more CREDIT: ADAPTED FROM ACS APPLIED MATERIALS & INTERFACES 2024, DOI: 10.1021/ACSAMI.4C02289

Zhou is an associate professor in the Department of Industrial and Molecular Pharmaceutics, a Faculty Scholar and a faculty member of the Purdue Institute for Drug Discovery and the Purdue Institute of Inflammation, Immunology and Infectious Disease. He leads a team of multinational experts from Australia, Thailand and the United States in developing novel, patent-pending inhalation therapeutics for lung infections.

“We are providing a promising option to fight the global crisis of antimicrobial resistance,” Zhou said. “The successful development of our invention could save tens of thousands of lives from a variety of deadly lung infections, including cystic fibrosis and ventilator-assisted pneumonia.”

Zhou’s research in antimicrobial resistance has yielded two U.S. patents, four patent applications and more than 70 publications in peer-reviewed journals. The most recent peer-reviewed journal publications were in Pharmaceutics in March 2024 and Pharmaceutical Research in August 2022.

With the latest NIH grant, Zhou has now received six federal grants totaling $10 million, including three NIH R01 grants in the past eight years to support the inhalation therapeutics research.

The threat of antimicrobial resistance

Thomas Sors, director of scientific strategy and relations at the Purdue Institute of Inflammation, Immunology and Infectious Disease, said antimicrobial resistance represents a severe global health threat as pathogens increasingly evade traditional treatments.

“The Centers for Disease Control and Prevention note that each year in the U.S., drug-resistant infections affect over 2.8 million individuals and result in more than 35,000 deaths, highlighting the urgent need for innovative strategies to address this crisis,” Sors said.

“According to the NIH, CDC and the Infectious Diseases Society of America, gram-negative ‘superbugs’ such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii rank among the most dangerous multidrug-resistant microorganisms. Regrettably, the development of new antibiotics is lagging, and lung infections triggered by these resistant pathogens can be fatal.”

Developing inhalation therapeutics for the lungs

Zhou said oral or intravenous administrations of many antibiotics are often not effective for treatment of lung infections in many patients due to very limited drug exposure at the infection site and systemic toxicity.

“This makes lung infections caused by resistant bacteria extremely difficult to treat, reflected by the fact that lung infections are the fourth leading cause of death in the world,” Zhou said.

Zhou’s inhalation therapeutics help antibiotics directly reach the infection site in the lungs to better kill the bacteria. Inhaled medicines also can avoid systemic toxicity because much fewer drugs are absorbed into the bloodstream.

“We also use the innovative manufacturing techniques of advanced spray drying to incorporate two or more synergistic antibiotics into a single particle so they can deposit at the same site of infection and achieve the maximum bacterial killing synergy,” he said.

Next development steps

Preliminary animal studies showed superior bacterial killing capability and reduced toxicity of the new inhalation medicines.

Zhou said the team’s goal is to develop viable pharmaceutical products to effectively treat resistant bacterial lung infections. The NIH funding will be utilized to optimize the formulation and generate preclinical data for potential filing of a New Drug Application.

“Zhou’s cutting-edge research is a true breakthrough and perfectly exemplifies Purdue’s commitment to fight the global crisis of antimicrobial resistance,” said Eric Barker, the Jeannie and Jim Chaney Dean of Purdue’s College of Pharmacy.

Zhou disclosed the inventions of inhalation medicines to the Purdue Innovates Office of Technology Commercialization, which has applied for patents to protect the intellectual property. Industry partners interested in developing or commercializing the work should contact Joe Kasper, assistant director of business development and licensing — life sciences, at jrkasper@prf.org.

Writer/Media contact: Steve Martin, sgmartin@prf.org

Writer: Jenn Stewart-Burton, jsstewar@purdue.edu

Source: Tony Zhou, tonyzhou@purdue.edu

IMAGE: PURDUE UNIVERSITY’S QI “TONY” ZHOU LEADS A TEAM OF MULTINATIONAL EXPERTS TO DEVELOP NOVEL, PATENT-PENDING INHALATION THERAPEUTICS FOR LUNG INFECTIONS. HE RECEIVED A $2.4 MILLION GRANT FROM THE NATIONAL INSTITUTES OF HEALTH, AND THE RESEARCH WAS PUBLISHED IN THE MARCH 2024 ISSUE OF PHARMACEUTICS.

view more CREDIT: PHOTO PROVIDED BY TONY ZHOU

To address this challenge, investigators from Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system, recently developed and validated a computer program that can be incorporated into electronic medical record systems to help clinicians diagnose mpox (formerly known as monkeypox).

The research is published in Infection Control and Healthcare Epidemiology.

“We built a novel decision support tool embedded in the electronic medical record that guides clinicians on crucial features of the physical examination and on important questions to ask patients with possible mpox,” said lead author Jacob Lazarus, MD, PhD, a physician investigator in the Division of Infectious Diseases within Massachusetts General Hospital’s Department of Medicine, and an instructor in Medicine at Harvard Medical School.

The clinical decision support system, called EvalMpox, proved useful in patients presenting to medical care with a rash. Its utility was assessed in 668 patient visits from more than 100 clinical locations across Greater Boston, Nantucket, Martha’s Vineyard, western Massachusetts, and southern New Hampshire.

EvalMpox guided clinicians in asking patients about potential mpox exposures, about symptoms of mpox, and in performing a physical examination to look for the characteristic mpox rash. EvalMpox was then able to use these answers to classify a patient as “likely to have mpox” or “unlikely to have mpox.”

The investigators found that the patients deemed likely to have mpox had similar characteristics compared with patients confirmed to have mpox. These patients were then prioritized for testing, and they were significantly more likely to test positive for mpox than patients deemed unlikely to have mpox.

“Our program identified nearly all cases of mpox diagnosed in the MGB system during the study period, underscoring the value of clinical decision support tools in assisting clinicians with early identification, isolation, and management of patients with communicable diseases like mpox,” said senior author Erica S. Shenoy, MD, PhD, Chief of Infection Control for Mass General Brigham and an associate professor of Medicine at Harvard Medical School.

The tool also had a high negative predictive value, meaning that if EvalMpox indicated that a person was low risk for mpox, it was very unlikely that they had the infection. “The tool’s high negative predictive value is also important,” emphasized Dr. Shenoy. “While the importance of early identification and isolation to prevent risk of transmission of disease cannot be overemphasized, we also know that it is critically important to have efficient ways to determine when isolation can be discontinued, and to reassure patients that they are unlikely to have an infection.”

Similar tools may help to assist clinicians in the identification, evaluation, and management of diverse infectious diseases now and in the future.

“Leveraging insights gained during the COVID-19 pandemic and the mpox outbreak, we are developing new decision support tools for diagnosing other emerging infections such as Ebola, Lassa Fever, and Marburg Virus Disease, as well as to support evaluation and management of patients with more ‘routine’ infections that impact delivery of healthcare based on requirements for patient isolation,” said Lazarus.

Authorship:

Jacob E. Lazarus, MD, PhD, Chloe V. Green, MURP, Michelle S. Jerry, BS, Lindsay Germaine, MPH, Dustin S. McEvoy, BS, Caitlin M. Dugdale, MD, MSc, Kristen M. Hysell, MD, MPH, Rebecca L. Craig, RN, MPH, CIC, Molly L. Paras, MD, Howard M. Heller, MD, MPH, Kevin L. Ard, MD, MPH,  John S. Albin, MD, PhD, Hang Lee, PhD, and Erica S. Shenoy, MD, PhD.

Funding:

This work was supported by a cooperative agreement from the Centers for Disease Control and Prevention. The Centers for Disease Control and Prevention had no involvement in the preparation, submission, or review of the manuscript.

Paper cited:

Lazarus J et al.  “Separating the Rash from the Chaff: Novel Clinical Decision Support Deployed During the Mpox Outbreak” Infection Control and Healthcare Epidemiology DOI: https://doi.org/10.1017/ice.2024.51

“For years, the debate has centred on how to improve the efficiency of healthcare. Thanks to advances in generative AI and language modelling, there are now opportunities to reduce the administrative burden on healthcare professionals. This will allow doctors to spend more time with their patients,” explains Cyrus Brodén, an orthopaedic physician and researcher at Uppsala University Hospital and Uppsala University.

Administrative tasks take up a large share of a doctor’s working hours, reducing the time for patient contact and contributing to a stressful work situation. Researchers at Uppsala University Hospital and Uppsala University, in collaboration with Danderyd Hospital and the University Hospital of Basel, Switzerland, have shown in a new study that the AI model ChatGPT can write administrative medical notes up to ten times faster than doctors without compromising quality.

The aim of the study was to assess the quality and effectiveness of the ChatGPT tool when producing medical record notes. The researchers used six virtual patient cases that mimicked real cases in both structure and content. Discharge documents for each case were generated by orthopaedic physicians. ChatGPT-4 was then asked to generate the same notes. The quality assessment was carried out by an expert panel of 15 people who were unaware of the source of the documents. As a secondary metric, the time required to create the documents was compared.

“The results show that ChatGPT-4 and human-generated notes are comparable in quality overall, but ChatGPT-4 produced discharge documents ten times faster than the doctors,” notes Brodén.

“Our interpretation is that advanced large language models like ChatGPT-4 have the potential to change the way we work with administrative tasks in healthcare. I believe that generative AI will have a major impact on healthcare and that this could be the beginning of a very exciting development,” he maintains.

The plan is to launch an in-depth study shortly, with researchers collecting 1,000 medical patient records. Again, the aim is to use ChatGPT to produce similar administrative notes in the patient records.

“This will be an interesting and resource-intensive project involving many partners. We are already working actively to fulfil all data management and confidentiality requirements to get the study under way,” concludes Brodén.

Rosenberg, G. S., Magnéli, M., Barle, N., Kontakis, M. G., Müller, A. M., Wittauer, M., Gordon, M., & Brodén, C.. 2024: ChatGPT-4 generates orthopedic discharge documents faster than humans maintaining comparable quality: a pilot study of 6 cases. Acta Orthopaedica, 95, 152-156. https://doi.org/10.2340/17453674.2024.40182

The study from Bentley University’s Center for Integration of Science and Industry titled “Association between expedited review designations and the US or global burden of disease for drugs approved by the US Food and Drug Administration 2010-2019: a cross-sectional analysis” used metrics developed by the World Health Organization (WHO) to measure the years of life lost (YLL), years of healthy life lost with disability or ill health (YLD), and total disease burden (disability-adjusted life years, DALYs) associated with the conditions treated by the 387 drugs approved by the FDA from 2010-2019.

This research showed that the majority of drug approvals were indicated for conditions in the highest quartile of US disease burden and years of life lost. In contrast, only a quarter of these approvals were indicated for conditions in the highest quartile of global disease burden or years of healthy life lost with disability or ill health. There was no alignment between the indications for approved drugs and either US or global disability. Since the US burden of disease represents <4% of the global disease burden, these data indicate that there is little alignment between the drugs being developed by the global pharmaceutical industry and the health needs of global human populations.

The four expedited review programs in the US – fast track, breakthrough therapy, accelerated approval, and priority review – are each designed to reduce the timelines or costs of developing products for selected “serious” diseases and have been widely adopted by industry. The present study shows that the likelihood of a drug receiving one or more designations for expedited approval was lower for products indicated for conditions with greater burden of disease in US or global populations and was dramatically lower for products targeting the greatest years of healthy life lost with disability or ill health.

“Product development by global pharmaceutical companies is strongly influenced by potential sales in US markets, and companies typically see little commercial opportunity in developing products for diseases that primarily afflict low- or middle-income countries” said Dr. Fred Ledley, Director of the Center for Integration of Science and Industry and Professor of Natural & Applied Sciences and Management at Bentley University. “If expedited review programs disproportionately reduce the cost of developing products indicated for conditions with lower disease burden, this could inadvertently disincentivize development of products that address the greatest burden of human disease.”

This paper is one of a series from the Center for Integration of Science and Industry examining the public sector investment and impacts of drugs approved by the FDA from 2010-2019.

Dr. Matthew Jackson, a former fellow at the Center for Integration of Science and Industry, was the lead author of this study along with Dr. Gregory Vaughan, Associate Professor of Mathematical Sciences, and Dr. Ledley.

This work was supported by grants from the Institute for New Economic Thinking and National Biomedical Research Foundation to Bentley University.

THE CENTER FOR INTEGRATION OF SCIENCE AND INDUSTRY at Bentley University focuses on advancing the translation of scientific discoveries to create public value. The Center is an environment for interdisciplinary scholarship spanning science, data analytics, business, and public policy. For more information, visit www.bentley.edu/sciindustry and follow us on Twitter/X @sciindustry and LinkedIn. The Center for Integration of Science and Industry is an affiliate of the Center for Health and Business at Bentley University.

BENTLEY UNIVERSITY is one of the nation’s top business schools and a lifelong-learning community that creates successful leaders who make business a force for positive change. With a combination of business and the arts and sciences and a flexible, personalized approach to education, Bentley provides students with critical thinking and practical skills that prepare them to lead successful, rewarding careers. Founded in 1917, the university enrolls >4,000 undergraduate, graduate, or PhD students and is set on 163 acres in Waltham, Massachusetts, 10 miles west of Boston. For more information, visit bentley.edu. Follow us on Twitter/X @BentleyU #BentleyUResearch.

IMAGE: NUMBER OF FDA DRUG APPROVALS 2010-2019 FOR CONDITIONS RANKED BY LOWEST-HIGHEST US (BLUE) OR GLOBAL (ORANGE) BURDEN OF DISEASE. THE BURDEN OF DISEASE IS MEASURED BY DALYS, YLL OR YLD. THE NUMBER OF FDA APPROVALS IS SHOWN FOR NEOPLASTIC (PATTERNED FILL) AND NON-NEOPLASTIC (SOLID FILL) CONDITIONS.

view more CREDIT: BENTLEY UNIVERSITY

A family of pharmacological targets, on which approximately 35% of FDA-approved drugs work, consists of receptors at the surface of cells named “G protein coupled receptors” or GPCRs. These membrane proteins sense a wide variety of signals from outside the cell, from hormones to neurotransmitters, or light and odors, to trigger responses of cells, from immune reactions to muscle contraction.

In a new study, researchers at Boston University Chobanian & Avedisian School of Medicine describe the development of a new technological platform that will enhance the accuracy and efficiency of drug discovery related to a large family of important pharmacological targets, i.e., GPCRs, allowing it to obtain information that was previously unattainable.

“The new technological platform are biosensors that allow us to detect the activity of GPCRs in their native cellular context and in real time not only with unprecedented fidelity, but also with relative ease. A novelty of this platform is that it is easy for others to implement and that it has been made readily available through a public repository such as open-source,” explains Remi Janicot, first author of the study and a PhD student in the laboratory of Mikel Garcia-Marcos, PhD, professor of biochemistry and cell biology at the school.

The researchers used molecular engineering to create these biosensors, artificial genes that, once expressed as proteins in cells, could detect the activation of very specific cellular responses in real time. The researchers then showed that these biosensors could be leveraged to characterize how many different natural ligands and synthetic drugs change cell responses when the act on the large GPCR class of receptors.

According to the researchers, the biosensor platform described could accelerate drug development for any disease in which GPCRs are implicated, which is a virtually endless list covering neurodegenerative disorders, cancers, cardiovascular diseases, obesity, or asthma, to name a few. “For example, the ongoing interest in developing safer opioid or non-opioid analgesics would benefit from the features of the technology described in our work. Similarly, there is tremendous interest in developing orally bioavailable substitutes for the anti-obesity drugs commercialized as Ozempic and Wegovy, which would also benefit from the technology we described,” said Garcia-Marcos.

The researchers hope the tools developed in this study will transform how the field of pharmacology and drug development approaches the investigation of a large and important class of targets. “Since medicines acting on these targets are already part of everyday life, we see great potential on accelerating the discovery of improved drugs for many different indications, from analgesia to anti-obesity drugs,” added first author and PhD student Remi Janicot.

These findings appear online in the journal Cell.

Funding was provided by NIH grant R01GM147931 (to MG-M) and grant R01NS117101 (to MG-M). RJ is supported by a Predoctoral Fellowship from the American Heart Association (898932). AL is supported by a F31 Ruth L. Kirschstein NRSA Predoctoral Fellowship (F31NS115318). JZ was supported by a Dahod International Scholar Award. HZ was supported by the American Heart Association (23CDA1050577).