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AI, big data and real world evidence – the challenges and opportunities

Real-world evidence (RWE) is emerging as an important area of research to reveal, in real time, new insights
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Real-world evidence (RWE) is emerging as an important area of research to reveal, in real time, new insights and innovations in medicine.

A recent pharmaphorum webinar, held in partnership with Savana and BREATHE – the Health Data Research Hub for Respiratory Health, heard that RWE is also accelerating the development of new and innovative therapies and treatments to improve patient outcomes.

But, until recently, an important data source has been locked up in the electronic health record (EHR), often in the form of unstructured or ‘free’ text entered by healthcare professionals.

This had previously been difficult to analyse and interpret for the purpose of health research. Now, artificial intelligence (AI) techniques such as natural language processing (NLP) and machine learning are helping clinicians unlock this valuable, unstructured information.

The webinar explored the potential of the technology to process the vast amount of data languishing untapped in EHRs, while ensuring that patient data privacy and safety is maintained at all times.

Opportunities are growing for real-world evidence research as the technology matures and a pioneering new partnership between Savana, utilising its AI-driven clinical research methodology, and BREATHE aims to drive innovative research using this new way of working.

The benefits of RWE

One of the main reasons to use RWE is to counter a common criticism of the large phase 3 trials that for so long have been the ‘gold standard’ when developing drugs and gaining authorisations from regulators.

Patients in the trials are carefully selected to make sure their disease is a good fit, but it is often said that they don’t effectively capture the kind of outcomes that will be seen in the real-world once a drug is launched in the general population.

Professor Jenni Quint, deputy director of BREATHE, outlined that much of the RWE in the UK comes from the electronic health record, particularly in primary care, where for some time every single encounter between primary care professionals and their patients has been recorded and stored.

“They are updated regularly and they cover longer periods of time. So not only are you able to get real-time updates in terms of what happens within clinical practice, you can also look at things longitudinally,” she said.

“Health data is essential for helping us deliver better patient outcomes and in particular with BREATHE in mind, we are really interested in improving the lives of people with underlying respiratory conditions.”

Great data, but difficult to find, access and use

While the UK has some of the best data sets in the world thanks to this electronic health record, Quint said there are challenges using it for research purposes, in particular where vital information is contained in an unstructured form.

“Data can be difficult to find and difficult to access and equally very difficult to use,” she told the webinar.

BREATHE and Savana are working together to overcome this with a new research methodology that uses de-identified patient data to provide insight into respiratory diseases using cutting-edge techniques.

The partnership draws on Savana’s AI technology and clinical research methodology which can analyse both structured and unstructured data in the free text of EHRs.

This can then be used to monitor disease progression and outcomes in patients hospitalised with COVID-19 and is combined with natural language processing (NLP), a machine learning analysis method.

Dr Ignacio Medrano, chief medical officer and founder at Savana, said: “We are now able to teach a computer how to read records and turn free text into a database of clinical variables.”

Data collected like this is also acceptable to regulators, pointed out Medrano, meaning that it can be used during the clinical development process.

It can overcome language barriers as a translation system has been built into the technology and it can be used at scale to pull together large amounts of data.

“Data can be difficult to find and difficult to access and equally very difficult to use”

 

Using real-world data in real life

Quint outlined how BREATHE is working with Savana’s AI technology to analyse both structured and unstructured data from hospitals records in the BigCOVIData study.

“The BigCOVIData study will allow us to predict COVID-19 progression and outcomes, helping hospitals to prepare for and monitor future waves of the virus,” according to Quint.

She went on to describe another study, EAVE II, which has drawn on BREATHE’s expertise, linking patient data across the entire Scottish population to provide the first real-world evidence of the success of the COVID-19 vaccination programme in cutting risk of hospital admission.

Prospective RWE studies in people who are at risk of developing a condition, allow researchers to gauge the impact of a therapy at a population level and are becoming increasingly common.

They allow them to study the development of disease in a group of patients that are more representative of the general population than in a typical clinical trial, giving a more nuanced view of the performance of the therapy’s benefits and drawbacks.

Patient-friendly studies

Professor Nawar Bakerly, a consultant respiratory physician at Salford Royal NHS Foundation Trust, referenced the ground-breaking Salford Lung Study, one of the first large-scale RWE-based studies, to describe the challenges and opportunities of collecting data in these sorts of studies in the NHS.

The study measured the impact of next generation inhaled lung drugs on COPD and he said it had a lower drop-out rate than other similar studies. Just 7% of patients left the study, compared with up to 44% in another COPD project, thanks to a study design that relied on evidence collected from electronic records rather than by requiring patients to attend hospitals or clinics for tests.

“It’s less cumbersome on patients – we don’t have to bring patients for these frequent visits that they have to attend in the usual way with randomised controlled trials.”

Bakerly also noted that the separate OpenSafely initiative had been used to interrogate NHS data to gain insights into COVID-19 related deaths in the pandemic.

While the focus of the webinar was on respiratory diseases, RWE evidence can be used in other illnesses too, with potential for the approach to be used to improve care in areas such as rare diseases, according to the panellists.

The challenge with rare diseases is to link up data from patients scattered across the globe, something that was extremely difficult without AI techniques, they said in a concluding question and answer session.

Savana’s Ignacio Medrano said that the company was already active in this area and has been able to conduct ‘deep screening’ for patients who are undiagnosed.

The system can put a ‘red flag’ on the patients who could benefit from a test, although the system is not intended to make a direct diagnosis.

“We are doing that with a good number of rare diseases already both in respiratory diseases and neurology with different life sciences companies in different countries.”

Wearables, smartphones and apps could also be used to gather RWE in studies involving round-the-clock monitoring of patients.

BREATHE’s Jenni Quint said that the power is not just in information from wearables but the ability to link them with other data.

This idea of mixing information from other sources, such as pollution data, could give insights into causes of disease and potential therapies.

“Every single piece of data adds to the bigger picture,” Quint concluded.

About the webinar panel

Dr Ignacio H Medrano, CMO and founder, Savana is a consultant neurologist with training in healthcare management and experience in clinical research strategies – formerly responsible for +500 researchers. A Singularity University graduate, he is also a founder at Mendelian in the UK which is utilising AI in the diagnosis of rare diseases. Ignacio is in demand as an international speaker at digital health, clinical research, science and technology events and congresses.

Professor Jenni Quint, deputy director, BREATHE – the Health Data Research Hub for Respiratory Health, is currently a Professor of Respiratory Epidemiology at the National Heart and Lung Institute (NHLI), Imperial College London and an Honorary Consultant. She currently also leads a clinical epidemiology research group, partners with the Royal College of Physicians and is Analysis Lead for the National Asthma and COPD Audit Programme.

Professor Nawar Bakerly, consultant respiratory physician for Salford Royal NHS Foundation Trust Professor Nawar Bakerly MD, FRCP is a consultant respiratory physician at Salford Royal NHS Foundation Trust and visiting professor at Manchester Metropolitan University. He is also clinical director for the Department of Respiratory Medicine (Pulmonology) and Chief Clinical Information Officer (CCIO) for Salford Care Organisation – as well as being its lead for integrated COPD services. He has collaborated as lead investigator or co-investigator in clinical trials, including the Salford Lung Studies for asthma and COPD, and also works on various clinical advisory groups for NICE and the NIHR in the UK.

About Savana

savana

Founded in 2014, Savana is an international medical company that has developed a scientific methodology that applies Artificial Intelligence (AI) to unlock all the clinical value embedded within the free-text of Electronic Health Records (EHRs). With the largest AI-enabled, multi-language, multi-centre research network in the world, Savana generates customised descriptive and predictive, Deep Real World Evidence research studies. Savana is built following the highest privacy-by-design standards and with medical reliability engineered by doctors for doctors. Savana constitutes a clinical research ecosystem that aims to advance personalised and precision medicine worldwide.

About BREATHE

BREATHE facilitates the safe and responsible use of respiratory health data at scale, sparking research and innovation for the benefit of UK patients. BREATHE is a collaboration with patients and publics, universities, third sector organisations and industry from across the UK and globally. The Hub is led by The University of Edinburgh, Imperial College London, University of Leicester, Nottingham University Hospitals NHS Trust, Queen Mary University of London and Swansea University. Launched in 2019, BREATHE is one of seven Health Data Research Hubs across the UK. Coordinated by Health Data Research UK, the Hubs are part of a four-year £37.5million investment from UK Research and Innovation’s Industrial Strategy Challenge Fund.

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Red Candle In The Wind

Red Candle In The Wind

By Benjamin PIcton of Rabobank

February non-farm payrolls superficially exceeded market expectations on Friday by…

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Red Candle In The Wind

By Benjamin PIcton of Rabobank

February non-farm payrolls superficially exceeded market expectations on Friday by printing at 275,000 against a consensus call of 200,000. We say superficially, because the downward revisions to prior months totalled 167,000 for December and January, taking the total change in employed persons well below the implied forecast, and helping the unemployment rate to pop two-ticks to 3.9%. The U6 underemployment rate also rose from 7.2% to 7.3%, while average hourly earnings growth fell to 0.2% m-o-m and average weekly hours worked languished at 34.3, equalling pre-pandemic lows.

Undeterred by the devil in the detail, the algos sprang into action once exchanges opened. Market darling NVIDIA hit a new intraday high of $974 before (presumably) the humans took over and sold the stock down more than 10% to close at $875.28. If our suspicions are correct that it was the AIs buying before the humans started selling (no doubt triggering trailing stops on the way down), the irony is not lost on us.

The 1-day chart for NVIDIA now makes for interesting viewing, because the red candle posted on Friday presents quite a strong bearish engulfing signal. Volume traded on the day was almost double the 15-day simple moving average, and similar price action is observable on the 1-day charts for both Intel and AMD. Regular readers will be aware that we have expressed incredulity in the past about the durability the AI thematic melt-up, so it will be interesting to see whether Friday’s sell off is just a profit-taking blip, or a genuine trend reversal.

AI equities aside, this week ought to be important for markets because the BTFP program expires today. That means that the Fed will no longer be loaning cash to the banking system in exchange for collateral pledged at-par. The KBW Regional Banking index has so far taken this in its stride and is trading 30% above the lows established during the mini banking crisis of this time last year, but the Fed’s liquidity facility was effectively an exercise in can-kicking that makes regional banks a sector of the market worth paying attention to in the weeks ahead. Even here in Sydney, regulators are warning of external risks posed to the banking sector from scheduled refinancing of commercial real estate loans following sharp falls in valuations.

Markets are sending signals in other sectors, too. Gold closed at a new record-high of $2178/oz on Friday after trading above $2200/oz briefly. Gold has been going ballistic since the Friday before last, posting gains even on days where 2-year Treasury yields have risen. Gold bugs are buying as real yields fall from the October highs and inflation breakevens creep higher. This is particularly interesting as gold ETFs have been recording net outflows; suggesting that price gains aren’t being driven by a retail pile-in. Are gold buyers now betting on a stagflationary outcome where the Fed cuts without inflation being anchored at the 2% target? The price action around the US CPI release tomorrow ought to be illuminating.

Leaving the day-to-day movements to one side, we are also seeing further signs of structural change at the macro level. The UK budget last week included a provision for the creation of a British ISA. That is, an Individual Savings Account that provides tax breaks to savers who invest their money in the stock of British companies. This follows moves last year to encourage pension funds to head up the risk curve by allocating 5% of their capital to unlisted investments.

As a Hail Mary option for a government cruising toward an electoral drubbing it’s a curious choice, but it’s worth highlighting as cash-strapped governments increasingly see private savings pools as a funding solution for their spending priorities.

Of course, the UK is not alone in making creeping moves towards financial repression. In contrast to announcements today of increased trade liberalisation, Australian Treasurer Jim Chalmers has in the recent past flagged his interest in tapping private pension savings to fund state spending priorities, including defence, public housing and renewable energy projects. Both the UK and Australia appear intent on finding ways to open up the lungs of their economies, but government wants more say in directing private capital flows for state goals.

So, how far is the blurring of the lines between free markets and state planning likely to go? Given the immense and varied budgetary (and security) pressures that governments are facing, could we see a re-up of WWII-era Victory bonds, where private investors are encouraged to do their patriotic duty by directly financing government at negative real rates?

That would really light a fire under the gold market.

Tyler Durden Mon, 03/11/2024 - 19:00

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Trump “Clearly Hasn’t Learned From His COVID-Era Mistakes”, RFK Jr. Says

Trump "Clearly Hasn’t Learned From His COVID-Era Mistakes", RFK Jr. Says

Authored by Jeff Louderback via The Epoch Times (emphasis ours),

President…

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Trump "Clearly Hasn't Learned From His COVID-Era Mistakes", RFK Jr. Says

Authored by Jeff Louderback via The Epoch Times (emphasis ours),

President Joe Biden claimed that COVID vaccines are now helping cancer patients during his State of the Union address on March 7, but it was a response on Truth Social from former President Donald Trump that drew the ire of independent presidential candidate Robert F. Kennedy Jr.

Robert F. Kennedy Jr. holds a voter rally in Grand Rapids, Mich., on Feb. 10, 2024. (Mitch Ranger for The Epoch Times)

During the address, President Biden said: “The pandemic no longer controls our lives. The vaccines that saved us from COVID are now being used to help beat cancer, turning setback into comeback. That’s what America does.”

President Trump wrote: “The Pandemic no longer controls our lives. The VACCINES that saved us from COVID are now being used to help beat cancer—turning setback into comeback. YOU’RE WELCOME JOE. NINE-MONTH APPROVAL TIME VS. 12 YEARS THAT IT WOULD HAVE TAKEN YOU.”

An outspoken critic of President Trump’s COVID response, and the Operation Warp Speed program that escalated the availability of COVID vaccines, Mr. Kennedy said on X, formerly known as Twitter, that “Donald Trump clearly hasn’t learned from his COVID-era mistakes.”

“He fails to recognize how ineffective his warp speed vaccine is as the ninth shot is being recommended to seniors. Even more troubling is the documented harm being caused by the shot to so many innocent children and adults who are suffering myocarditis, pericarditis, and brain inflammation,” Mr. Kennedy remarked.

“This has been confirmed by a CDC-funded study of 99 million people. Instead of bragging about its speedy approval, we should be honestly and transparently debating the abundant evidence that this vaccine may have caused more harm than good.

“I look forward to debating both Trump and Biden on Sept. 16 in San Marcos, Texas.”

Mr. Kennedy announced in April 2023 that he would challenge President Biden for the 2024 Democratic Party presidential nomination before declaring his run as an independent last October, claiming that the Democrat National Committee was “rigging the primary.”

Since the early stages of his campaign, Mr. Kennedy has generated more support than pundits expected from conservatives, moderates, and independents resulting in speculation that he could take votes away from President Trump.

Many Republicans continue to seek a reckoning over the government-imposed pandemic lockdowns and vaccine mandates.

President Trump’s defense of Operation Warp Speed, the program he rolled out in May 2020 to spur the development and distribution of COVID-19 vaccines amid the pandemic, remains a sticking point for some of his supporters.

Vice President Mike Pence (L) and President Donald Trump deliver an update on Operation Warp Speed in the Rose Garden of the White House in Washington on Nov. 13, 2020. (Mandel Ngan/AFP via Getty Images)

Operation Warp Speed featured a partnership between the government, the military, and the private sector, with the government paying for millions of vaccine doses to be produced.

President Trump released a statement in March 2021 saying: “I hope everyone remembers when they’re getting the COVID-19 Vaccine, that if I wasn’t President, you wouldn’t be getting that beautiful ‘shot’ for 5 years, at best, and probably wouldn’t be getting it at all. I hope everyone remembers!”

President Trump said about the COVID-19 vaccine in an interview on Fox News in March 2021: “It works incredibly well. Ninety-five percent, maybe even more than that. I would recommend it, and I would recommend it to a lot of people that don’t want to get it and a lot of those people voted for me, frankly.

“But again, we have our freedoms and we have to live by that and I agree with that also. But it’s a great vaccine, it’s a safe vaccine, and it’s something that works.”

On many occasions, President Trump has said that he is not in favor of vaccine mandates.

An environmental attorney, Mr. Kennedy founded Children’s Health Defense, a nonprofit that aims to end childhood health epidemics by promoting vaccine safeguards, among other initiatives.

Last year, Mr. Kennedy told podcaster Joe Rogan that ivermectin was suppressed by the FDA so that the COVID-19 vaccines could be granted emergency use authorization.

He has criticized Big Pharma, vaccine safety, and government mandates for years.

Since launching his presidential campaign, Mr. Kennedy has made his stances on the COVID-19 vaccines, and vaccines in general, a frequent talking point.

“I would argue that the science is very clear right now that they [vaccines] caused a lot more problems than they averted,” Mr. Kennedy said on Piers Morgan Uncensored last April.

“And if you look at the countries that did not vaccinate, they had the lowest death rates, they had the lowest COVID and infection rates.”

Additional data show a “direct correlation” between excess deaths and high vaccination rates in developed countries, he said.

President Trump and Mr. Kennedy have similar views on topics like protecting the U.S.-Mexico border and ending the Russia-Ukraine war.

COVID-19 is the topic where Mr. Kennedy and President Trump seem to differ the most.

Former President Donald Trump intended to “drain the swamp” when he took office in 2017, but he was “intimidated by bureaucrats” at federal agencies and did not accomplish that objective, Mr. Kennedy said on Feb. 5.

Speaking at a voter rally in Tucson, where he collected signatures to get on the Arizona ballot, the independent presidential candidate said President Trump was “earnest” when he vowed to “drain the swamp,” but it was “business as usual” during his term.

John Bolton, who President Trump appointed as a national security adviser, is “the template for a swamp creature,” Mr. Kennedy said.

Scott Gottlieb, who President Trump named to run the FDA, “was Pfizer’s business partner” and eventually returned to Pfizer, Mr. Kennedy said.

Mr. Kennedy said that President Trump had more lobbyists running federal agencies than any president in U.S. history.

“You can’t reform them when you’ve got the swamp creatures running them, and I’m not going to do that. I’m going to do something different,” Mr. Kennedy said.

During the COVID-19 pandemic, President Trump “did not ask the questions that he should have,” he believes.

President Trump “knew that lockdowns were wrong” and then “agreed to lockdowns,” Mr. Kennedy said.

He also “knew that hydroxychloroquine worked, he said it,” Mr. Kennedy explained, adding that he was eventually “rolled over” by Dr. Anthony Fauci and his advisers.

President Donald Trump greets the crowd before he leaves at the Operation Warp Speed Vaccine Summit in Washington on Dec. 8, 2020. (Tasos Katopodis/Getty Images)

MaryJo Perry, a longtime advocate for vaccine choice and a Trump supporter, thinks votes will be at a premium come Election Day, particularly because the independent and third-party field is becoming more competitive.

Ms. Perry, president of Mississippi Parents for Vaccine Rights, believes advocates for medical freedom could determine who is ultimately president.

She believes that Mr. Kennedy is “pulling votes from Trump” because of the former president’s stance on the vaccines.

“People care about medical freedom. It’s an important issue here in Mississippi, and across the country,” Ms. Perry told The Epoch Times.

“Trump should admit he was wrong about Operation Warp Speed and that COVID vaccines have been dangerous. That would make a difference among people he has offended.”

President Trump won’t lose enough votes to Mr. Kennedy about Operation Warp Speed and COVID vaccines to have a significant impact on the election, Ohio Republican strategist Wes Farno told The Epoch Times.

President Trump won in Ohio by eight percentage points in both 2016 and 2020. The Ohio Republican Party endorsed President Trump for the nomination in 2024.

“The positives of a Trump presidency far outweigh the negatives,” Mr. Farno said. “People are more concerned about their wallet and the economy.

“They are asking themselves if they were better off during President Trump’s term compared to since President Biden took office. The answer to that question is obvious because many Americans are struggling to afford groceries, gas, mortgages, and rent payments.

“America needs President Trump.”

Multiple national polls back Mr. Farno’s view.

As of March 6, the RealClearPolitics average of polls indicates that President Trump has 41.8 percent support in a five-way race that includes President Biden (38.4 percent), Mr. Kennedy (12.7 percent), independent Cornel West (2.6 percent), and Green Party nominee Jill Stein (1.7 percent).

A Pew Research Center study conducted among 10,133 U.S. adults from Feb. 7 to Feb. 11 showed that Democrats and Democrat-leaning independents (42 percent) are more likely than Republicans and GOP-leaning independents (15 percent) to say they have received an updated COVID vaccine.

The poll also reported that just 28 percent of adults say they have received the updated COVID inoculation.

The peer-reviewed multinational study of more than 99 million vaccinated people that Mr. Kennedy referenced in his X post on March 7 was published in the Vaccine journal on Feb. 12.

It aimed to evaluate the risk of 13 adverse events of special interest (AESI) following COVID-19 vaccination. The AESIs spanned three categories—neurological, hematologic (blood), and cardiovascular.

The study reviewed data collected from more than 99 million vaccinated people from eight nations—Argentina, Australia, Canada, Denmark, Finland, France, New Zealand, and Scotland—looking at risks up to 42 days after getting the shots.

Three vaccines—Pfizer and Moderna’s mRNA vaccines as well as AstraZeneca’s viral vector jab—were examined in the study.

Researchers found higher-than-expected cases that they deemed met the threshold to be potential safety signals for multiple AESIs, including for Guillain-Barre syndrome (GBS), cerebral venous sinus thrombosis (CVST), myocarditis, and pericarditis.

A safety signal refers to information that could suggest a potential risk or harm that may be associated with a medical product.

The study identified higher incidences of neurological, cardiovascular, and blood disorder complications than what the researchers expected.

President Trump’s role in Operation Warp Speed, and his continued praise of the COVID vaccine, remains a concern for some voters, including those who still support him.

Krista Cobb is a 40-year-old mother in western Ohio. She voted for President Trump in 2020 and said she would cast her vote for him this November, but she was stunned when she saw his response to President Biden about the COVID-19 vaccine during the State of the Union address.

I love President Trump and support his policies, but at this point, he has to know they [advisers and health officials] lied about the shot,” Ms. Cobb told The Epoch Times.

“If he continues to promote it, especially after all of the hearings they’ve had about it in Congress, the side effects, and cover-ups on Capitol Hill, at what point does he become the same as the people who have lied?” Ms. Cobb added.

“I think he should distance himself from talk about Operation Warp Speed and even admit that he was wrong—that the vaccines have not had the impact he was told they would have. If he did that, people would respect him even more.”

Tyler Durden Mon, 03/11/2024 - 17:00

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There will soon be one million seats on this popular Amtrak route

“More people are taking the train than ever before,” says Amtrak’s Executive Vice President.

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While the size of the United States makes it hard for it to compete with the inter-city train access available in places like Japan and many European countries, Amtrak trains are a very popular transportation option in certain pockets of the country — so much so that the country’s national railway company is expanding its Northeast Corridor by more than one million seats.

Related: This is what it's like to take a 19-hour train from New York to Chicago

Running from Boston all the way south to Washington, D.C., the route is one of the most popular as it passes through the most densely populated part of the country and serves as a commuter train for those who need to go between East Coast cities such as New York and Philadelphia for business.

Veronika Bondarenko captured this photo of New York’s Moynihan Train Hall. 

Veronika Bondarenko

Amtrak launches new routes, promises travelers ‘additional travel options’

Earlier this month, Amtrak announced that it was adding four additional Northeastern routes to its schedule — two more routes between New York’s Penn Station and Union Station in Washington, D.C. on the weekend, a new early-morning weekday route between New York and Philadelphia’s William H. Gray III 30th Street Station and a weekend route between Philadelphia and Boston’s South Station.

More Travel:

According to Amtrak, these additions will increase Northeast Corridor’s service by 20% on the weekdays and 10% on the weekends for a total of one million additional seats when counted by how many will ride the corridor over the year.

“More people are taking the train than ever before and we’re proud to offer our customers additional travel options when they ride with us on the Northeast Regional,” Amtrak Executive Vice President and Chief Commercial Officer Eliot Hamlisch said in a statement on the new routes. “The Northeast Regional gets you where you want to go comfortably, conveniently and sustainably as you breeze past traffic on I-95 for a more enjoyable travel experience.”

Here are some of the other Amtrak changes you can expect to see

Amtrak also said that, in the 2023 financial year, the Northeast Corridor had nearly 9.2 million riders — 8% more than it had pre-pandemic and a 29% increase from 2022. The higher demand, particularly during both off-peak hours and the time when many business travelers use to get to work, is pushing Amtrak to invest into this corridor in particular.

To reach more customers, Amtrak has also made several changes to both its routes and pricing system. In the fall of 2023, it introduced a type of new “Night Owl Fare” — if traveling during very late or very early hours, one can go between cities like New York and Philadelphia or Philadelphia and Washington. D.C. for $5 to $15.

As travel on the same routes during peak hours can reach as much as $300, this was a deliberate move to reach those who have the flexibility of time and might have otherwise preferred more affordable methods of transportation such as the bus. After seeing strong uptake, Amtrak added this type of fare to more Boston routes.

The largest distances, such as the ones between Boston and New York or New York and Washington, are available at the lowest rate for $20.

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