Category Archives: Alternative Medicine

Many in Thailand had initially opposed the introduction of medical marijuana but solid science is slowly changing perceptions, say doctors Krit Pongpirul and Sornkanok Vimolmangkang.

PETALING JAYA: A total of 406 cancer patients, 257 migraine patients, 135 Parkinsons patients and 3,337 people experiencing body aches felt less pain, slept well, and ate better after a month-long experiment.

The patients had received their treatment as part of a research project led by Dr Krit Pongpirul, a member of the Faculty of Medicine at Thailands prestigious Chulalongkorn University.

The treatment? A drop of cannabis oil.

Krit says the findings of the study involving some 20,000 patients from 30 hospitals throughout Thailand are promising.

His colleague Sornkanok Vimolmangkang, from the universitys Faculty of Pharmaceutical Sciences, says this is something Malaysia can consider looking into.

The use of cannabis in medical treatments has been a contentious issue in Malaysia, which has some of the most punitive drug policies in the world.

Recently, an engineer who sold cannabis oil to treat cancer patients came close to the gallows until the Federal Court spared him by allowing his appeal on two counts of trafficking. He was still sentenced to five years in jail for possession, though.

In an interview with FMT, both Krit and Sornkanok said many in Thailand had initially opposed the introduction of medical marijuana but solid science is slowly changing perceptions.

Its not all bad nor magic either

Krit, who is trained in conventional medicine and health services research, says one of the main challenges facing medical marijuana is the extreme and vague narratives of both its supporters and detractors.

For one, when we talk about medical marijuana, there are too many products with unclear evidence on disease-specific clinical outcomes, so the detractors assume it is bad because they do not know what researchers are talking about exactly. They think it will lead to other issues.

On the other hand, those who support medical marijuana make all sorts of claims about it as if it is magic, and this leads to doubt among conventional medical practitioners.

He said this is why he decided on a very specific product and systematic approach for his research.

The doctors formulated a cannabis oil which has very low amounts of tetrahydrocannabinol (THC) and cannabidiol (CBD), which are psychoactive compounds. This ganja oil was approved by the Thai Ministry of Public Healths Department of Thai Traditional and Alternative Medicine (DTAM) and Food and Drug Administration (FDA) for research purposes.

As for what the research aimed to determine, Krit said it focused on not only how the oil helped improve quality of life and also the medical benefits it could have but also how the traditional and conventional medicine doctors prescribe the oil in real clinical settings.

We were not trying to prove any claims that it cures cancer or anything of the sort.

Each patient was prescribed a bottle of cannabis oil and was reassessed biweekly during the course of three months, with the patients being able to adjust how many drops of oil they would consume a day.

The patients would have to fill two globally recognised questionnaires to track the effectiveness of the oil in improving their quality of life the Edmonton Symptom Assessment Scale (ESAS) and EQ-5D.

After a month of trials, Krit says many who took just one drop of cannabis oil a day found significant improvements in their quality of life with minimal side effects.

The preliminary findings were presented at the American Public Health Associations 2020 annual meeting and expo in San Francisco.

He said the findings of the second and third month of trials will be published by the Thai Public Health Ministry soon, though the authorities have approved its use for treating pain, insomnia and anorexia in the National List of Herbal Medicine and included in the benefits package under the Universal Coverage scheme to be financially subsidised by the National Health Security Office (NHSO).

It is only distributed through government hospitals.

Of course, we need more studies, on the other health benefits, how it can be used to treat specific diseases and how cannabis compares with conventional medicine, he said.

Sornkanok said while there was a lot of opposition against exploring medical marijuana in Thailand, they are seeing attitudes change.

The research suggests it can bring more good than harm. If it can help people, why not? We just need to change mindsets and perceptions through solid science, and the first step is to be open to research.

Read this article:

Ganja oil, and the science behind changing views in Thailand - Free Malaysia Today

Cultural adaptations likely improve the effectiveness of psychological interventions for sleep disorders. These findings, from a systematic review, were published in Sleep Medicine Reviews.

Researchers from Columbia University searched publication databases for randomized clinical trials of psychological interventions for sleep disorders conducted in the United States. A total of 56 studies were included in the final analysis.

These studies comprised an average sample size of 85.23 (range, 11-219) individuals in the intervention and 38.40 (range, 5-91) individuals in the control arms. The vast majority had 2-arm trial designs (91.07%) lasting an average of 7.69 weeks (range, 2 weeks to 2 years).

These studies were dominated by participants who were women (mean, 55.35%; standard deviation [SD], 43.22%) and White (mean, 64.86%; SD, 21.67%) and only 6.97% focused on underserved populations.

Participants had definitive diagnoses of a sleep disorder in 32 studies, 9 studies included individuals with probable sleep disturbance, and 15 with potential sleep disturbance. Among studies of patients with an established diagnosis, 75% studied insomnia, 9.38% nightmares with poor sleep quality, 6.25% poor sleep quality, 3.12% restless leg syndrome, 3.12% nocturia, and 3.12% nightmares with insomnia.

The primary outcome was sleep quality (n=40), insomnia (n=30), sleep efficiency (n=21), sleep duration (n=21), nightmares (n=8), and drowsiness (n=4).

The most studied interventions were cognitive behavioral therapy for insomnia (CBT-I; n=20), complementary and alternative medicine (n=8), and behavioral therapy (n=7), cognitive behavioral therapy (n=4), among others.

These interventions were tailored to their study populations by either surface- and/or deep-level cultural adaptations (64.29%). CBT-I was most commonly adapted (38.89%). Surface-level adaptations included changes to the delivery modality, setting, dosing, constituent-involving strategies, and linguistic changes. Deep-level adaptations were content-level, core component, sociocultural, and linguistic changes.

The studies with a cultural adaptation component generally found insomnia was significantly improved compared with pharmacotherapy, but few found changes in nightmares, sleep efficiency, or sleep duration.

Participants who received CBT-I with surface- or deep-level cultural adaptation (n=11 studies) had significantly improved symptoms of insomnia compared with various control groups, usual care, hygiene education, or healthy eating educations. A subset of these studies also reported improvements to sleep efficiency (n=6) and sleep quality (n=7).

Few studies of surface- or deep-level cultural adaptations for interventions of probable or possible sleep disturbances found significant improvements to sleep.

These findings were limited by the underlying study populations which lacked diversity.

The study authors concluded that interventions for established sleep disorders which have been culturally tailored for the population were more successful than control conditions or usual care.

Reference

Alcntara C, Cosenzo LG, McCullough E, Vogt T, Falzon AL, Ibarra IP. Cultural adaptations of psychological interventions for prevalent sleep disorders and sleep disturbances: A systematic review of randomized controlled trials in the United States. Sleep Med Rev. 2021;101455. doi:10.1016/j.smrv.2021.101455

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Psychological Interventions With Cultural Adaptations More Effective for Treatment of Sleep Disorders - Psychiatry Advisor

During the tumultuous weeks and months of the past year, a nine-letter word emerged as a game changer for the nations legal marijuana industry: essential.

It began about a week after the World Health Organization on March 11 declared the COVID-19 outbreak a global pandemic.

Thats when California announced a statewide business lockdown, followed by Illinois.

Both states also designated marijuana operators as essential along with pharmacies, supermarkets and liquor stores and those businesses were allowed to stay open.

California and Illinois were soon followed by dozens of other states that declared marijuana operators as essential businesses.

In all, nearly 30 states with functional marijuana markets as well as the District of Columbia and Puerto Rico deemed marijuana businesses as essential.

The rush of essential designations in the early weeks of the pandemic proved to be one of the most momentous moments in the timeline of the nations legal marijuana industry and it arguably helped lead to the creation of new state-legal MJ markets that are projected to generate billions of dollars in sales.

By casting marijuana as essential, states put the cannabis industry in the same category as pharmacies, hospitals and other sources of legitimate medicine.

In short, cannabis went from an alternative treatment to an essential medicine, giving it a major upgrade in credibility.State regulators and health experts sanctioned that upgrade.

Moreover, states put marijuana on the same footing as a federally legal industry, alcohol.

The hope was that with the essential designation, there would be more recognition that cannabis was here to stay, that there was strong consumer preference for it, said Steve Hawkins, executive director of the Washington DC-based Marijuana Policy Project and CEO of the U.S. Cannabis Council.

I think thats been borne out by the amount of usage over this pandemic period.

Liesl Bernard, CEO of Cannabiz Team, a marijuana-focused recruitment firm in San Diego, agreed.

The fact that you couldnt go to your hairdresser but you could go to a dispensary opened a lot of peoples eyes that this is an industry thats here to stay, Bernard said.

She added that the essential designation has spurred greater interest among professionals for working in the cannabis industry, especially at a time when many of those professionals have lost jobs in other industries.

They see that its essential, they see retail sales are up, and so they see that its going to be the next big industry, Bernard said.

The essential designation triggered other major changes in the marijuana industry:

These factors helped state-legal marijuana markets across the country break sales records in 2020.

Industry observers also say the essential designation spurred marijuana legalization in seven states five by ballot initiative and two by legislatures. It also increased momentum at the federal level for reform.

But entrepreneurs and advocates have also found that the essential designation has had limitations.

For all the positive change with consumers and revenue-starved state officials, serious obstacles remain lack of banking access, federal prohibition and medical-establishment skepticism, among others.

In short, the essential designation hasnt swayed all those who have the authority to undo those obstacles.

By the numbers

According to a Marijuana Policy Project analysis of legal marijuana markets in 32 states and Washington DC, all except one Massachusetts recreational market were allowed to stay open during state-mandated stay-at-home orders.

Massachusetts medical market was declared essential and continued operating, while the recreational market was allowed to resume sales on May 25.

Of those 33 markets, 28 explicitly declared marijuana businesses as essential (including Massachusetts MMJ market), and three states had lockdowns but allowed cannabis businesses to continue operating without explicitly designating them as essential, according to the MPP.

Arkansas and North Dakota didnt implement statewide lockdowns, so the essential designation was moot.

Iowa instituted lockdowns in some areas but still made a distinction between essential and non-essential businesses, with cannabis companies designated as essential.

Of those 33 markets, 18 allowed home delivery of marijuana before COVID-19, five added delivery in response to the pandemic and 10 did not make delivery an option, according to the MPP.

Of those 33 markets, 10 allowed curbside and/or drive-thru pickup before the pandemic, and 19 allowed curbside and/or drive-thru service in response. In four states, curbside or drive-thru pickup were not options.

And of those 33 markets:

Credibility with consumers

The essential designation had the most sway with consumers, as evidenced by the sales surge that cannabis has experienced during the pandemic.

People finally recognize this for what it is. Its medicine, said Gary Santo, CEO of Tilt Holdings, a multistate operator headquartered in Phoenix that also owns a major vaporizer manufacturer, Jupiter Research.

You can look at the demographics and see how many people are approaching the plant with something in mind; with joint pain, anxiety, with trying to manage a condition. And I think it became really clear, especially during the pandemic, how important this was. People look at it now a little bit more like a medicine.

Referencing a marijuana legalization bill passed in the U.S. House of Representatives last year, the MPPs Hawkins said: The essential designation helped to legitimize cannabis as an important part of not only state economies but also incredibly important to patients and to recreational consumers.

And that background certainly helped to define the efforts that we saw last year, with the MORE Act passing in Congress.

Help at the state and federal levels

Hawkins and other observers say the essential designation was a factor last November when voters in five states legalized recreational and medical marijuana markets through ballot initiatives.

Together, those states could generate more than $2.5 billion in annual medical and recreational cannabis sales by 2024.

Separately, lawmakers in Vermont approved a recreational marijuana program last October. That program is projected to generate roughly $250 millionin annual sales by 2025.

Virginia legislators followed suit last month, approving an adult-use program that could generate nearly $1.5 billion in annual sales within five years of the scheduled Jan. 1, 2024, start.

At the federal level, the essential designation has helped move the needle on marijuana reform.

Throughout the presidential debates, at least on the Democratic side, there was very robust discussion around cannabis legalization, Hawkins noted.That didnt happen in a vacuum.

It underscored that, in the middle of a pandemic, cannabis was being deemed an essential commodity. And that was reflected in the fact that every presidential candidate had something to say about cannabis, with most believing that it should be legalized.

While the essential designation was persuasive with consumers, state regulators and some members of Congress, it so far has failed to persuade federal officials to end the governments marijuana prohibition.

The essential designation has yet to spur congressional passage of more moderate steps, including:

The essential designation also failed to change the mind of major medical institutions.

In December, the American Medical Association sent a letter to House Speaker Nancy Pelosi arguing against the MORE Act, although the physicians group did support bills that would allow for more medical research of cannabis.

There was always a bit of a disappointment for me, because if youre deemed essential, and yet youre not able to qualify for things that others in that category can qualify for, it made it a little bit of a dichotomy in terms of common sense, said Geoff Bacino, a former federal banking regulator and now a Washington DC-based consultant whose clients include marijuana businesses.

While the essential designation has made it easier for state politicians to argue for legalization or liberalizing regulations, Bacino is less certain its changed any minds in Congress.

It might help them feel a little less reticent, but on the whole, I find that most members, especially those that have been around for the last couple of sessions of Congress, are pretty set in their ways, Bacino said.

The question is, can you just get a bill on the floor that causes people to vote? Im not sure that designation is going to change anybodys mind, but it may make somebody feel a little more comfortable with their decision.

Omar Sacirbey can be reached at[emailprotected].

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How essential transformed the US marijuana industry amid the COVID-19 pandemic - Marijuana Business Daily

The main street of Mullumbimby.(

ABC News: Bridget Judd

Mullumbimby has long been defined by its "live and let live" ethos. But for those left to grapple with the reality of lagging vaccination rates, this isn't a game of semantics it's life and death.

Take a trip to the Brunswick Valley, where the tiny town of Mullumbimby sits under the shadows of Mount Chincogan, and there's one topic that's met with a pause.

"Around here, vaccines are like politics or religion," says local Heidi Robertson.

"You just don't bring it up in conversation."

With childhood immunisation rates in northern New South Wales among the lowest in the country, this reticence is unsurprising.

ABC News: Bridget Judd

A hotbed for alternative medicine, the laidback community has long been defined by its "live and let live" ethos and with it, comes a familiar phrase.

"We're not anti-vaxx, we're just pro-choice."

But for those left to grapple with the reality of lagging vaccination rates, it isn't a game of semantics: it is, quite literally, life or death.

And they're determined to change the narrative.

"You mention to anyone Byron Bay, Mullumbimby or Nimbin, and the first thing that pops into their mind is the hippie culture," says Robertson from the Northern Rivers Vaccination Supporters, a grassroots group of parents, locals and healthcare providers trying to improve vaccination rates.

"And if you move here looking for that alternative lifestyle, being anti-vaccination is a part of that."

ABC News: Bridget Judd

Surrounded by dense farmland that gives way to sweeping views of the hinterland, the former timber town is far more nuanced than its banal stereotypes would suggest.

Amidst frustration with Australia's involvement in the Vietnam War, "draft dodgers", university students and 20-somethings who had tired of "the rat race" migrated to the region in the late 60s and early 70s, says local filmmaker, Sharon Shostak.

Brunswick Valley Historical Society/Sharon Stozak: Mullumbimby's Madness

Brunswick Valley Historical Society/Sharon Stozak: Mullumbimby's Madness

Brunswick Valley Historical Society/Sharon Shostak: Mullumbimby's Madness

Even before this, the region had experienced waves of settlement: first farmers, then "a wave of Chinese settlers, a wave of Italians", says Shostak, who documented the history of the town in her three-part series, Mullumbimby's Madness.

"Each time there was this wave of settlers coming through the town. So we're kind of used to weird, different, unusual, and are very accepting, there was this tradition of just integrating quite easily."

Now an eclectic mix of wellness stores, organics and small business, there is a communal sense of responsibility that underpins Mullumbimby: to the environment, to sustainability, and to one another.

But walk through the centre of town, and you'll come to understand why its reputation as a hippy-holdout just won't budge.

ABC News: Bridget Judd

By the local supermarket, a barefoot busker breaks from the group, retreating down an alleyway to light a joint. Nearby, people filter in and out of a crystal sanctuary and herbal dispensary offering naturopathic medicines and consultations.

And there, above a bespoke retail store on the town's main street, is a banner that hardly draws a second glance.

"NO FORCED INJECTIONS," it reads. "MY BODY MY CHOICE."

Step off the main street and into the GP's office, and you get a different story.

It's a sight Dr Chris Ingall will never forget. A four-week-old baby, bleeding from the mouth and nose.

"It's an awful, awful sight for a little bub like that," he says softly.

"Cerebral, pulmonary, bowel just haemorrhaging."

ABC News: Bridget Judd

It was 2010, and Ingall a paediatrician in nearby Lismore knew immediately the child was suffering from vitamin K deficiency bleeding (VKDB), a potentially life-threatening ailment in infants up to six months of age.

The natural deficiency killed more than a dozen babies per year in NSW in the late 1960s and early 70s, before vitamin K injections were widely adopted.

"This mum had been told by a healthcare provider, who was actually on the state payroll in Byron, the vitamin K was a 'vaccine', and that it was not necessary," Ingall says.

"I tried to explain to her at the time the baby's coagulation profile was that of a child who was in need of vitamin K. But it was too late. They'd passed away."

"She did not want to face the fact that it was connected."

ABC News: Bridget Judd

ABC News: Bridget Judd

Though a harrowing scenario, it is not unprecedented.

Research into incidents of VKDB in Australian infants between 1993 and 2017, published in the BMJ, found the number of recorded cases following parental refusals "doubled in the second half of the study and further increased in the last five years" of it.

Of the 14 cases of VKDB reported between 2013 and 2017, 71 per cent (10) did not receive vitamin K because their parents refused consent.

The study found 39 per cent of cases following parental refusal occurred in northern NSW and south-east Queensland, "areas where immunisation refusal rates are highest in Australia".

"The [baby] could have had a great life," Ingall says. "But they were denied that, just through a piece of information, which was wrong and believed."

For most, it is an unfathomable contradiction.

How can someone want what is best for their child, while simultaneously rejecting the medical advice that could save their life?

It's "not a deficit in knowledge that's the problem", Robertson says.

"Your level of education or level of intelligence makes no difference," she says. "It's far more complicated than that."

Source: NSW Health

Across the Byron shire, which takes in Mullumbimby, just 63.6 per cent of children aged two were fully immunised as of June last year significantly below the state average of 91.4 per cent.

At five years, that figure increases to 73.9 per cent (compared to the state average of 94.2 per cent). But for those frustrated by the region's vaccination rates, these aren't just numbers they're decisions that carry real and sometimes fatal consequences for those most vulnerable.

During a whooping cough outbreak that swept through NSW in 2009, a four-week-old baby girl lost her life.

In the same week she passed away in Lismore Base Hospital, two other babies had to be airlifted to Brisbane for emergency treatment.

Robertson says the family of the baby who died "were absolutely slammed and vilified on social media by anti-vaccination people who said they were lying about their baby having even had whooping cough".

"Some people said 'your baby didn't even exist'."

While a scepticism to vaccines was almost the "default clause" when Ingall first moved to the region in the 1980s, he believes anti-vaccination campaigners were galvanised by global controversy over the pertussis whole-cell vaccines, which were used to prevent whooping cough before being phased out in Australia a decade later in favour of the acellular vaccine.

And on that, he is candid: "We gave them a platform".

At the turn of the 1980s, global confidence in the whole-cell vaccine had begun to wane. Reports had emerged from the United Kingdom about alleged neurological reactions, while concerns over the use of whole-cell vaccines in the United States led to lawsuits against vaccine manufacturers, pushing up prices and prompting some companies to cease production.

Back home, side-effects like fever and irritability had been reported in children, but some within the community felt "marginalised and silenced" by doctors, says Ingall, creating "a situation where people no longer trusted it".

Confused about Australia's vaccine rollout? We've tracked down the answers to the questions you've been asking.

During a debate at the town hall in the late 1980s, he recalls a "visceral howl" from the audience when a doctor took to the stage to try to calm their concerns.

"They'd taken their children along for vaccination, they'd had these reactions, and they've been told, 'Oh no, it's just a cold', or 'it's just this' or 'just that'," he says.

"And we've got to be really open about that, because these events will come up again.

"We gave them a platform, a platform that they had been marginalised and silenced."

Trust, or rather, a lack thereof: it's a familiar theme that emerges in Mullumbimby's relationship with mainstream medicine.

As the region's reputation as a counter-culture hub was beginning to take hold in the 70s, Shostak notes, a natural "evolution of wellness" was emerging.

Brunswick Valley Historical Society/Sharon Stozak: Mullumbimby's Madness

"People weren't just willing to accept what they were given or what they were told to do," she says.

Brunswick Valley Historical Society/Sharon Stozak: Mullumbimby's Madness

"I think a big, big factor in the settlement was people looking for alternatives."

In what some view asan inexorable legacy of thecommunity's early search forhealth and wellbeing, the useof naturopaths and homeopaths asprimary healthcare providers isnot unusual.

Scan the health notices inthe local paper, Shostak says, and "it's just like an encyclopedia of alternative therapies" something she sees as a positive that has"given people a chance toexperiment".

But Robertson is concerned bytheir level of influence. "They are big swayer ofopinion in this region,"she says.

"The naturopaths and homeopathsand the chiropractors, [some will say] they cankeep your immune system healthyand you don't need vaccinations," she says.

Source: NSW Health

"We've even got homeopaths here selling 'alternatives to vaccination' under the counter. It's against the law to do that ... But everyone knows that they do."

According to the National Centre for Immunisation Research and Surveillance, the Australian Homoeopathic Association has "strict guidelines in place regarding the use of homoeopathic 'immunisation'".

That includes a "compulsory consent form stating the treatment is not an immunisation, that no prophylactic treatment guarantees immunity from infectious disease, and that the evidence for the efficacy of homoeopathic 'immunisation' is limited".

Asked about its policy on immunisations and how it's enforced, AHA president Gerry Dendrinos said homeopathic prophylaxis was "not a substitute for vaccinations", adding that practitioners are "not allowed to advise on vaccination and certainly not allowed to dissuade people".

"Practitioners that do that are in breach of the code of conduct, and we do have a compliance pathway where those complaints in the public are dealt with, where we can look at practitioners who have exceeded the scope of practice."

When it comes to tackling misinformation around vaccines, Ingall is candid: "It's a bit like Scott Morrison presenting at a Labor lunch".

"He might have the absolute best logic and reasoning behind what he's saying, but he's not going to sway too many true believers."

With the coronavirus vaccine rollout beginning, those on the frontline are acutely aware of the challenges they face in the region.

In an alcove beside the building where an anti-vaccination banner hangs, a man who identifies himself as David mills by a microphone stand, his guitar case lined with flyers about vaccines and 5G.

ABC News: Bridget Judd

"They want to make more money," he says of the vaccine. "If it's mandatory, then more people get the vax."

The federal government has been clear that the vaccine will not be mandatory and Robertson says there are some who simply "will not get it under any circumstances because they're completely anti-vaccination".

But she points to another growing demographic: the "maybes" or "fence sitters", who are hesitant about getting such a new vaccine.

This reticence is not limited to the coronavirus rollout. Across the wider vaccination divide, Robertson says, "I hear, 'I'm not so much anti-vaccination, but I just can't get past giving my baby a whole bunch of vaccinations'".

It's groups like these that her network hope to reach by "listening to what their concerns are, and then addressing them", one cup of tea at a time.

"It doesn't happen in one conversation," she says. "We have the '1,000 cups of tea' approach, because you just can't expect it to [happen immediately]."

ABC News: Bridget Judd

ABC News: Bridget Judd

ABC News: Bridget Judd

Alongside a team of doctors from across the region, Ingall is determined to do his part to change the narrative around vaccinations.

Having witnessed the needless death of young children, he doesn't mince words: "I will say to [parents], I have watched babies die. I don't want your baby to be one of those babies'."

"These things happen. Join the dots," he says.

"This is real, and what you're being told is not as real as this."

Words and photography: Bridget Judd

Read more here:

Mullumbimby is known as the anti-vaccination capital, but a group of locals is changing the narrative - ABC News

DURHAM, N.C., March 11, 2021 (GLOBE NEWSWIRE) -- Bioventus Inc. (Nasdaq: BVS) (Bioventus or the Company), a leader in solutions for innovative healing, reported that the first patients have been enrolled and dosed in its Phase 1 open-label, dose-escalation study of MOTYS (PTP-001) with Dr. Shailesh Patel, M.D. at Coastal Carolina Research Center, South Carolina. MOTYS is a placental tissue particulate comprised of amnion, chorion and umbilical cord tissue from full-term, healthy births and is provided sterile in micronized form.

The study is evaluating the safety and efficacy of MOTYS (PTP-001) to treat osteoarthritis (OA) of the knee. Researchers are enrolling 20 patients with each patient receiving a single injection of PTP-001.Patients will be followed up to evaluate local and systemic reactions to the drug candidate, as well as to assess any improvements in pain and mobility over the course of this clinical study.

Current treatments for knee OA are limited to corticosteroids and hyaluronic acid (HA) injections. Other options to manage pain, like opioids, are associated with high risks. Bioventus is one of several market leaders in HA therapy used to treat osteoarthritis knee pain with the largest portfolio of HA products including DUROLANE, GELSYN-3 and SUPARTZ FX and believes products such as PTP-001, fill a need and provide more options for physicians and patients in an osteoarthritis market that is growing in scope with the aging population.

The announcement that the first patients have been enrolled and dosed in this Phase 1 clinical study of PTP-001 is an important milestone for Bioventus especially given the challenging environment many clinical research centers are navigating due to COVID-19, said Alessandra Pavesio, Senior Vice President and Chief Science Officer, Bioventus. This trial represents the first of multiple studies that Bioventus intends to conduct to demonstrate the safety and efficacy of our innovative biologic drug candidate designed to treat a prevalent, growing and debilitating condition like knee osteoarthritis, which significantly affects the quality of life of more than 14 million Americans.

About BioventusBioventus delivers clinically proven, cost-effective products that help people heal quickly and safely. Its mission is to make a difference by helping patients resume and enjoy active lives. The Innovations for Active Healing from Bioventus include offerings for osteoarthritis, surgical and non-surgical bone healing. Built on a commitment to high quality standards, evidence-based medicine and strong ethical behavior, Bioventus is a trusted partner for physicians worldwide. For more information, visit http://www.bioventus.com and follow the Company on LinkedIn and Twitter.

Bioventus, the Bioventus logo and DUROLANE are registered trademarks and Bioventus, MOTYS and GELSYN-3 are trademarks of Bioventus LLC. SUPARTZ FX is a trademark of Seikagaku Corp.

Summary of Indications for Use: DUROLANE is indicated for the treatment of pain in osteoarthritis of the knee in patients who have failed to respond adequately to conservative non-pharmacological therapy or simple analgesics, e.g. acetaminophen. Do not inject DUROLANE in patients with knee joint infections, skin diseases, or other infections in the area of the injection site. Do not administer to patients with known hypersensitivity or allergy to sodium hyaluronate preparations. Risks can include transient pain or swelling at the injection site. DUROLANE has not been tested in pregnant or lactating women, or children. Full prescribing information can be found in package insert, at DUROLANE.com, or by contacting Bioventus Customer Service at 1-800-836-4080.

GELSYN-3 is indicated for the treatment of pain in osteoarthritis of the knee in patients who have failed to respond adequately to conservative non-pharmacologic therapy and simple analgesics (e.g. acetaminophen). Do not administer to patients with known hypersensitivity (allergy) to sodium hyaluronate preparations. Do not inject GELSYN-3 into the knees of patients having knee joint infections or skin diseases or infections in the area of the injection site. GELSYN-3 is not approved for pregnant or nursing women, or children. Risks can include general knee pain, warmth and redness or pain at the injection site. Full prescribing information can be found in product labeling, at http://www.GELSYN3.comor by contacting customer service at 1-800-836-4080.

SUPARTZ FX is indicated for treatment of pain in osteoarthritis (osteoarthritis) of the knee in patients who have failed to respond adequately to conservative non-pharmacologic therapy and simple analgesics, e.g., acetaminophen. You should not use SUPARTZ FX if you have infections or skin diseases at the injection site or allergies avian (bird) products (feathers and eggs). SUPARTZ FX is not approved for pregnant or nursing women, or children. Risks can include general knee pain, warmth and redness or pain at the injection site. Full prescribing information can be found in product labeling, at http://www.SupartzFX.com or by contacting customer service at 1-800-836-4080.

Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements concerning the MOTYS (PTP-001) study and additional intended studies, expectations regarding the safety and efficacy of our biologic drug candidate and the results and impact of Bioventus products. In some cases, you can identify forward-looking statements by terminology such as aim, anticipate, assume, believe, contemplate, continue, could, due, estimate, expect, goal, intend, may, objective, plan, predict, potential, positioned, seek, should, target, will, would and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Factors that could cause actual results to differ materially from those contemplated in this press release include, but are not limited to, statements about the adverse impacts on our business as a result of the COVID-19 pandemic; our dependence on a limited number of products; our ability to develop, acquire and commercialize new products, line extensions or expanded indications; the continued and future acceptance of our existing portfolio of products and any new products, line extensions or expanded indications by physicians, patients, third-party payers and others in the medical community; our ability to differentiate the hyaluronic acid (HA) viscosupplementation therapies we own or distribute from alternative therapies for the treatment of osteoarthritic; the proposed down-classification of non-invasive bone growth stimulators, including our Exogen system, by the FDA; our ability to achieve and maintain adequate levels of coverage and/or reimbursement for our products, the procedures using our products, or any future products we may seek to commercialize; our ability to complete acquisitions or successfully integrate new businesses, products or technologies in a cost-effective and non-disruptive manner; competition against other companies; the negative impact on our ability to market our HA products due to the reclassification of HA products from medical devices to drugs in the United States by the FDA; our ability to attract, retain and motivate our senior management and qualified personnel; our ability to continue to research, develop and manufacture our products if our facilities are damaged or become inoperable; failure to comply with the extensive government regulations related to our products and operations; enforcement actions if we engage in improper claims submission practices or in improper marketing or promotion of our products; the FDA regulatory process and our ability to obtain and maintain required regulatory clearances and approvals; failure to comply with the government regulations that apply to our human cells, tissues and cellular or tissue-based products; the clinical studies of any of our future products that do not product results necessary to support regulatory clearance or approval in the United States or elsewhere; and the other risks identified in the Risk Factors section of the Companys public filings with the Securities and Exchange Commission (SEC), including Bioventus 424(b)(4) prospectus filed on February 12, 2021 in connection with the Companys initial public offering, as such factors may be updated from time to time in Bioventus other filings with the SEC, which are accessible on the SECs website atwww.sec.govand the Investor Relations page of Bioventus website atir.bioventus.com. Except to the extent required by law, the Company undertakes no obligation to update or review any estimate, projection, or forward-looking statement. Actual results may differ materially from those set forth in the forward-looking statements.

Media Contact:Thomas Hill919-474-6715thomas.hill@bioventus.com

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Bioventus Reports First Patients Enrolled in Phase 1 Clinical Trial of MOTYS (PTP-001) for the Treatment of Knee OA - BioSpace

Introduction

Idiopathic scoliosis (IS) is the most common form of structural spine deformity in pediatric patients, with reported prevalence estimates ranging between 0.475.2% of children.13 Pediatric patients with IS present with chest deformities and shoulder or waist asymmetry and may experience pain.46 Curves with Cobb angles of greater than 50 at skeletal maturity result in lasting deformity, impaired pulmonary function and reduced health-related quality of life (HRQoL) if left untreated.7,8 Despite this, there are limited definitive treatment options available for patients who are skeletally immature other than bracing or spinal fusion.9

When bracing has failed, or if the spinal curve is rapidly progressing, surgical treatment is usually recommended for Cobb angles greater than 4550 to prevent subsequent progression.7,10,11 The goal of surgical intervention is to correct the deformity and stabilize the spinal curve to prevent further curve progression; with spinal fusion, this is typically achieved with posterior instrumentation with rods anchored to the spine with pedicle screws (Figure 1A).5,12 Spinal fusion results in decreased spinal mobility and range of motion over the instrumented levels, with loss of motion increasing with each additional lower instrumented vertebra in pediatric patients with IS.1316 There is a need for an intervention that can correct spinal curvature deformities in pediatric patients aged >10 years, while allowing for continued growth and preserved range of motion. Several growth-friendly devices are available, such as the growth guidance system (GGS), magnetically controlled growing rods (MCGR) and traditional growing rods (TGR). However, the use of these technologies in recent studies has been limited to younger patient populations,1731 with current indications in the US limited to patients with early-onset scoliosis (<10 years of age),32,33 and while these technologies allow fusion to be delayed until skeletal maturity is reached, a final fusion procedure is still required.

Figure 1 Examples of pediatric patients with idiopathic scoliosis before and 2-years after surgical intervention with (A) spinal fusion or (B) VBT. (A) 15-year-old patient with 55 right thoracic curve treated with spinal fusion at 2 years postoperative follow-up. (B) 15-year-old patient with 55 right thoracic curve treated with anterior vertebral body tethering at 2 years postoperative follow-up.

Abbreviation: VBT, anterior vertebral body tethering.

Anterior vertebral body tethering (VBT) is a non-fusion, minimally invasive growth-modulating procedure that can provide treatment without the need for fusion (Figure 1B); early reports of the clinical efficacy and safety of VBT indicate some positive outcomes for skeletally immature patients aged >10 years with IS.3438 Spinal tethering offers an alternative treatment to spinal fusion for pediatric patients aged >10 years with IS where significant continued growth is expected. Compared with spinal fusion, VBT may minimize the impact on growth while offering improved range of motion and faster return to normal activities.14 Of note, the mechanism of action of VBT relies on continued spinal growth, thus, current indications are limited to skeletally immature patients.34,39

While costs associated with spinal fusion as a treatment for pediatric patients with IS have been reported in the literature, few cost-effectiveness analyses investigating spinal fusion in IS have been performed.4043 Additionally, to the best of our knowledge, there are no previous costing or cost-effectiveness analyses investigating VBT for the treatment of IS. VBT is associated with higher device costs compared with spinal fusion.4447 However, given that VBT may provide benefits in terms of improved range of motion and faster return to normal activities, which may lead to gains in HRQoL for patients who receive VBT as compared with spinal fusion, there is a need for studies investigating the cost-effectiveness of these two procedures.

The objective of this research was to perform a cost-utility analysis (CUA) of spinal tethering as compared with spinal fusion to estimate the incremental differences in costs and utilities in terms of quality-adjusted life-years (QALYs) associated with treating pediatric patients with IS. Our hypothesis is that, over time, utility gains associated with spinal tethering as compared with spinal fusion would sufficiently offset the initial higher cost of the procedure to consider the technology a cost-effective use of healthcare resources from the perspective of an integrated US health care delivery system.

The Consolidated Health Economics Evaluation Reporting Standards (CHEERS) statement was followed for reporting the findings of this analysis.48

The aim of the analysis was to investigate whether VBT is cost-effective as a first-choice surgical treatment option for pediatric patients with moderate to severe IS who have failed nonoperative management, from a US perspective. To address this decision problem, a CUA was undertaken to compare VBT to spinal fusion from the perspective of the US integrated healthcare delivery system (IDS). A CUA is appropriate since differences in both costs and HRQoL may be expected between VBT and spinal fusion.

A willingness-to-pay threshold (WTP) of $100,000 was chosen, corresponding to the lower end of the range ($100,000$150,000) used by the Institute for Clinical and Economic Review in presenting health-benefit price benchmarks, and in line with WHO-CHOICE guidelines (advocating for thresholds of 23 times the gross domestic product per capita).49,50

The patient population chosen for the CUA are those represented by the current FDA indications for VBT which include skeletally immature patients (age >10 years), with Sanders stage 5, moderate to severe IS, and who have failed nonoperative management. This is in line with the eligibility criteria for the single-center, non-randomized clinical study that supported FDA approval of a first-generation VBT device (The Tether, Zimmer Biomet, Westminster, Colorado) under an Investigational Device Exemption (IDE) application (NCT02897453).39 These eligibility criteria included Cobb angles of 3065, which is reflected in the current US FDA indications. However, in our clinical practice surgery is typically offered for patients with Cobb angles greater than 40. In NCT02897453, 56% of patients had a Cobb angle >40 and 84% had a Cobb angle >35; the mean preoperative Cobb angle was 40.

Approval was obtained for NCT02897453 from the Western Institutional Review Board, and all patients provided written consent prior to study enrollment. The study was conducted according to the principles of good clinical practices as defined under the US FDA regulations and the International Conference on Harmonisation Guidance for Good Clinical Practice.

In our clinical experience, there are more spinal levels instrumented in spinal fusion surgery than VBT. With the lack of published comparative data, we conservatively assumed that patients would require operation over a mean of 7.625 vertebral levels, whether they received spinal fusion or VBT procedure. This was based on the number of instrumented levels reported for patients across the ongoing VBT observational study (NCT02897453), and another independent study in which patients received VBT.35,39

Spinal fusion was chosen as the relevant comparator for the CUA as it represents the current standard of care in our clinical practice in the US for pediatric patients aged >10 years with moderate to severe IS who have failed nonoperative management.

A Markov cohort state transition model with a quarterly cycle length was used to perform the CUA. The model was developed in Microsoft Excel version 1908. A Markov model was considered to be an appropriate and transparent choice of structure, given the potential for patients to experience, and recover from, multiple revision events.

A 15-year time horizon was chosen for the base case of the analysis, beginning with the index procedures. A long-term time horizon (lifetime) was not considered appropriate due to the immaturity of utility data available for the analysis; extensive extrapolation over such a time horizon would be associated with considerable uncertainty. However, differences in HRQoL outcomes for patients treated with VBT and spinal fusion (eg due to improved range of motion), if present upon reaching skeletal maturity, are anticipated to persist into the long term. Therefore, it was important to choose a time horizon of sufficient length to capture plausible mid- to long-term differences in HRQoL outcomes. Additional time horizons (5, 10, and 20 years) were explored in scenario analyses.

Patients entered the model in the spinal fusion or VBT index procedure health states, in which they incurred index procedure costs and were assigned preoperative utility. Patients could then transition to the postoperative health states, where no further costs were incurred, and patients were assigned mean postoperative utilities for the corresponding index procedure. Most patients remained in this state for the remainder of the time horizon. However, patients were modeled to be at risk of requiring revision procedures throughout the model time horizon and could transition to revision health states from any other health state, with the exception of a final absorbing health state where patients were not eligible for additional fusion revision procedures (Ineligible (Fusion) health state). In the revision health states, patients incurred revision procedure costs and were assigned preoperative utility. Patients in the VBT group were also modeled to be at risk of requiring a subsequent spinal fusion procedure.

Patients who received two spinal fusion revisions could transition to the absorbing Ineligible (Fusion) health state, to reflect the fact that clinicians would be unlikely to recommend more than two spinal fusion revisions in practice, even if some patients were not deriving utility benefit from their fusion procedure relative to preoperative HRQoL. This assumption thus avoids overestimating the costs of spinal fusion revisions in the long term. No such cap was placed on the number of VBT revisions that patients may receive, given that patients could escape to the spinal fusion health states. No death state was included in the model given that patients were young, and the procedures are not associated with a significant risk of death.43,51 Also, there is unlikely to be a difference in mortality between the procedures.52

Diagrams of the model structure for patients in the VBT and spinal fusion treatment groups are provided in Figure 2. Follow-up and monitoring costs were not included based on the assumption that resource use would be similar across the VBT and spinal fusion treatment groups. Costs and disutilities associated with complications of the procedures (outside of those that necessitate revisions) were not included in the analysis, given that it was assumed that resource-use relating to the management of complications would be similar across the VBT and spinal fusion treatment groups, and the HRQoL impact of complications was already captured in the mean postoperative utilities. Costs were presented in 2020 US dollars, and costs and benefits were discounted at a rate of 3% per year, as per the Institute for Clinical and Economic Reviews 20202023 Value Assessment Framework.49

Figure 2 Structure diagram. (A) VBT treatment group (B) fusion treatment group. The fusion treatment arm structure is same across both groups (dark grey boxes).

Abbreviation: VBT, anterior vertebral body tethering.

Model inputs were derived, where possible, from the most relevant values identified in the published literature. Three categories of inputs were estimated: transition probabilities, health state utility weightings, and cost and resource use inputs. Model input values can be found in Table 1 (see also Supplementary Tables 14).

Table 1 Model Parameter Estimates

To derive VBT revision rates, revision event data were pooled from the 88 patients included across NCT02897453 and Hoernschemeyer et al35,39 Calculations used to derive these rates are presented in Supplementary Table 1 A constant rate of VBT revision was assumed, allowing for the calculation of quarterly revision rates.

To derive spinal fusion revision rates, data were used from Ahmed et al, a large prospective study of fusion outcomes.40 Ahmed et al reported actuarial fusion survival at time points of 3 months, and 1, 2, 5, and 10 years after index surgery, where any spine re-operation was defined as a terminal event. The population of the study consisted of 1435 pediatric and young adult patients, with an average age of 15 years at surgery, who had spinal fusion to treat IS.40 Cobb angle and Sanders stage were not reported for this population. Calculations used to derive the spinal fusion revision rates are presented in Supplementary Table 2. The rate of spinal fusion revision by the 3-month time point was used to inform quarterly revision probabilities in the model for patients who had an index or revision procedure in the previous quarter. A constant rate of spinal fusion revision was assumed for 3 months to 10 years postoperatively and was used to inform quarterly revision probabilities in the model for patients who had not had an index or revision procedure in the previous quarter.

For both the VBT and spinal fusion revision probabilities, it was necessary to extrapolate revision probabilities, by assuming that they could be applied, without adjustment, across the full 15-year model time horizon. As specified, Ahmed et al had a maximum follow-up of 10 years, whereas NCT02897453 had a mean follow-up of 4.8 years (range: 27 years), and Hoernschemeyer et al 3.2 years (range: 2.25.2 years).35,39 Since re-revision rates were not identified in the literature, it was assumed that the rate of VBT or spinal fusion revision was independent of the number of prior revisions.

Transition probabilities from VBT health states to the spinal fusion index procedure health state were calculated using the rate at which patients with VBT underwent subsequent fusion in the pooled population of NCT02897453 and Hoernschemeyer et al.35,39 Based on our clinical experience, we assumed that patients could not have a spinal fusion index procedure within one-quarter of a VBT index procedure. Separate probabilities were calculated for patients who had just had an operation (eg revision VBT procedure in the previous quarter), and those who had not, based on follow-up for patients with and without prior VBT revisions in the pooled population of NCT02897453 and Hoernschemeyer et al, respectively.35,39 Due to a lack of data on HRQoL and revision rates experienced by patients that received spinal fusion following VBT, these patients were modeled identically to patients in the spinal fusion treatment group.

Three utility weightings were applied to health states in the model; preoperative utility, a mean postoperative utility following VBT and a mean postoperative utility following spinal fusion. Data from NCT02897453 were used to derive the mean postoperative VBT utility, and data from Aghdasi et al to derive the mean postoperative spinal fusion and preoperative utilities.39,43 This was a large meta-analysis that reported preference-based outcomes for 1494 pediatric and young adult patients that underwent spinal fusion for the treatment of IS, with a mean age of 14.6 years.43 Cobb angle and Sanders stage was not reported for this population.

Scoliosis Research Society Outcomes Questionnaire (SRS-22r) scores were reported for both the NCT02897453 and Aghdasi et al cohorts.39,43 For VBT, scores from the NCT02897453 cohort were reported over a range of time points, from 2789 months after index surgery.39 For spinal fusion, Aghdasi et al reported three sets of mean scores from their cohort, the first at 24 months prior to index surgery, the second at 24 months after index surgery, and the third over the range >60 months after index surgery.43

An algorithm from Wong et al was used to convert these scores to EuroQol 5-Dimension (EQ-5D) index scores.51 Model 2 from this publication was chosen based on available data and goodness-of-fit statistics. In the base case of the model, the algorithm was applied to the mean SRS-22r outcome scores calculated from all reports in the NCT02897453 cohort to generate postoperative VBT utility.39 To generate the postoperative spinal fusion utility, the algorithm was applied to a weighted average (based on number of reports) of the mean SRS-22r outcome scores from Aghdasi et al 24 months after index surgery and >60 months after index surgery.43 Given that patients eligible for VBT would otherwise receive spinal fusion in clinical practice and that preoperative utility data were not available from NCT02897453, we assumed that preoperative utility for patients eligible for spinal fusion would be applicable to the modelled population. Therefore, we applied the algorithm to the mean SRS-22r outcome scores at 24 months prior to index surgery from Aghdasi et al to generate preoperative utility.43

Since the latest reports from NCT02897453 and the majority of reports from Aghdasi et al were recorded at <8 years after index surgery, we assumed that the postoperative utilities derived from these sources would persist across the 15-year base case time-horizon of the model.39,43 However, scenario analyses were performed in which time-dependent postoperative utilities were applied, based on variation in the mean SRS-22r scores across the two postoperative timepoints in Aghdasi et al.43

The CUA was conducted from the perspective of the US IDS, and as described above, costs due to follow-up and monitoring, and the treatment of complications (other than those necessitating revisions), were not considered. Costs were included for VBT and spinal fusion index and revision procedures.

Medicare payments were used as a proxy for provider costs, as per the cost analysis by Luhmann et al.42 The cost of an index spinal fusion procedure was calculated as the sum of hospital inpatient facility costs and physician professional fees associated with the procedure. Hospital inpatient facility costs were based on Medicare diagnosis-related group (DRG) data, and physician fees on current procedural terminology (CPT) data.53,54 The calculations used to derive the total cost of the index spinal fusion procedure are detailed in Supplementary Table 1.

Due to a lack of available data, revision of spinal fusion was assumed to have the same cost as the index procedure. In practice, some revision spinal fusion procedures may have lower costs if constructs are not replaced. A scenario analysis was performed in which revision spinal fusion procedure costs were reduced to address this possibility.

The cost of an index VBT procedure was calculated based on the assumption that the non-device costs of the index VBT procedure are equal to the non-device costs of the index spinal fusion procedure. The calculations used to derive the cost of the index VBT procedure are detailed in Supplementary Table 3.

Since the inpatient DRG payments for an index spinal fusion procedure are bundled to include the spinal fusion device cost, the non-device costs for the spinal fusion procedure were calculated by subtracting an estimated spinal fusion device cost from the index fusion procedure cost. The estimate of $17,200 was based on an independent survey of spinal surgeons in the US and is in line with existing fusion costing studies.4447 The VBT device cost was calculated based on unit costs for VBT device components and mean component usage recorded across NCT02897453 and Hoernschemeyer et al.35,39 Unit costs for VBT device components were based on list prices given by the manufacturer of a first-generation VBT device.

The cost of revision of VBT was calculated based on the following assumptions: non-device costs are identical to the index procedure; new VBT cords are required in 50% of revisions, and 2 additional levels are operated on in 50% of revisions. This resulted in a reduced cost relative to the VBT index procedure. These assumptions were made based on NCT02897453 and the Hoernschemeyer et al study, in which roughly half of VBT revision procedures required only a cord cut and no additional implant costs.35,39

A probabilistic and a deterministic sensitivity analysis (PSA and DSA, respectively) were conducted to test the robustness of the model results. For the DSA, inputs were varied by the standard deviation when available. Standard deviation was chosen to reflect a suitable degree of variation in these inputs; standard error was judged to result in too little variation to demonstrate the sensitivity of the results to the inputs. In the absence of data on standard deviation for inputs, inputs were varied by 20%. The standard deviation for all utility weightings was set at 7% of the mean, based on the standard deviation calculated for the postoperative VBT utility.43 VBT-to-revision and VBT-to-fusion transition probabilities that could not be varied in the DSA (as they formed sets of co-dependent probabilities) were varied manually. Standard distributions for health economic methodology were used in the PSA, and 1000 simulations were run.55

Scenario analyses were performed to investigate the impact of alternative assumptions and input values. The results of the DSA were used to inform the selection of scenario analyses, with priority given to those inputs and assumptions to which the model results were most sensitive. These included the postoperative utility weightings and index procedure costs.

The preoperative utility weightings and revision procedure costs were shown to have little impact on results when varied in the DSA. Also, data were not available to support alternative assumptions or inputs for these parameters. Therefore, scenario analyses were not performed focusing on these parameters. Since the preferences of healthcare providers and payers for more immediate returns on investment may vary, both the time horizon and discounting rates (benefits and costs) were varied in scenario analyses. The time horizon was varied to 5, 10, and 20 years, and discounting rates were varied to 0 and 5%. Two scenario analyses were performed investigating alternative assumptions for utility weightings, where data were available to support alternative assumptions and inputs. Firstly, an alternative SRS-22r to EQ-5D mapping algorithm with a similar goodness of fit, Model 1 from Wong et al, was utilized to calculate the utility inputs.51 Secondly, the mean SRS-22r outcome scores over the range >60 months after index surgery from Aghdasi et al were used to calculate a postoperative spinal fusion utility that was applied after 5 years in the model, rather than applying a utility based on the weighted average of scores at 24 months and >60 months throughout the model time-horizon.43

A costing scenario was performed in which non-device costs for VBT procedures were assumed to be 80% of non-device costs for spinal fusion procedures, as opposed to 100%. This scenario was performed because VBT procedures may have lower non-device costs than spinal fusion procedures. An additional costing scenario was performed in which revision of spinal fusion costs was reduced by 50% to reflect the fact that some fusion revision procedures may have reduced costs if constructs are not replaced. Finally, a set of scenarios were performed in which the VBT revision rates were changed. Quarterly VBT revision rates were varied to produce cumulative 2-year VBT revision probabilities of 10%, 20%, and 40% per patient. The upper limit of these probabilities, 40%, was based on a retrospective study from Newton et al where 7 of 17 patients underwent revisions over a mean follow-up of 2.5 years (range: 24 years).56

In the base case analysis, over the 15-year time horizon, VBT was associated with an estimated 11.30 total discounted QALYs as compared with 10.76 for spinal fusion, an incremental gain of 0.54 (Table 2). The total discounted costs were estimated to be $96,897 for VBT whereas the total costs considered for spinal fusion were estimated to be $51,351, a difference of $45,546. The resulting incremental cost-effectiveness ratio (ICER) for VBT versus spinal fusion was $84,391. At a WTP threshold of $100,000 per QALY gained, the higher costs associated with VBT were offset by the higher QALYs gained, yielding a net monetary benefit (NMB) of $8424.

Table 2 Cost-Effectiveness in the Base Case Analysis

A scatterplot of 1000 probabilistic simulations is presented in Figure 3, revealing a low level of variability in the results. At a WTP threshold of $100,000 per QALY gained, VBT was cost-effective in 66.4% of simulations (Figure 4). The mean probabilistic results were similar to the base case results, with incremental costs and QALYs of $45,700 and 0.54, respectively, resulting in an incremental cost per QALY gained of $84,676 for VBT as compared with spinal fusion.

Figure 3 PSA Scatterplot of 1000 simulations on an incremental cost-effectiveness plane. Dashed line indicates WTP threshold used in this analysis, corresponding to the lower end of the range recommended by the WHO-CHOICE guidelines.49,50

Abbreviations: PSA, probabilistic sensitivity analysis; QALYs, quality-adjusted life years; VBT, anterior vertebral body tethering; WHO, World Health Organization; WTP, willingness-to-pay.

Figure 4 Cost-effectiveness acceptability curve. Dashed line indicates WTP threshold used in this analysis, corresponding to the lower end of the range recommended by the WHO-CHOICE guidelines.49,50

Abbreviations: VBT, anterior vertebral body tethering; WHO, World Health Organization; WTP, willingness-to-pay.

The DSA indicated that cost-effectiveness results were most sensitive to variation in the postoperative utility weightings (Figure 5), followed by index procedure costs for VBT and spinal fusion. A threshold analysis found that a minimum VBT postoperative utility of 0.918 (base case value 0.925) was required for an ICER below $100,000 (provided the base case fusion postoperative utility of 0.877 is used), equating to a difference of 0.041 between the postoperative VBT and fusion utility weightings. The results were less sensitive to variations in the transition probabilities, including revision probabilities, the preoperative utility weightings, and the cost of revision procedures. Manual variations in the VBT revision probability and spinal fusion probabilities for patients in the VBT group were found to have little effect on model results. Varying the VBT revision probability by 20%, while keeping the spinal fusion probabilities constant, produced ICERs of $89,801 and $79,032, respectively. Varying the aforementioned spinal fusion probabilities by 20%, while keeping VBT revision probabilities constant, produced ICERs of $86,667 and $82,124, respectively.

Figure 5 One-way sensitivity analysis. Sensitivity of NMB (based on a WTP threshold of $100,000/QALY) to changes in top 10 model parameters; lowering the parameter indicated in blue, increasing the parameter indicated in purple. Postoperative (Index Fusion) to Revision 1 (Fusion) is the probability of revision without prior spinal fusion in the last three months; Index (Fusion) to Revision 1 (Fusion) is the probability of revision with prior spinal fusion in the last three months. Please note that the VBT revision probabilities were not varied in the DSA, as they could not be varied in isolation of other independent parameters; these probabilities were instead varied manually, and the results are reported in the sensitivity analyses section.

Abbreviations: NMB, net monetary benefit; DSA, deterministic sensitivity analysis; QALYs, quality-adjusted life years; VBT, anterior vertebral body tethering; WTP, willingness-to-pay.

The results of scenario analyses that were performed are presented in Figure 6. Varying the 15-year time horizon over which costs and QALYs were accrued had a large effect on the ICER. Time horizons of 5 years, 10 years, and 20 years produced ICERs of $181,051, $107,760 and $73,045, respectively. VBT becomes cost-effective as compared with spinal fusion within the 12th year after index procedure. The dependency of the ICER on the length of time horizon is presented in Figure 7; extending the time horizon was shown to lower the ICER. Varying the discounting rates for costs and benefits from 3% to 0% was favorable for VBT, while increasing these rates to 5% had the opposite effect, producing ICERs of $73,528 and $92,131, respectively. Using the alternative SRS-22r to EQ-5D mapping algorithm from Wong et al produced an ICER of $70,523.51 Applying 5-year postoperative spinal fusion utility after the 5-year time point produced an ICER of $116,680. The costing scenario in which non-device costs for VBT procedures were set equal to 80% of non-device costs for spinal fusion procedures produced an ICER of $70,037. The costing scenario in which fusion revision procedure costs were reduced by 50% produced an ICER of $89,236. The scenarios in which the quarterly VBT revision rates were varied to produce cumulative 2-year VBT revision probabilities of 10%, 20%, and 40% produced ICERs of $103,366, $157,745 and $310,388, respectively. A threshold analysis was performed indicating that a cumulative 2-year VBT revision probability of 9.3% or below was required to produce an ICER below $100,000, exceeding the base case value of 6.02%.

Figure 6 Scenario analysis ICERS. Dashed line indicates WTP threshold used in this analysis, corresponding to the lower end of the range recommended by the WHO-CHOICE guidelines.49,50

Abbreviations: EQ-5D, EuroQol 5-Dimension; ICERs, incremental cost-effectiveness ratios; QALYs, quality-adjusted life years; SRS-22r, Scoliosis Research Society Outcomes 22-Item Questionnaire; VBT, anterior vertebral body tethering; WHO, World Health Organization; WTP, willingness-to-pay.

Figure 7 ICER versus time horizon. Vertical dashed line indicates the 15-year time horizon used in the base case; horizontal dashed line indicates WTP threshold used in this analysis, corresponding to the lower end of the range recommended by the WHO-CHOICE guidelines49,50

Abbreviations: ICER, incremental cost-effectiveness ratio; QALYs, quality-adjusted life years; WHO, World Health Organization; WTP, willingness-to-pay.

The results of this analysis suggest that, from the perspective of the US IDS, VBT may be a cost-effective treatment compared with fusion for pediatric patients with IS. The deterministic and probabilistic ICERs of $84,391 and $84,676 per QALY gained, respectively, are below the recommended US WTP threshold of $100,000.57 At this WTP threshold, VBT was cost-effective in 66.4% of probabilistic iterations, suggesting that the results are robust with respect to combined parameter uncertainty, although the limitations associated with studies reporting clinical outcomes for the VBT procedure should be considered in the interpretation of these findings.

At the time of these analyses, studies reporting clinical outcomes for the VBT procedure include relatively small patient numbers,3438 with a small subset of those who reported key patient-reported outcomes34,35 needed for a cost-effectiveness analysis as compared to the extensive reporting of studies describing spinal fusion for pediatric patients with IS spanning decades and large sample sizes.7,43 Also, studies reporting clinical outcomes for the VBT procedure provide a maximum length of follow-up of 7 years, whereas the base case time horizon for the CUA was 15 years.

The mean postoperative utility weightings following VBT and spinal fusion are the key sources of uncertainty in the cost-effectiveness results. Clinical plausibility for the differences in postoperative utility weightings includes the difference in mechanism of action between the two surgical interventions, with spinal fusion inherently limiting mobility and VBTs tethering mechanism relying on (and therefore not hindering) continued growth and range of motion. VBT has the potential to increase mobility and range of motion as compared to spinal fusion,14 which may result in improved HRQoL in the long term, underpinning the differences in postoperative utility weightings.

The VBT revision rate scenarios produced ICERs that were considerably larger than the base case ICER. However, these scenarios modeled much higher VBT revision rates compared with those observed from the 88 patients included across NCT02897453 and Hoernschemeyer et al.35,39 The retrospective study from Newton et al which informed these scenarios involved a much smaller sample size (17 versus 88), and thus the revision rate observed in this study is subject to greater uncertainty.56 Insufficient data were available from this study to pool alongside NCT02897453 and Hoernschemeyer et al.

This analysis differs in several ways from previous analyses of surgical correction for IS. Most notably, to the best of our knowledge no previous cost-effectiveness analyses have been published for VBT. Additionally, there exist very few cost-effectiveness analyses for surgical treatment of IS across the literature; previous analyses of surgical interventions are generally limited to costing analyses and do not consider differences in utility, and thus there is a lack of precedence for what constitutes appropriate methodology for cost-effectiveness analysis in this setting.41,42,58,59

Finally, our analysis evaluated costs and benefits over a 15-year time horizon in the base case, whereas other recent cost analyses for pediatric scoliosis report on 6-year time horizons,41,42 or shorter.58,59 A longer time horizon was appropriate for the present study because although the majority of costs of surgical interventions in IS are likely to be accrued in a short period following the index surgery, clinical benefits, such as range of motion and return to normal activities, may plausibly be much longer lasting. Also, the time horizon was selected to align with the consensus-based recommendations from the US panel on Cost-effectiveness in Health and Medicine.57,60

This was the first CUA conducted for VBT. Where assumptions were required, consideration was given to their clinical plausibility based on our clinical experience in the US, and conservative assumptions were made where necessary. For example, our results suggest that VBT may be cost-effective as compared to spinal fusion even though the WTP threshold chosen represents the conservative lower range of recommended thresholds, as per ICER and WHO guidelines.49,50

Uncertainty in the model was explored through DSA and PSA. Additionally, the impacts of key assumptions and inputs to which the model was particularly sensitive were tested with scenario analyses. Scenario analyses in general revealed a low amount of variability. Although the results were very sensitive to the length of time horizon selected, this was expected as VBT has larger upfront costs and a long-term utility benefit compared to spinal fusion.

This CUA would benefit from further research into postoperative utilities, particularly VBT postoperative utility, as there were uncertainties in their estimation, and they were shown to have a large impact on model results when varied in the DSA. Uncertainties derive from the small sample size of NCT02897453 (N=57) that was used to determine the VBT postoperative utility. Additional uncertainties arise from differences between the patient populations used to derive the spinal fusion and VBT postoperative utilities.39,43

While fusion represents the current standard of care in the US for pediatric patients aged >10 years of age who have failed non-operative management, fusion is not limited to skeletally immature patients and is therefore used in a broader patient population than VBT. As this is the first CUA for VBT and no head-to-head prospective studies have been conducted for VBT versus fusion, data for the target patient population are limited. Thus, the inputs for VBT and fusion used in this model are derived from populations that differ in several respects. For example, the mean age at the time of surgery for patients in NCT02897453 was 12.4 years, and the mean age at the time of surgery for patients undergoing spinal fusion in the Aghdasi et al cohort was 14.6 years. It is unclear whether these populations can be considered fully comparable. No adjustments were made to account for factors such as age difference between the cohorts or curve magnitude, which is typically greater in cohorts undergoing spinal fusion. It is worth noting that utilities, as measured by SRS-22r, have been reported to reduce as children progress through adolescence.61 The patient population was defined as per current US FDA indications based on Sanders stage and Cobb angle, which were not reported for the published populations used to derive revision rate and utility inputs.40,43 We were therefore not able to confirm a Sanders stage or Cobb angle match between our patient population and the populations used to derive these model inputs. Despite these limitations, we feel we have used the most appropriate inputs available to derive a plausible estimate and hope that our model serves as a framework for future work once more data become available.

On the other hand, revision rates of spinal fusion are higher in skeletally immature patients, and we reported fusion revision rates based on patients who were older than those undergoing VBT. Thus, revision rates for spinal fusion may be under-estimated by this model. Additionally, the current model uses a 2-year cumulative revision rate for VBT of 6.02%; however, there is a wide range of published tethering revision rates from 040%.35,36,56 The uncertainty in VBT revision rates may be due to small sample sizes of existing studies, follow-up timeframe variation or variability in surgeon experience; further investigation is warranted.

In our experience, the efficacy of VBT procedures may differ between thoracic/lumbar tethering, so differences in patient populations in this respect could result in differing postoperative utility independent of the intervention received, although there are limited data available to confirm. Similarly, we considered postoperative care to be equivalent between VBT and fusion as there are limited data evaluating any differences between the two procedures. Any reduction in VBT procedural costs over time would result in improvements in the cost-effectiveness estimates. Additionally, the aggregate data used to inform the model comprised all Lenke curve types, and VBT may only be appropriate for select flexible curve types such as Lenke 1 and 5 patterns.

The scenario analyses presented here highlight the need for longer-term VBT postoperative utility data. SRS-22r scores reported >60 months after index surgery in Aghdasi et al had improved relative to those reported at 24 months. Therefore, the scenario analysis where a postoperative spinal fusion utility derived from the outcome scores >60 months after index surgery was applied after 5 years in the model produced an ICER over the $100,000 WTP threshold.43 Utility data at time points >60 months were available for VBT patients in NCT02897453, however were not considered given the comparatively low number of patients being followed up beyond this time point, which would likely introduce further uncertainty around postoperative utilities.

In addition to the above, some assumptions were made in the face of uncertainty and could not be explored in scenario analyses, as there were not the data to suggest plausible alternative scenarios. These assumptions included that patients treated with VBT and subsequent fusion could be treated identically to patients treated with fusion alone, that a patient could undergo a maximum of two fusion revisions, and that revision rates were independent of the number of prior revisions. It is uncertain how well these assumptions reflect real-world practice due to a lack of available data. However, the first two assumptions were unlikely to have had a large effect because only a small proportion of patients received both index VBT and index fusion procedures or reached the Ineligible (Fusion) absorbing health state, due to the low probabilities involved. In the VBT group, 6% of patient time was spent in fusion health states, and the percentage of total patient time spent in the Ineligible (Fusion) state was less than 0.1% in either treatment group. The third assumption is unlikely to have a large effect due to the low impact that variations in revision probabilities had on model results (as demonstrated in the DSA).

This is the first cost-effectiveness analysis comparing VBT with spinal fusion in pediatric patients with IS. The results of the analysis suggest that VBT may be considered cost-effective compared with spinal fusion from the US IDS perspective if a decision-maker is willing to pay at least $84,391 per QALY gained, as VBT provides additional health gains, which represent efficient resource use despite higher initial costs. On threshold analysis of revision surgery rates, VBT remained cost-effective up to a 2-year cumulative revision probability of 9.3%. With base case assumptions, VBT became cost-effective in the 12th year after index surgery, with a cumulative 2-year revision rate of 6.02% for VBT and 3.2% for spinal fusion. Further analyses with larger VBT sample sizes, longer-term VBT data, and head-to-head studies are warranted to help address remaining uncertainties and inform decision-making for the most appropriate treatment for pediatric patients.

The authors are not able to share the data from the IDE study (NCT02897453) for a number of reasons. These include that the information is part of an ongoing FDA IDE study in support of a product approval; these data are proprietary and solely owned by Zimmer Biomet and Shriners Hospital.

The authors thank the patients and their caregivers, as well as the investigators and their teams who took part in the NCT02897453 study. This study was funded by Zimmer Biomet. This work was presented at the 14th International Congress on Early Onset Scoliosis (virtual, November 14, 2020).

DWP is consultant for SI-Bone, Globus; reports royalties from Springer; royalties to institution from Globus and Medtronic; research support from Medtronic, Mizuho OSI, and AO Spine. ANL is consultant with research support from Globus, Medtronic, DePuy Synthes and Orthopediatrics. In addition, ANL has a patent US10667845 B2 issued. AFS is a paid consultant for DePuy, Ethicon, Globus Medical, Misonix, Picara, Mirius, and Stryker; paid consultant and IP royalties from NuVasive, Zimmer Biomet; Board or committee member of Pediatric Spine Study Group and Setting Scoliosis Straight Foundation. WR, HB, AP, WM are employees of Costello Medical Consulting Ltd; report consultancy fees from Zimmer Biomet for development of the model, editorial support and publication coordination. RD is an employee and shareholder of Zimmer Biomet. The authors report no other conflicts of interest in this work.

1. Cheng JC, Castelein RM, Chu WC, et al. Adolescent idiopathic scoliosis. Nat Rev Dis Primers. 2015;1(1):15030. doi:10.1038/nrdp.2015.30

2. Dunn J, Henrikson NB, Morrison CC, et al. Screening for adolescent idiopathic scoliosis: evidence report and systematic review for the US preventive services task force. JAMA. 2018;319(2):173187. doi:10.1001/jama.2017.11669

3. Konieczny MR, Senyurt H, Krauspe R. Epidemiology of adolescent idiopathic scoliosis. J Child Orthop. 2013;7(1):39. doi:10.1007/s11832-012-0457-4

4. Sato T, Hirano T, Ito T, et al. Back pain in adolescents with idiopathic scoliosis: epidemiological study for 43,630 pupils in Niigata City, Japan. Eur Spine J. 2011;20(2):274279. doi:10.1007/s00586-010-1657-6

5. Helenius L, Diarbakerli E, Grauers A, et al. Back pain and quality of life after surgical treatment for adolescent idiopathic scoliosis at 5-year follow-up: comparison with healthy controls and patients with untreated idiopathic scoliosis. J Bone Joint Surg Am. 2019;101(16):14601466. doi:10.2106/JBJS.18.01370

6. Ramirez N, Johnston CE, Browne RH. The prevalence of back pain in children who have idiopathic scoliosis. J Bone Joint Surg Am. 1997;79(3):364368. doi:10.2106/00004623-199703000-00007

7. Larson AN, Baky F, Ashraf A, et al. Minimum 20-year health-related quality of life and surgical rates after the treatment of adolescent idiopathic scoliosis. Spine Deform. 2019;7(3):417427. doi:10.1016/j.jspd.2018.09.003

8. Weinstein SL, Zavala DC, Ponseti IV. Idiopathic scoliosis: long-term follow-up and prognosis in untreated patients. J Bone Joint Surg Am. 1981;63(5):702712. doi:10.2106/00004623-198163050-00003

9. Asher MA, Burton DC. Adolescent idiopathic scoliosis: natural history and long term treatment effects. Scoliosis. 2006;1(1):2. doi:10.1186/1748-7161-1-2

10. Bridwell KH. Surgical treatment of idiopathic adolescent scoliosis. Spine (Phila Pa 1976). 1999;24(24):26072616. doi:10.1097/00007632-199912150-00008

11. Weiss HR, Goodall D. Rate of complications in scoliosis surgery - a systematic review of the PubMed literature. Scoliosis. 2008;3(1):9. doi:10.1186/1748-7161-3-9

12. Kim YJ, Lenke LG, Cho SK, et al. Comparative analysis of pedicle screw versus hook instrumentation in posterior spinal fusion of adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2004;29(18):20402048. doi:10.1097/01.brs.0000138268.12324.1a

13. Danielsson AJ, Romberg K, Nachemson AL. Spinal range of motion, muscle endurance, and back pain and function at least 20 years after fusion or brace treatment for adolescent idiopathic scoliosis: a case-control study. Spine. 2006;31(3):275283. doi:10.1097/01.brs.0000197652.52890.71

14. Pahys JM, Samdani AF, Hwang SW, et al. Anterior vertebral body tethering for adolescent idiopathic scoliosis preserves trunk motion compared to posterior spinal fusion at two year follow-up. Scoliosis Research Society Annual Meeting. Virtual, Spine Deformity; 2020.

15. Helenius I, Remes V, Yrjnen T, et al. Comparison of long-term functional and radiologic outcomes after Harrington instrumentation and spondylodesis in adolescent idiopathic scoliosis: a review of 78 patients. Spine. 2002;27(2):176180. doi:10.1097/00007632-200201150-00010

16. Padua R, Padua S, Aulisa L, et al. Patient outcomes after Harrington instrumentation for idiopathic scoliosis: a 15- to 28-year evaluation. Spine. 2001;26(11):12681273. doi:10.1097/00007632-200106010-00019

17. Haapala H, Saarinen AJ, Salonen A, et al. Shilla growth guidance compared with magnetically controlled growing rods in the treatment of neuromuscular and syndromic early-onset scoliosis. Spine. 2020;45(23):E1604E1614. doi:10.1097/BRS.0000000000003654

18. Luhmann SJ, McCarthy RE. A comparison of shilla growth guidance system and growing rods in the treatment of spinal deformity in children less than 10 years of Age. J Pediatr Orthop. 2017;37(8):e567e574. doi:10.1097/BPO.0000000000000751

19. Nazareth A, Skaggs DL, Illingworth KD, et al. Growth guidance constructs with apical fusion and sliding pedicle screws (SHILLA) results in approximately 1/3rd of normal T1-S1 growth. Spine Deform. 2020;8(3):531535. doi:10.1007/s43390-020-00076-7

20. Bess S, Akbarnia BA, Thompson GH, et al. Complications of growing-rod treatment for early-onset scoliosis: analysis of one hundred and forty patients. JBJS. 2010;92(15):25332543. doi:10.2106/JBJS.I.01471

21. Myung KS, Skaggs DL, Thompson GH, et al. Nutritional improvement following growing rod surgery in children with early onset scoliosis. J Child Orthop. 2014;8(3):251256. doi:10.1007/s11832-014-0586-z

22. Watanabe K, Uno K, Suzuki T, et al. Risk factors for complications associated with growing-rod surgery for early-onset scoliosis. Spine. 2013;38(8):E4648. doi:10.1097/BRS.0b013e318288671a

23. Abdelaal A, Munigangaiah S, Trivedi J, et al. Magnetically controlled growing rods in the treatment of early onset scoliosis: a single centre experience of 44 patients with mean follow-up of 4.1 years. Bone Jt Open. 2020;1(7):405414. doi:10.1302/2633-1462.17.BJO-2020-0099.R1

24. Akbarnia BA, Pawelek JB, Cheung KM, et al. Traditional growing rods versus magnetically controlled growing rods for the surgical treatment of early-onset scoliosis: a case-matched 2-year study. Spine Deform. 2014;2(6):493497. doi:10.1016/j.jspd.2014.09.050

25. Arhewoh RE, Mo M, Luhmann SJ. Analysis of 280 magnetically controlled growing rod lengthenings comparing external remote control readouts and radiographic measurements: impact of patient and deformity factors. J Pediatr Orthop. 2021;41(2):e105e110. doi:10.1097/BPO.0000000000001678

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[Full text] Cost-utility analysis of anterior vertebral body tethering | CEOR - Dove Medical Press

In theory, product claims provide the strongest patent protection because they are not limited to the use or preparation of the Traditional Chinese Medicine (TCM) product. In reality, however, infringement assessment often involves looking at the methods used to prepare the TCM product.

Traditional Chinese Medicine, or TCM, is a subset of herbal medicine. TCM patent applications generally fall into four categories.

These categories reflect the main objectives of TCM patent protection: namely, to protect the formula, craft, original materials, and commercial products.

Method Claims

Method claims are useful when the TCM products preparation, purification, or extraction process is innovative, but the final composition is unclear. Its important to define the claim form based on the characteristics of raw materials, the process, and dosage. Raw materials should include all components and proportions used to prepare the TCM product. The process should include all steps and conditions, such as temperature, pressure, time, etc. The dosage can be broadly described as medicament, if a person skilled in the art could understand what that means in light of the patent; otherwise, the dosage needs to be specific. Below is an example of a TCM method claim:

A method for producing a medicine for postpartum treatment, prepared from:20-30 parts by weight of motherwort, 3-9 parts by weight of angelica, 1-6 parts by weight of ginseng, 6-12 parts by weight of astragalus, and 5-13 parts by weight of Polygonum multiflorum, Peach kernels 4-7 parts by weight, Cyperus rotundus 6-9 parts by weight, mixed with water and decocted twice, the amount of water added each time is 10 times the amount of raw materials, and the decoction is 1-3 hours each time. The decoction is combined, filtered, and the filtrate is concentrated into a clear paste with a relative density of 1.25 to 1.28, 40 to 70 parts by weight of brown sugar and 5 to 10 parts by weight of dextrin are added to make granules, which are dried into granules.

A method claims scope extends to the product obtained by the method. Article 11 of Chinas Patent Law provides that after the invention patent right is granted, unless otherwise provided in this law, no entity or individual may exploit the invention without the permission of the patentee, that is, not use, promise to sell, sell, or import products directly obtained in accordance with the patented method.

Use Claims

Use claims are useful when the TCM products application is innovative.The Examination Guidelines provides this basic formula: The application of substance X in the preparation of therapeutic drug Y. Further, if effective ingredients are known, the claim can be written as [t]he application of substance X in the preparation of therapeutic drug Y, where the effective ingredients are Z.

A use claims scope, however, is limited to the claimed use.Therefore, obtaining a corresponding method claim is advantageous when applicable to protect the preparation, packaging, and promotion of the TCM products.

Product Claims

Lastly, product claims are useful when the TCMs final composition is known. In theory, they provide the strongest patent protection because they are not limited to the use or preparation of the TCM product. In reality, however, infringement assessment often involves looking at the methods used to prepare the TCM product. The bottom line is that there needs to be sufficient evidence that a product prepared by a different method is the same product prepared by the inventor.

As discussed before, method claims are useful when the TCM products preparation, purification, or extraction process is innovative, but the final composition is unclear. Most TCM patents fall under this category and these patents present some unique challenges in litigation.

For example, Beijing Yadong Biopharmaceutical Co., Ltd. (Yadong) and Guizhou Kangna Shengfang Pharmaceutical Co., Ltd. (Kangna) were involved in a TCM patent dispute in the Beijing No. 1 Intermediate Peoples Court. [(2006)??????8603?.] The Court found that claim 3 of Patent No. ZL02134148.6 was different from Yadongs TCM capsules. Specifically, the Court found that in claim 3, Fructus corni is decocted three times with waterdrug residue plus 5 times the amount of 90% ethanol for reflux extraction twice, 1 hour each time, where Yadongs capsule was Fruit Cornus plus ethanol refluxed for a second timedrug residue for use, which constituted a significant difference.Therefore, the prescription and preparation method of Yadongs capsules did not fall within the protection scope of claim 3.

Another example includes the appeal of a patent infringement dispute between Guizhou Baixiang Pharmaceutical Co., Ltd. (Baixiang) and the patent owner Zhao Shusheng. [(2011)???????6?.] Baixiang, the defendant, obtained drug registration approval and disclosed its preparation method in the drug label. The most significant difference is that the asserted patent recites using two ethanol reflux and the defendant adopted the technique of three ethanol refluxes, and the time of each reflux was also different.

The plaintiff argued that three-reflux and two-reflux are technologically equivalent. The Court disagreed for two reasons. First, although three-reflux and two-reflux both extract the active ingredients from yantuo, the plaintiff did not provide sufficient evidence that they achieve the same extraction results. Second, the defendant showed that three-reflux had far better extraction results than two-reflux. Plaintiffs witnesses also admitted that increasing the number of refluxes was more efficient.

These are typical examples of TCM patent disputes where the active ingredients are mostly characterized by extraction and preparation methods, making it difficult to enforce patent rights.

TCM, as a subset of herbal medicine, has similar patent protection principals and challenges in the United States. Composition claims are useful when the active ingredients are known and can be limited to a specific use. For example, Frisun, Inc. (Wuhan, China) obtained U.S. Patent No. 7,575,772 on Process and composition for syrup and jam from Luo Han Guo fruit that brings all the advantages of Luo Han Guo together to meet todays market demand for a natural, sugar-free sweetener. In TCM research, Luo Han Guo (or Monk fruits) is known to have the potential to be natural sweetener with a low glycemic index and can therefore be an alternative to sugar for diabetic populations. See, e.g., Ying. Z., Yan. Z., Jeff. E., Chi-Fu. H., Insulin secretion stimulating effects of mogroside V and fruit extract of Luo Han Kuo (Siraitia grosvenori Swingle) fruit extract., Acta Pharmaceutica Sinica., 44 (11): 1252-1257 (2009).

The number of patent acquisitions for herbal medicines has grown significantly.From 1976 to 2003, the U.S. Patent and Trademark Office (USPTO) granted a total of 1,968 herbal patents. [Surge in US patents on botanicals, NATURE BIOTECHNOLOGY VOLUME 22 NUMBER 6 JUNE 2004.] Since 2019, the USPTO has received more than 4,000 herbal patent applications since 2019. This number is fairly conservative, because many new application forms have not yet been made public.Below are a few:

Patent protection for TCM can present many challenges because of the various types of TCM products and the uncertainty of the active ingredients. As herbal medicine patents become more popular, we can expect to see similar challenges in enforcing patent rights in herbal medicine technology.

Shui Li is an intellectual property lawyer with Robins Kaplan. Her experience is in cross-border disputes, and she has worked with a variety of technology industries, including medicinal chemistry, biotechnology, video streaming, telecommunication, and semiconductors.

Yongfeng Zheng is General Counsel of Tasly Holding Group Co. Ltd. He holds a Doctor of Law, Master of Medicine, and is Vice-President of China Patent Protection Association.

Chunxuan Li is a partner and patent attorney at the Beijing Lifang Law Firm.

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Protecting Traditional Chinese Medicine Products in the United States and China - IPWatchdog.com

MANHASSET, N.Y.--(BUSINESS WIRE)--The burgeoning scientific field of bioelectronic medicine, which features the use of electronic devices to stimulate nerves to treat disease, has shown great promise in alleviating serious health conditions. In a Lancet Rheumatology editorial published, Feinstein Institutes for Medical Research president and CEO Kevin J. Tracey, MD, discussed a recent clinical study that used a hand-held battery-operated electronic device to treat patients suffering from moderate to severe rheumatoid arthritis (RA).

Researchers in a multicenter, uncontrolled, open-label study led by Marsal S, Corominas H, et al., published their findings in Lancet Rheumatology which observed the effects of daily up to 30 minutes of sensory branch stimulation therapy of the vagus nerve. The results showed significant changes in the disease activity and ultrasound and magnetic resonance imaging (MRI) revealed significant improvements. The authors conclude that this alternative treatment should be evaluated in larger controlled studies for RA.

In a thorough review of the research paper, Dr. Tracey, who has been heralded as the founding father of bioelectronic medicine for his discovery of the bodys inflammatory reflex, weighed in on the new findings. Some points raised include the need to better understand what part of the body this stimulation activated and the need for larger controlled clinical trials to answer important questions, including the intensity of the stimulation and optimal length.

initial evaluation of evolving breakthroughs should not be based on what we do not know, but rather on whether the clinical trials are well defined and described, and whether others can replicate the results using appropriate statistics and analytics, notes Dr. Tracey in the Lancet Rheumatology editorial. Important new data from basic science and clinical trials can accelerate the pace of its evolution from alternative quackery to clinical adoption.

The Feinstein Institutes for Medical Research is known as the global scientific home of bioelectronic medicine. Bioelectronic medicine combines molecular medicine, neuroscience, and biomedical engineering to develop innovative therapies to treat various diseases and conditions through targeted stimulation of nerves, including paralysis, arthritis, pulmonary hypertension, and inflammatory bowel disease.

Feinstein Institutes researchers recently discovered that a small cluster of neurons within the brain is responsible for controlling the bodys immune response and the release of cytokines, which leads to inflammation in the body.

About the Feinstein Institutes

The Feinstein Institutes for Medical Research is the research arm of Northwell Health, the largest health care provider and private employer in New York State. Home to 50 research labs, 3,000 clinical research studies and 5,000 researchers and staff, the Feinstein Institutes raises the standard of medical innovation through its five institutes of behavioral science, bioelectronic medicine, cancer, health innovations and outcomes, and molecular medicine. We make breakthroughs in genetics, oncology, brain research, mental health, autoimmunity, and are the global scientific leader in bioelectronic medicine a new field of science that has the potential to revolutionize medicine. For more information about how we produce knowledge to cure disease, visit http://feinstein.northwell.edu and follow us on LinkedIn.

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Study Supports Bioelectronic Medicine to Treat Rheumatoid Arthritis - Business Wire

Im no doctor! Im a bloody actor, ok?!

Anyone who lived in New Zealand and owned a TV in the 90s and early 2000s will be familiar with Claire Chitham or perhaps more likely her Shortland Street character Waverley Wilson, who she played from the age of 16.

From cancer scares to her marriage to Nick Harrison, we watched Waverley grow up and saw her through many dramas.

What most of us didnt know was behind the scenes, Chitham was having her own real life health battle. When she was 13, she was diagnosed with Crohns, a chronic inflammatory bowel disease, after suffering severe cramps which led to anaemia and drastic weight loss.

READ MORE:* What makes Fresh Eggs' Claire Chitham tick* Claire Chitham: 'Every time I ate I would be in pain'* Watch: Claire Chitham recalls her time on Shortland Street as Waverley

LAWRENCE SMITH

I was aware of was that I was so upset and stressed about certain things that I needed to be really careful that it didnt make me sick, Chitham says.

By her early twenties, Chitham, who has described herself as a Coca-Cola-drinking, afternoon-sugar-eating takeaway queen who smoked and didnt really do any exercise at that age, was paying less attention to her health and more to partying and her relentless acting role which all came crashing down when she found herself back in hospital with life-threatening levels of inflammation and the high possibility of requiring surgery to remove part of her bowel.

Chithams close call left her determined to get her health back on track and keep it that way.

And now, at 42, she is well versed when it comes to illness and wellness.

So much so that she and journalist friend Kylie Bailey have written a book, Good For You; a companion for Good For You TV, an online health and happiness hub the pair launched in 2016.

The book documents both womens health journeys and what theyve learned along the way, advocating an approach that recognises both conventional western medicine as well as alternative methods.

The intention was to create something like a coffee table book that you want to have sitting around it's not the kind of thing thats been designed to be read from cover to cover, Chitham says.

supplied

Karl Burnett and Claire Chitham starred together on Shortland Street. Chitham was just 16 when she got the role.

You might have a read of our stories, and then theres a collection of science-y things that we hope can gently educate people on how the body works, systems of the body and gut.

The second half of the book is all these tips and tricks and ideas that weve followed in our lives to try to either reach or maintain or work our way back to a place of good health.

Its not just telling a story for the sake of it, says Chitham.

I really want people to start viewing their health as something thats fun to engage with and doesn't have to be a chore.

I've been in a position before where that felt like a really big responsibility and too overwhelming and too much work, and we already have a lot going on in our lives, so I really understand how people can get frustrated and exhausted at the idea of trying to look after themselves.

LAWRENCE SMITH

I really want people to start viewing their health as something thats fun to engage with and doesn't have to be a chore.

For Chitham, this includes the ups and downs of acting life, going through a divorce in the public eye, dealing with her fathers dementia (which she writes about in the book) and of course, like the rest of us, adjusting to life in a global pandemic.

At those times I knew that I needed to deal with any emotional stuff as well, because I don't think your body will fully, properly heal if youve still got these things stored in you, she says.

For me I guess I had the benefit of being an actor I'm not scared of my emotions.

Ive been exploring and curious about my emotions from a young age and that's something in my toolbox of being an actor I have packed to explore and get to know.

So I'm aware of why I feel the way I do about things but it doesn't stop the feelings!

So things like going through my divorce and the things I speak about in the book with regards to my dad and his illness and my relationship with my family The thing I was aware of was that I was so upset and stressed... that I needed to be really careful that it didnt make me sick.

I guess that's my version of self-care. So I was actually being more careful with my physical health and making sure that I was exercising, making sure I wasn't eating s*** and that I was putting good stuff in and supplementing my body at that time, because I needed my health.

Chithams approach, and her advice to others, is to start small, doing small things you know will improve your health not just your physical health but mental, spiritual and emotional health too.

Instead of thinking you have to give up everything in your life, just try substituting one little thing a week or a month, whatever you can handle, where you actually feel like youre doing some good for yourself, she says.

And particularly when it comes to that spiritual stuff; Chitham knows its not everyones cup of tea, but stresses its all about finding balance.

I'm really aware of that in fact I have a goal of trying to take the woo woo out of wellness, she says.

I do think when youre chronically ill though, you get to a point where youre willing to try anything.

In her book, she writes: I have been given herbs and potions that made me want to puke. I have taken tiny pills in weird bottles that made me feel like I was invoking spirits.

I have had electro-magnetic bulbs moved up and down my body to balance my electrical charge.

I have had crystals and wands and heat lamps waved at me, needles stuck inside me, and hands moving energy in, on, and around me.

But Im also big on the fact that I needed my gastroenterologist and I needed the drugs to get to a point in my life where I wasnt in pain and when my pain and inflammation was managed and it was only then that I could start to even think about alternative therapies, she says.

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Claire Chitham: 'When you're chronically ill, you get to a point where you're willing to try anything' - Stuff.co.nz

It has been said that happiness is all about increasing pleasure and limiting pain. As such, pain is a pressing issue in many peoples lives. Whether chronic (lasting years) or acute (often stemming from a recent trauma), pain can be debilitating. Due to this nature, millions of Americans and others find themselves relying on opiates.

However, research is finding alternatives. Following up on 2018 research that found that cannabinoids may increase patients pain threshold while also making pain seem less unpleasant, a December 2020 meta-analysis comprehensively reviewed the available medical literature on cannabinoids and acute pain.

Photo by Anupong Thongchan/EyeEm/Getty Images

After searching through the available data, the analysis selected six studies. Of these six studies, 2 were American, 2 were Canadian, 1 was British, and 1 featured contributions from Germany, Italy, and the United Kingdom. Five of them studied orally administered cannabinoids, while one studied the effects of intramuscular cannabinoids.

Throughout the research, the group given orally administered cannabinoids did not differ significantly from the controls, who were given a placebo yet, the intramuscular patients saw a significant improvement in acute pain.

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The analysis went on to posit that this may be due to the differences in the metabolization of cannabinoids administered in various ways: Specifically, oral absorption of cannabinoids is slow and variable with maximal plasma concentrations occurring 60120 min post-ingestion but can be delayed upward of 6 h. Cannabinoids are subjective to significant first-pass liver metabolism, which further reduces the bioavailability. Utilizing transdermal, inhaled, or oral transmucosal formulations allows for direct plasma uptake and avoidance of the first-pass effect. Inhaled cannabinoids reach peak effect in 10 min and plasma levels are maintained for several hours.

Here, the available data seems to suggest that alternative methods to traditional oral consumption methods may be more effective at treating pain. Water-soluble oral administered cannabis may also be an adequate alternative as it also has a faster activation time. However, cannabinoid-based treatments did increase the presence of nonserious adverse effects. It did not increase the presence of severe adverse effects, which maintains its potential as a novel treatment method for acute pain.

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The study concludes by noting all of the studies were focused, if not solely based, on THC. While THC has a strong potential as a pain reliever, CBD is also a viable research candidate for novel treatment methods. Competitive and varied markets are fertile environments, and so expanding and exploring cannabis as a medicine will only enrich science and empower the consumer.

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Intramuscular Or Smoked Cannabis May Be The Future Of Managing Acute Pain - The Fresh Toast