Mark Witten

Using predictive biomarkers could improve success rate of new cancer drugs: U of T study

Christopher.Sorensen — Tue, 23 Feb 2021 17:49:41 +0000

Using predictive biomarkers could improve success rate of new cancer drugs: U of T study

Christopher.Sorensen Tue, 02/23/2021 - 12:49

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A new study by U of T Mississauga's Jayson Parker provides offers systematic, statistical evidence that biomarkers dramatically improve outcomes when it comes to testing new cancer medicines (photo by National Cancer Institute)

Mark Witten

Topic

Breaking Research

Biology

Cancer

Research & Innovation

U of T Mississauga

In recent decades, researchers have made big advances in developing new cancer medicines such as Herceptin, the targeted drug to treat women diagnosed with HER2-positive breast cancer. Yet, despite these successes, cancer remains the second leading cause of death after heart disease and nearly 90 per cent of all cancer drugs entering clinical trial testing fail.

Given the millions of lives at stake and the enormous size of the US$200-billion global oncology drug market, the ��߲ݴ�ý’s Jayson Parker asked a simple, but all-important question: “Is there a way to improve clinical trial failure risk?”

To find an answer, Parker, an associate professor, teaching stream, of biology at U of T Mississauga, launched a large-scale research project seven years ago to determine whether the use of predictive biomarkers – which help assess a patient’s likely response to a particular treatment – improved the odds that a new cancer drug would be approved in clinical trials conducted over the past two decades.

“We know the high failure rate isn’t because the medicines being tested aren’t working,” says Parker, who is also associate director for the master of biotechnology program at U of T Mississauga. “We wanted to see if biomarkers improved success rates.”

Now, in a recent study published in the journal Cancer Medicine, Parker and his co-authors provide the first systematic statistical evidence that biomarkers dramatically improve oncology outcomes when it comes to testing new medicines.

The new research compared drug approval success rates in biomarker-based clinical trials to outcomes in trials without biomarkers for four types of cancer: breast cancer, melanoma, non-small cell lung cancer and colorectal cancer.

“Our overall analysis of these four cancers showed drugs tested in biomarker-based trials were almost five times more likely to receive regulatory approval,” Parker says. “The evidence strongly supports using biomarkers to improve testing outcomes with new cancer medicines.”

The greatest benefit was seen in testing new drugs for breast cancer, where biomarker-based trials were 12 times more likely to succeed. There was an eightfold increase in success rates for melanoma drugs that used biomarkers and a sevenfold increase for lung cancer medicines. While drugs for colorectal cancer showed no overall benefit, the researchers say this could change in the future as more biomarkers for colorectal cancer are introduced.

Parker evaluated the performance of both well-established and new, exploratory biomarkers. The study’s second key finding revealed that using new biomarkers before they had been properly validated also improved success rates in oncology clinical trials. That is surprising and encouraging, according to Parker, because some experts thought the use of new, unproven biomarkers could potentially increase failure risk.

“The data showed exploratory biomarkers still conferred a fourfold benefit compared to no biomarkers. This suggests drug developers can take a chance on new biomarkers because the broad benefits of biomarkers are so strong,” he says.

A pre-COVID photo of some of the students involved in the study. From right: Rohan Tangri, Ashini Weerasinghe, Zain Shah, Kirill Pereverzev and Stephen Mac.

Parker’s paper started as a U of T Mississauga Research Opportunity Program project in 2014. Seven students have been involved, including four from the MBiotech Program, and they collaborated with an oncologist, computer scientist and data scientist.

Data scientist Nicholas Mitsakakis applied an innovative machine-learning statistical method, known as multi-state Markov modelling, to analyze 20 years of multi-phase clinical trial data.

“It was challenging, but exciting to use this method for the first time in an application for cancer drug testing,” says Mitsakakis, who teaches data science in the MBiotech program and is an adjunct lecturer in biostatistics at U of T’s Dalla Lana School of Public Health. “The data set was a gold mine.”

The study’s robust statistical analysis supports early and aggressive adoption of biomarkers in the design of oncology clinical trials. These new findings matter because oncologists will be more likely to encourage their patients to participate in drug trials that use biomarkers. For the pharmaceutical industry, wider use of biomarkers could reduce drug development costs through better outcomes and the weight of the evidence could help overcome hesitancy or reluctance to use biomarkers because they target sub-populations of patients.

Precision medicine is about choosing the right drug for the right group of patients, says Parker, and Biomarkers are a critical tool in precision medicine with the potential to substantially improve success rates in cancer drug development and treatment.

“The goal is to get more new cancer medicines approved and medicines that work better in a field with a high risk of failure,” he says. “Using biomarkers in designing clinical trials is a win-win for drug manufacturers, insurers, oncologists and for patients.

“The only excuse now for conducting a clinical trial without a biomarker is if there is none available.”

The kids are gonna be alright

sgupta — Thu, 16 May 2013 14:58:10 +0000

The kids are gonna be alright sgupta Thu, 05/16/2013 - 10:58

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U of T's new program in child and adolescent psychiatry seeks to help youth such as Nick Carveth (photo by Geoff George)

Mark Witten

Author legacy

Mark Witten

More News

Medicine

Subheadline

U of T offers help for children and youth with mental health issues

Nick Carveth was paralyzed by anxiety in his large high school classes. Although bright and articulate, the lanky teen didn’t dare speak up for fear his peers would judge him.

Smoking weed helped calm his nerves but before long Carveth was chasing his stress away with chemical drugs such as ecstasy. By age 16, he was carrying a crack pipe in his leather jacket, smoking it just to get through the day.

“My drug use was off the charts,” says Carveth, shaking loose a mass of dreadlocks tucked inside a hemp-coloured tam. He tried a handful of abstinence-based drug programs, but they didn’t address his mounting social anxiety and, by age 17, he’d been expelled from two different schools.

“I felt alone, like my problems were a life sentence, and there was no way out.”

Sadly, Carveth’s struggles are common. Psychiatric disorders are now the number-one reason young people in Canada are hospitalized and why suicide is second only to car accidents as the leading cause of death. Recent high-profile media tragedies involving mentally ill teens — from the suicide of bullied B.C. teenager Amanda Todd to the Christmastime massacre at Sandy Hook — are evidence of the devastation that can happen when kids don’t get the help they need.

“Families and youth in crisis often don’t know where to turn. Navigating Ontario’s complex and fragmented youth mental health care system can be daunting. We want to facilitate youth getting the right care at the right time in the right place,” says Corine Carlisle, a professor in the ��߲ݴ�ý’s Department of Psychiatry. “We need to intervene earlier and follow up faster to get youth back on an optimal developmental trajectory. We especially want to provide timely, efficient care so that crises don’t become fatal.”

Identifying and treating mental illness early is a critical part of U of T Medicine’s strategy for improving youth mental health. From backing leading-edge research to developing new, team-based treatment models, the Faculty is helping to ensure teens like Carveth can live meaningful, productive lives — while also reducing the staggering costs to the health care system resulting from disabling, lifelong mental health problems.

Training more experts in youth mental health is key. Recently, the Department of Psychiatry introduced a new subspecialty program in child and adolescent psychiatry.

“We felt strongly there was a need to focus on underserved areas of psychiatry. The new subspecialty training will increase the number of specialists in child and adolescent psychiatry, making it easier for troubled kids to get the help they need,” says Department Chair Trevor Young, noting that historically mental health has been a stigmatized area of medicine and child psychiatry even more so a “poor cousin” within the field.

During a two-year program, trainees will serve as consultants to schools, correctional programs, family health teams and community-based children’s mental health agencies, treating kids with mental health problems together with other health professionals. Some of their training will be spent caring for young people with the most complex and difficult problems — such as concurrent substance abuse and mental illness issues — like Carveth’s.

But simply training more psychiatric experts is not enough. Research has shown that kids benefit from coordinated care between teams of health professionals — from emergency room staff to family doctors and child psychiatrists. That’s why U of T, the Centre for Addiction and Mental Health (CAMH) and The Hospital for Sick Children teamed up to form an integrated Child and Youth Mental Health program.

The program will help provide more coordinated care for kids with mental illness by integrating child psychiatrists into mixed treatment teams committed to working together, including family physicians, nurse practitioners and other professionals.

It will also ensure that scientific research, psychiatric training and clinical care are properly coordinated. Professor Peter Szatmari, director of U of T’s Division of Child and Adolescent Psychiatry who will lead the program, says this structure — where information, expertise and resources are shared — will be critical in tackling the growing needs of children, youth and their families.

“One in five children and youth has a mental health problem and only 15 per cent of them receive help from a mental health professional. There’s a huge gap between the need and access to these services,” says Szatmari, chief of the Child and Youth Mental Health Collaborative at the two hospitals. “I see myself as a matchmaker to bring some of the best minds in the field together with a common focus and vision, and come up with solutions. I don’t see child psychiatrists in private practice as a model for today.”

That’s why Szatmari plans to build on the joint program with CAMH and SickKids by setting up partnerships with U of T and other children’s mental health agencies and hospitals affiliated with the Department of Psychiatry.

Ramping up research is another priority, says Szatmari, because it identifies weak spots in the system and areas where future efforts should be focused. “A primary goal is to increase research productivity, mentoring the best and brightest so they can be more successful,” says Szatmari, also the director of Research and Training in child and youth psychiatry at U of T.

A good example is recent research by Carlisle, which found that follow-up care for Ontario teens with psychiatric issues is not optimal: less than half of young people aged 15 to 19 hospitalized with a psychiatric diagnosis received follow-up care within a month of being discharged.

“Timely aftercare is crucial in maintaining the health of youth with mental illness and avoids future hospitalization,” says Carlisle, the dynamic clinical head of CAMH’s Youth Addiction and Concurrent Disorders Service.

Coordinated care is especially critical for youth suffering from multiple issues, which is why, last July, CAMH opened a new inpatient unit offering 24-hour care for young people with concurrent disorders. The first program of its kind in Canada, the 12-bed unit — headed by Carlisle — will treat up to 150 youth from across the province each year.

“If you treat substance abuse and mental health issues together, the success rate is much higher,” Carlisle says, noting that of the first 20 youth to complete the program, only one so far has required readmission. “Our inter-professional team is phenomenal at engaging with these youth. These young people come here having given up on themselves. They feel their families, the schools and the justice system have given up on them too. It’s really powerful to see them turn their lives around and regain hope for the future.”

For Carveth, it was an outpatient day-treatment program specially designed for teens with mental health and substance abuse problems that helped him regain control over his life. The REACH (Recovery and Education for Adolescents Choosing Health) program, offered by CAMH and the Toronto District School Board, is a harm-reduction program that allows students to work toward high school credits while receiving treatment.

“The counsellors are so friendly and empathetic. They meet you where you are at the moment and you get to set your own goals, which helped build momentum in my recovery,” says Carveth, who thrived as part of a small group of six students. The program helped him understand how his drug use was a way of coping with anxiety and an undiagnosed obsessive-compulsive disorder.

Thanks to REACH, Carveth dropped his crack cocaine habit, learned to manage his anxiety symptoms and graduated from high school as an Ontario Scholar. Now 23, he’s finishing his third year in the Bachelor of Social Work program at Ryerson University, and passionately interested in counselling youth with mental illness and addictions.

“I got the help I needed to face and overcome these issues. That’s given me a career path and an opportunity to help others, one of the most spiritual things in life,” he says.

Check out this story and more in the Spring 2013 issue of U of T Medicine Magazine.

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War wounds: the struggle of Mexican journalists

sgupta — Tue, 23 Apr 2013 09:46:29 +0000

War wounds: the struggle of Mexican journalists sgupta Tue, 04/23/2013 - 05:46

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Journalists protest the murders and kidnappings of their colleagues in Mexico leaving photos outside the Ministry of the Interior (all photos courtesy Knight Foundation via Flickr)

Mark Witten

Author legacy

Mark Witten

Topic

Subheadline

Threats, violence and murder by drug cartels

Over the past decade, ��߲ݴ�ý psychiatry professor Anthony Feinstein has interviewed hundreds of international war correspondents to assess their mental health.

Still, nothing prepared him for the gruesome tales he heard from Mexican journalists about drug-related bloodshed on home soil.

“It’s a very violent environment. Tens of thousands of Mexicans have died, and the cartels have silenced many journalists through murder and intimidation,” says Feinstein, who is also director of the Neuropsychiatry Program at Sunnybrook Health Sciences Centre.

Mexico is widely considered one of the most dangerous countries in the world to practice journalism. Last year, more than 170 writers around the world, incuding Neil Gaiman, Margaret Atwood, Chinua Achebe, Colm Toibin and Toni Morrison signed an open letter to the journalists and writers of Mexico "calling out for the killing, the impunity, the intimidation to stop". And Renu Mandhane, director of the Faculty of Law's International Human Rights Program travelled to Mexico as part of an international delegation led by John Ralston Saul asking the government to uphold its legal responsibilities to protect journalists. (Read Mandane's account of the experience.)

In the first study of its kind, Feinstein found that Mexican reporters covering drug trafficking have as much or more mental distress than war journalists. One in four journalists suffers from mental health problems. Almost half the journalists surveyed know of a colleague murdered by drug cartels and it is not uncommon for reporters' families to be threatened or injured.

“They can’t escape the conflict, unlike war correspondents who can get a break,” says Feinstein, whose previous research changed the way big news organizations prepare and care for war correspondents.

After revealing that war journalists had rates of posttraumatic stress disorder and depression far exceeding that of the general population, CNN asked Feinstein to lead newsroom educational sessions for journalists about to be deployed and help provide counselling for people returning from the field. He has also helped the BBC, Reuters, CBC, and the Globe and Mail.

His website, www.conflict-study.com, is a resource for journalists suffering from work-related trauma.

But Feinstein hasn’t yet persuaded Mexican news organizations to act.

“It’s going to be very challenging to convince them to take this issue more seriously,” he says, adding it’s his fervent hope that Mexican journalists get the help they so desperately need.

See more stories from Medicine in the latest issue of U of T Medicine Magazine.

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