‘Planning for dropouts’: Drugmakers grapple with testing unproven vaccines on seniors

Seniors, by far, have been hardest hit by the novel coronavirus

Retired nurse Donna Lessard is shown in a recent handout photo provided by Lessard. THE CANADIAN PRESS/HO-Donna Lessard MANDATORY CREDIT

Retired nurse Donna Lessard is shown in a recent handout photo provided by Lessard. THE CANADIAN PRESS/HO-Donna Lessard MANDATORY CREDIT

At age 70, retired nurse Donna Lessard can expect to be towards the front of the line for a COVID-19 vaccine when supply and distribution expands in coming months.

But instead, she’s opted for an unproven vaccine candidate she can have now – a two-dose product by the Quebec City-based biopharmaceuticalMedicago currently running Phase 2 clinical trials.

Because the trials are blinded, the Montrealer doesn’t know if last month she received a second dose of the prospective vaccine or a placebo, and may not know for a year – well after most Canadians are expected to receive one of several licensed vaccines.

Lessard admits her decision could put her at risk of COVID-19 infection much longer than other seniors, but says there are many people who need approved vaccines more urgently than she does.

“I’m not in a nursing home, I’m in excellent health,” says Lessard, who was a nurse for 50 years before retiring in 2020. “There are a lot of other people, rightly so, that would go before me.”

Despite the willingness of senior trial participants like Lessard, whether and how to include seniors in COVID-19 vaccine trials poses thorny ethical questions now that effective vaccines are available and more are soon to come, says University of Toronto bioethicist Kerry Bowman.

Seniors, by far, have been hardest hit by the novel coronavirus, with about 70 per cent of Canada’s COVID-19 deaths involving people aged 80 and older, and nearly 20 per cent between the ages of 70 and 80.

The emergence of more infectious variants adds even more uncertainty to the pandemic, especially after one version was linked to a devastating outbreak that engulfed a Barrie, Ont., long-term care facility and killed dozens of residents.

“I generally don’t think it’s justifiable right now having senior citizens in completely blinded trials,” says Bowman.

“We can’t fully quantify risks, which I think is significant…. The variants are the wild card now. We don’t even know which way this is going and the whole situation could get a lot worse very quickly.”

Still, there can be exceptions for healthy volunteers such as Lessard, especially if the trial is designed to minimize potential harms, Bowman allows.

The Medicago trial limits its use of placebos as one way to do that – the company says that for every volunteer who gets a saline injection, five participants receive the proposed vaccine.

That’s instead of splitting volunteers equally between the placebo and treatment groups, more typical in double-blinded trials trying to assess how effective a proposed drug really is.

Given the risks posed by the ongoing pandemic, infectious disease physician Zain Chagla suggests it would more appropriate to compare vaccine hopefuls to already proven options, which in Canada are by Pfizer-BioNTech and Moderna.

It’s hard for researchers to say they’re not causing harm if they effectively deny someone a proven drug, says Chagla, an associate professor of medicine at McMaster University in Hamilton.

“Many of these trials will have to eventually have some implementation of a standard-of-care drug, which might be Pfizer,” Chagla says of placebo arms.

“And then at the end, make sure that everyone who got the (tested) drug also gets Pfizer,” says Chagla, adding the caveat that there are still uncertainties about what happens when someone takes two different COVID-19 vaccines.

All clinical trials undergo multiple ethics and protocol reviews by the drug developer and Health Canada to ensure patient safety remains paramount, says Karri Venn, president of research at LMC Manna Research, which is running multiple trials for various biotechs, including Medicago’s vaccine trial.

And trials don’t typically start with seniors or other vulnerable groups. Only if Phase 1 establishes safety among healthy adults would studies expand to older volunteers, with later trials adding in adolescents, children and pregnant women.

Venn says COVID-19 has added novel complications to scientific research, and suspects it could soon become difficult to recruit and keep seniors committed to clinical trials if they know an approved vaccine is imminent.

“This is for the first time posing a lot of challenges for the traditional way in how you would do research, to be honest with you,” says Venn, expecting some volunteers sign up planning to quit as soon as they’re eligible for other, approved options.

“They may say, ‘I’m going to take (this proposed vaccine) and in nine months I’m going to say, “You know what? Unblind me.”’ … There’s all of that happening, too. It’s a very unusual time.”

It’s very rare to unblind a participant partway through a trial, Venn adds, and if it does happen, it’s almost always for a medical or safety reason.

But all trials must release any participant who wants to quit, no matter the reason, she says, and their data wouldn’t be included in the final results.

Giving seniors a placebo is out of the question for Providence Therapeutics CEO Brad Sorenson, who is planning Phase 2 trials for his COVID-19 vaccine hopeful.

The head of the Calgary-based biotech says his recently launched Phase 1 safety trials include a placebo group, but no seniors. Phase 2 will likely include seniors but no placebos.

“We don’t want to include a placebo group for people that are older and at a higher risk. Not when there’s a vaccine that would be available to them,” says Sorenson, musing on a possible workaround.

“We can do a comparative study where they get either our vaccine or a Moderna vaccine.”

Assuming the trial can get its hands on these approved vaccines – allotments from Moderna and Pfizer are both facing significant distribution delays in Canada.

Bowman sympathizes with volunteers who consider unknown protections of a trial vaccine to be better than nothing. He suggests those who consent to the terms of clinical trials do so “under duress.”

“Before Christmas, we were told we’d be swimming in vaccines by now, and we’re really, really not,” says Bowman.

“People have to protect their own lives and well-being.”

READ MORE: Trudeau says government foresaw short-term delays in vaccine deliveries to Canada, planned accordingly

Still, concrete data on how seniors respond to prospective COVID-19 vaccines is crucial, especially with relatively few therapies and so much still uncertain about the disease, says Medicago’s senior director of scientific and medical affairs.

“I know it’s a big request, but it’s part of science and that’s how it works and that’s how we make sure the product is good, that the people receiving it are safe,” says Nathalie Charland.

“There are constraints related to the trial, we are aware of that, and that’s why we say a big thank you to all those who are involved in our trials.”

Charland says Medicago’s Phase 2 trial has already collected the data it needs from hundreds of senior volunteers in Canada and the United States, but recruiting the thousands more needed in Phase 3 will be tougher.

Half of the 30,000 participants needed are seniors, and half of all volunteers would get a placebo, she says.

“We are already planning for dropouts. We are very conscious that this might – and probably will – happen but Phase 3 is an efficacy trial so we have to go in regions of the world where the virus is circulating a lot,” she says, noting prospective sites include Latin America and Europe.

“It will be in countries where there’s not that many vaccines distributed yet. So that should help recruit subjects.”

Lessard suspects she got Medicago’s vaccine candidate, citing a slight headache and sore arm after the first dose and another sore arm after the second dose.

But she says that was not her primary reason for joining the trial, expressing hope her involvement will serve a greater public good.

“There’s a lot of fear around the COVID vaccines and we still hear people saying, ‘Oh, I’m not going to take the vaccine until it’s perfect,’” says Lessard.

“And my attitude is: Well, how are we going to get it perfect if nobody volunteers? And if not now, when? It’s got to be done now.”

Cassandra Szklarski, The Canadian Press


Like us on Facebook and follow us on Twitter.

Want to support local journalism during the pandemic? Make a donation here.

CoronavirusSeniorsvaccines

Get local stories you won't find anywhere else right to your inbox.
Sign up here

Just Posted

(Pacific Coastal Airlines photo)
Potential COVID-19 exposure on March 1 Penticton flight

Interior Health lists a public exposure for the Pacific Air Flight from Vancouver on March 1

The Town of Osoyoos is looking into allowing two food trucks at the downtown plaza over the summer, which would require updates to several town policies and bylaws. (Kevin Clark - Black Press Media File)
Osoyoos council to weigh allowing additional downtown food trucks

The proposal would be aimed to benefits the summer’s downtown plaza

Seniors in the Interior Health region can book their COVID-19 vaccinations starting Monday, March 8, 2021 at 7 a.m. (File photo)
Seniors in Interior Heath region can book COVID-19 shots starting Monday

Starting March 8 the vaccination call centre will be open 7 a.m. to 7 p.m. daily

(Baldy Mountain Resort / Facebook) 
(Baldy Mountain Resort / Facebook)
Baldy Mountain calls out snowmobilers for damaging ski hill

The Resort is fed up with snowmobilers running across their trails

C.E. “Ned” Bentley owned a garage on Shaughnessy Avenue, now Lakeshore Drive in Summerland. Bentley later went on to serve on Summerland’s council and was recognized with the Good Citizen Award in 1939. (Summerland Museum photo)
Former Summerland reeve once ran garage

C.E. “Ned” Bentley was a prominent figure in Summerland’s past.

The James C Richardson Pipe Band marches in a Remembrance Day parade on Nov. 11, 2019 in Chilliwack. Wednesday, March 10 is International Bagpipe Day. (Jenna Hauck/ Chilliwack Progress file)
Unofficial holidays: Here’s what people are celebrating for the week of March 7 to 13

International Bagpipe Day, Wash Your Nose Day and Kidney Day are all coming up this week

Multiple people were injured at a Vernon home following an early-morning break-in Saturday, March 6, 2021. (Black Press file photo)
Multiple people left injured following break-and-enter in Vernon

Police believe the early-morning break-in was targeted and not a threat to the general public

Kelowna General Hospital (File photo)
Second COVID-19 outbreak declared at Kelowna General Hospital

One patient and one staff member on Unit have tested positive for the virus.

Victoria man Brett Andersen is asking for people’s help to secure him one of eight free tickets to the moon. (Screenshot/@brettandersen Instagram)
Victoria man wants your help securing a free ticket to the moon

Japanese billionaire offering eight people a trip to the moon

The Conservation Officers Service is warning aquarium users after invasive and potentially destructive mussels were found in moss balls from a pet store. (BC Conservation Officers Service/Facebook)
Aquarium users in B.C. warned after invasive mussels found at pet store

Conservation officers were told the mussels were found in a moss ball from a Terrace pet store.

A Coldstream resident who found an owl struggling on her property in March 2021 is now spreading awareness of about the knock-on effects of rodent poisoning. (Kathy Renaud photo)
Okanagan owl ‘fighting for her life’ after ingesting rat poison

Coldstream resident warns against the use of rodenticide due to risk of secondary poisoning in raptors

Hockey hall-of-fame legend Wayne Gretzky, right, watches the casket of his father, Walter Gretzky, as it is carried from the church during a funeral service in Brantford, Ont., Saturday, March 6, 2021. HE CANADIAN PRESS/Nathan Denette
Walter Gretzky remembered as a man with a ‘heart of gold’ at funeral

The famous hockey father died Thursday at age 82 after battling Parkinson’s disease

Fire ripped through a mobile home on Boucherie Road in West Kelowna on March. 6. (Phil McLachlan - West Kelowna News)
‘My whole life just went up in smoke’; Fire consumes Okanagan mobile home

RCMP confirmed that there were no injuries due to the fire

Most Read