‘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

Just Posted

The Aquatic Centre at Western Financial Place.
Cranbrook Aquatic Center to close temporarily

The annual shutdown of the Aquatic Center at Western Financial Place will begin earlier than scheduled this year and does not have a defined end date at this time.

The latest EKASS survey confirms a steady decline in substance use among EK youth over the years. (image compilation via Pixabay)
Latest survey shows steady decline in adolescent substance use over the years

Starting in 2002, the survey has been conducted every two years to monitor changes in substance use patterns, attitudes and behaviors amongst East Kootenay youth.

The ‘official’ opening of 2nd Edition Coworking in downtown Fernie, a project five years in the making by the Fernie Chamber of Commerce. Left to right: Executive Director of the Fernie Chamber Brad Parsell, incoming President of the Fernie Chamber Norm Fraser, outgoing President of the Fernie Chamber Anita Palmer, and Mayor of Fernie Ange Qualizza. (Scott Tibballs / The Free Press)
Fernie Chamber cuts the ribbon on 2nd Edition

The new coworking space in Fernie is now ‘officially’ open, but has been operating since early 2021

Residents line up outside the Vernon Recreation Complex for their COVID-19 vaccine Saturday, June 5. (Jennifer Smith - Morning Star)
No appointments necessary for first dose COVID-19 vaccine: Interior Health

People can just show up at clinics, register on the spot and get the shot

Sparwood Mayor David Wilks with the new AED SaveStation installed at the Sparwood Leisure Centre. (Contributed by District of Sparwood)
Sparwood installs public AED

The SaveStation was installed thanks to a grant from CP Rail

Canadian Prime Minister Justin Trudeau participates in a plenary session at the G7 Summit in Carbis Bay, England on Friday June 11, 2021. THE CANADIAN PRESS/Adrian Wyld
Canada donating 13M surplus COVID-19 vaccine doses to poor countries

Trudeau says the government will pay for 87 million shots to be distributed to poor countries

Highway notices like this come down effective June 14. Public health restrictions on non-essential travel and commercial operation have hit local businesses in every corner of B.C. (B.C. government)
Province-wide travel back on in B.C.’s COVID-19 restart plan

Gathering changes include up to 50 people for outdoor events

Calgary Stampeders’ Jerome Messam leaps over a tackle during second half CFL western semifinal football action in Calgary, Sunday, Nov. 15, 2015.THE CANADIAN PRESS/Jeff McIntosh
CFL football will be played this summer in Canada

Governors vote unanimously in favour to start the ‘21 campaign on Aug. 5

Cannabis bought in British Columbia (Ashley Wadhwani/Black Press Media)
Is it time to start thinking about greener ways to package cannabis?

Packaging suppliers are still figuring eco-friendly and affordable packaging options that fit the mandates of Cannabis Regulations

Citizenship Minister Marco Mendicino holds a press conference in Ottawa on Thursday, Nov. 12, 2020. The federal government is announcing that Indigenous people can now apply to reclaim their names on passports and other government documents. THE CANADIAN PRESS/Sean Kilpatrick
Indigenous people can now reclaim traditional names on their passports and other ID

Announcement applies to all individuals of First Nations, Inuit and Métis background

Harvesting hay in the Fraser Valley. (Tom Fletcher/Black Press)
COVID-19: B.C. waives farm income requirement for a second year

Property owners don’t need minimum income for 2022 taxes

Cruise ship passengers arrive at Juneau, Alaska in 2018. Cruise lines have begun booking passengers for trips from Seattle to Alaska as early as this July, bypassing B.C. ports that are not allowed to have visitors until March 2022 under a Canadian COVID-19 restrictions. (Michael Penn/Juneau Empire)
B.C. doesn’t depend on U.S. law to attract cruise ships, Horgan says

Provinces to get update next week on Canada’s border closure

This undated photo provided by Girl Scouts of New Mexico Trails shows a scout donating cookies to firefighters in Rio Rancho, New Mexico, as part of the Hometown Heroes program. As the coronavirus pandemic wore into the spring selling season, many Girl Scout troops nixed their traditional cookie booths for safety reasons. That resulted in millions of boxes of unsold cookies. (Girl Scouts of New Mexico Trails via AP)
Thinner Mints: Girl Scouts have millions of unsold cookies

Since majority of cookies are sold in-person, pandemic made the shortfall expected

In this artist’s sketch, Nathaniel Veltman makes a video court appearance in London, Ont., on June 10, 2021 as Justice of the Peace Robert Seneshen (top left) and lawyer Alayna Jay look on. THE CANADIAN PRESS/Alexandra Newbould
Terror charges laid against London attack suspect

Crown says Nathaniel Veltman’s four counts of first-degree murder constitute an act of terrorism

Most Read