By KELLY GRANT
Friday, December 14, 2018
Before the Canadian experts who weigh the merits and costs of pharmaceuticals consider recommending public funding for a new drug, they ask patient-advocacy groups to share their thoughts in writing.
The patient groups who take part in this process range from tiny, volunteer-run outfits focusing on rare diseases to large national charities with familiar names such as the Arthritis Society and Diabetes Canada.
No matter their size or influence, the groups tend to have one thing in common: They receive money from the same pharmaceutical companies whose drugs are up for consideration at the little-known Canadian Agency for Drugs and Technologies in Health (CADTH), whose dense, technical evaluations can make or break a new drug's prospects in this country.
A Globe and Mail analysis has found that in 78 per cent of cases, the patient-advocacy groups making written submissions to the CADTH have a financial conflict of interest with the manufacturer of the drug under review.
The figure is even higher - 86 per cent - in cases where patient groups are commenting on new drugs for cancer.
Although the overwhelming majority of patient groups indicated to the CADTH that pharmaceutical companies had no role in their submissions, a handful disclosed that drug makers provided technical briefings, introduced them to patients who had tried the new drug or paid for the patient survey that underpinned their written comments.
The Globe's review of more than 400 submissions to the CADTH reveals how heavily these patient organizations rely on the pharmaceutical industry, which raises questions about the groups' freedom to speak out about the high prices and side effects of some prescription drugs.
Documenting the extent of the conflicts of interest is difficult because no level of government requires drug companies or patient groups to disclose the exact payments or how they were used.
However, at least 14 patient groups have over the past 15 months disclosed that they received more than $50,000 from one or more pharmaceutical companies after the CADTH began asking the groups to tick a box indicating a range of funding.
Despite calls from leading physicians and others for more transparency, Ontario's Progressive Conservative government has not enacted legislation passed by the previous, Liberal government that would have required drug companies to reveal all payments of more than $10 to patient groups, as well as to doctors, hospitals, universities and others.
"It's a huge problem," said Bryn Williams-Jones, director of the bioethics program at the University of Montreal's school of public health. "The problem is both in the functioning of these groups and their inability to be independent from industry."
The patient group leaders interviewed for this story - some of them disease survivors who built their organizations from scratch and still serve as volunteers - all said that drug makers have no say whatsoever in their policy positions.
Yet, many are also deeply ambivalent about asking the pharmaceutical industry to pay for their conferences, websites, patient-information booklets, awareness campaigns and, in some cases, operating costs. They know how it looks, but say they can't raise enough money to get by from individual donors or public sources.
In March, a coalition of seven cancer-patient groups, weary of being dismissed as shills for Big Pharma, sent letters to the federal Finance Minister and health ministers in Ottawa and every province asking for government funding.
"The impetus for this request is the ongoing criticism these groups receive for accepting funding for their work from the pharmaceutical industry," wrote Martine Elias, the executive director of Myeloma Canada and chairwoman of the coalition. "This is used as an excuse to ignore the input of these groups on health policy issues no matter the substance of their concerns or the fact that they receive their mandate to take their positions from their constituencies, especially their members."
So far, the federal and provincial governments have either dismissed their funding request or ignored the letter, Ms. Elias said.
The Globe's findings and the patient groups' own concerns raise wider questions about how patient-advocacy work should be funded in Canada, especially when health-care leaders are trying to give patients a more significant say in everything from setting research agendas to running hospitals.
Brian O'Rourke, president of the CADTH, said he was not surprised that financial conflicts of interest were present in more than three-quarters of all patientinput submissions on new drugs.
"In an ideal world, we'd like that number to be zero," Dr.
O'Rourke said. "We also understand that the patient groups do some fantastic work and to do that work they need some resources."
The CADTH is a crucial stop on the road to public funding for new drugs and medical devices.
It's not the first stop, however.
To be sold in Canada, prescription drugs must first be approved by Health Canada, which simply reviews the scientific evidence proffered by a manufacturer to determine if the benefits of a new medicine outweigh its risks.
Health Canada has no say on price. Another agency, the Patented Medicine Prices Review Board, sets ceiling prices for drugs. (The federal government is in the midst of a contentious regulatory overhaul aimed at lowering those ceilings.)
But neither Health Canada nor the pricing regulator pass judgment on whether a new drug is any better than what is already on the market or whether governments should cover it when they have so many competing demands on their health-care dollars.
This is where the CADTH comes in. Funded jointly by the federal government, provincial and territorial governments outside Quebec and fees from drug makers, the independent agency's expert panels publish recommendations about whether drugs should garner public funding. Often, they will recommend that a drug be covered but only for a narrow subset of patients - and only if the manufacturer slashes the price.
Although the recommendations are not binding, governments rarely break ranks with the CADTH. Usually, if the agency's experts advise against the public funding of a drug, patients cannot get the medication unless they have a generous private insurance plan or deep pockets.
Pharmaceutical companies, meanwhile, can't make nearly as much money off their drugs in Canada if governments refuse to cover them.
In 2010, the CADTH's Common Drug Review - the part of the agency that offers advice on noncancer drugs - began asking patient groups to submit written comments on the drugs it was preparing to review. Patient
groups were already offering their thoughts in writing on cancer drugs through another review process, called the pan-Canadian Oncology Drug Review, which came under the CADTH's umbrella in 2012.
The idea, Dr. O'Rourke said, was to hear from patients about what mattered to them in a new drug.
To cite one example, he said that when new biologic drugs became available for rheumatoid arthritis, some of the expert committee members were worried about potentially serious side effects, including an elevated risk for some cancers.
"We heard from patients, 'It's really challenging to live with this disease, and taking these biologics has given us our life back. ... We're willing to take that risk,' " Dr. O'Rourke said. "That's kind of an example of how it helped the expert committee understand some of the trade-offs [patients] were willing to make."
Patient input is just a small part of the overall review, which is mostly concerned with clinicaltrial evidence and a value-formoney assessment. But it's easy to see how drug companies, with so much potential profit at stake, would benefit from glowing reviews of their medications from patients who've received the drugs through clinical trials or compassionate-access programs paid for by the manufacturer.
In an effort to control for that influence, the Common Drug Review and the pan-Canadian Oncology Drug Review ask patient groups to disclose the names of the companies that fund them as part of their submissions.
That makes the CADTH website a rare central place to discover which companies are funding which patient groups.
The Globe reviewed the conflict-of-interest disclosures for every patient-group submission posted in full to the CADTH's website - 446 in all, 152 for cancer drugs and 294 for other kinds. In 349 cases - or 78 per cent of the total - the groups revealed they had received money from the maker of the drug under review.
In 97 instances, the groups did not declare that kind of direct financial conflict of interest. However, in many of those 97 cases, the groups disclosed receiving money from pharmaceutical companies other than the one whose drug was under consideration at the CADTH. (An exact figure is impossible to determine because of the ambiguous way the CADTH asks about conflicts of interest in one iteration of its form, which has changed over time.
Some groups only list conflicts with the maker of the drug under review, while others choose to list all their sources of pharmaceutical-industry funding.)
The drug companies whose names appeared most often in the disclosures were Janssen, which is a division of Johnson & Johnson, followed by Novartis, Pfizer, Merck, AbbVie and Roche.
The patient groups that made submissions most often were Arthritis Consumer Experts, a B.C.based non-profit for arthritis patients; the Canadian Liver Foundation; the Canadian Treatment Action Council, which advocates for HIV patients; Lung Cancer Canada; and the Canadian Skin Patient Alliance.
The Melanoma Network is another of the groups that frequently contribute to CADTH reviews.
Pharmaceutical money helped the fledgling organization get off the ground.
Annette Cyr founded the Melanoma Network in 2009, nine years after the first of her three bouts with the serious skin cancer, which killed an estimated 1,250 Canadians in 2017, according to the Canadian Cancer Society.
"We started with nothing," Ms.
Cyr said. "I put $25,000 of my own money into starting the organization. [At first,] we couldn't get any assistance from anybody."
Eventually, she said, she persuaded Merck to give her seed money to help build a website and expand her patient-support organization, which today has four paid employees working out of a small office in Oakville, Ont. Ms.
Cyr remains an unpaid volunteer and is grateful to the drug companies that cover between 20 per cent and 30 per cent of her organization's budget.
In one of the few cases in which a patient group acknowledged receiving direct funding for part of their CADTH submission, the Schizophrenia Society of Canada disclosed that the Canadian branch of Japanese drug maker Otsuka paid for the online patient survey that formed part of the society's 2017 submission on brexpiprazole, an antipsychotic sold under the brand name Rexulti. It is sold in Canada by Otsuka in partnership with Danish drug maker Lundbeck.
Chris Summerville, chief executive of the Schizophrenia Society of Canada, said an Otsuka representative told him the drug was to be reviewed by the CADTH and offered to pay for the online survey and analysis, which ultimately cost about $7,000.
But Mr. Summerville said the society drafted the questions for the survey and wrote the submission for the CADTH without any input from Otsuka, which a company spokesman confirmed by email. "We're not influenced by Otsuka or any pharmaceutical company," Mr. Summerville said.
"They all know this about Chris Summerville, okay? I will not sell my soul."
Mr. Summerville, an Alabamaborn former pastor whose immediate family has struggled with schizophrenia and bipolar disorder, said he is clear-eyed about why drug companies contribute to the society, which now receives about 15 per cent of its funding from two firms: Otsuka and Janssen.
"I think what safeguards me," he said, "is that I am aware they do have an agenda. They want their medication acknowledged, used and promoted."
In the past, he added, the society received funding from eight or nine different companies, but that dried up as other drugs for schizophrenia saw their patents - and their potential for profits - expire.
The opposite tends to happen when pharmaceutical companies prepare to launch new medications in Canada.
Companies sometimes seek out small patient groups and offer them financial support and help in amplifying their message - a tactic some patient advocates find distasteful.
Erin Little is one of those advocates. The 35-year-old from Port Elgin, Ont., is the mother of two girls, one of whom has an ultrarare inherited metabolic disorder called cystinosis. It is believed to affect fewer than 100 Canadians.
Left untreated, the disease causes an amino acid called cystine to flood the body and inflict lethal damage on organs, beginning with the kidneys. Ms. Little's older daughter, nine-year-old Olivia, has been managing her disease for almost seven years with an old drug called Cystagon, which is only available in Canada through a special program that allows patients to use prescription drugs that have not been approved by Health Canada. No company has applied to sell Cystagon in Canada because it would be difficult to turn a profit with so few patients.
All that changed last year, when Dublin-based Horizon Pharma won Health Canada approval for Procysbi, a cystinosis treatment that contains the same active ingredient as the old pill but has a coating that allows patients to take it every 12 hours instead of every six, a boon for parents and patients exhausted from middle-of-the-night dosing.
According to the CADTH's economic analysis, the old drug costs, on average, $5,450.99 a year for an adult patient. Procysbi would cost $321,711 a year for an adult. (The Patented Medicine Prices Review Board is currently investigating Procysbi's price.)
Now that a version of the drug has Health Canada approval, the older, cheaper version is not supposed to be available through the special-access program, although 63 Canadian patients - including Olivia - were still receiving it at their doctors' request as of last month, Health Canada said by e-mail.
As Horizon prepared to launch Procysbi in Canada, company officials reached out to Ms. Little and her husband, Chad, 36, who together run a small charity that raises money for cystinosis research. The company flew the couple to New Orleans in November, 2017, for what they thought was an information meeting about the new drug.
When the Littles arrived, they discovered that Horizon had hired a public-relations firm to teach them and a handful of other Canadians how to be better patient advocates. "They were talking about us having a problem with our voice," Ms. Little recalled.
"My question to myself was, 'Who's having a problem with the voice of our community? Us? Or you, because you have a product to sell?' " A Horizon official later sent an e-mail offering to sponsor a golf tournament hosted by the family's charity, an overture Ms. Little declined.
"That's just part of our DNA at Horizon," explained Matt Flesch, the company's executive director for product communications.
"We reach out to advocacy organizations and look for opportunities to support them - whether it be sponsoring a local event or helping with their education efforts."
Mr. Flesch said in an interview that Procysbi is a breakthrough for patients who struggled with the six-hour dosing schedule. The price, he said, is a reflection of the investment Horizon made in bringing the drug to market, including securing Health Canada approval.
Procysbi is now covered at a confidentially discounted price in every province where cystinosis patients live, Mr. Flesch stressed, which means no Canadian patients are paying for the drug out of pocket.
Ms. Little bristles at that argument. "Their whole thing is, 'Well, [patients] don't pay for it,' " she said. But, as a taxpayer, "I do pay it. We should all collectively care."
For some patient groups, speaking about the collective toll that exorbitant drug prices take on public drug budgets is a tricky business.
Durhane Wong-Rieger, the president of the Canadian Organization for Rare Disorders (CORD), which receives about 75 per cent of its funding from pharmaceutical companies, said she has come to realize that patient groups must talk about prices. "It's huge," she acknowledged.
But that does not mean patient advocates have a responsibility to publicly pressure drug companies to lower their prices. "I don't ask the governments to pay more.
Why should I ask the companies to pay less?" Ms. Wong-Rieger said. "Why is it my job to fight for what the right price is? I have no idea what the right price is."
As Ms. Elias of Myeloma Canada pointed out in her letter seeking public funding on behalf of the cancer-group coalition, there is a "natural alignment" between the patient groups fighting for access to new treatments and the companies that make them.
Ms. Elias herself is an example of that alignment: She joined Myeloma Canada in early 2016 after more than 13 years at Janssen, including as the drug company's national director of patient-engagement strategy.
She said she is a stickler for ensuring that neither Janssen nor any of the other pharmaceutical companies whose contributions make up about half of the group's budget have any say in Myeloma Canada's work - including submissions to the CADTH or news releases about drug coverage.
In a 2017 news release titled "Canadians Living with Multiple Myeloma Need Access to Therapies Now," the patient group called for public coverage of three new drugs, two of which had at the time received a do-not-list recommendation from the CADTH's pan-Canadian Oncology Drug Review (pCODR).
"We were not agreeing or disagreeing with pCODR, we're just saying, 'Health Canada said yes to these drugs,' " Ms. Elias explained in an interview. "It is a problem for patients because they're not getting access to these drugs."
One of the drugs mentioned in the news release, daratumumab, sold as Darzalex, is a Janssen product that costs more than $28,000 a month in the first two months of treatment, making it "one of the most expensive drugs per cycle that pCODR has ever reviewed."
The pan-Canadian Oncology Drug Review later reconsidered Darzalex when given in combination with two other drugs and recommended it be covered by government drug plans.
Like Ms. Elias, Teresa Pavlin, a spokeswoman for Janssen, said the company had no role in the news release.
For Sharon Batt, a Dalhousie University bioethicist and the author of a book about how pharmaceutical company money changed the breast-cancer movement, the problem remains that the money amplifies the voices of certain patient groups, not others.
"You have to be willing to listen to people who have a terrible side effect as well as the ones saying, 'This drug is great for me.' " The CADTH, she warned, "is just hearing one side of the story."
Ms. Little was not plugged in enough to know that her small foundation could make a submission to the CADTH for Procysbi.
The only patient group that contributed to that review was CORD, which disclosed that it received between $10,001 and $50,000 from Horizon over the two years leading up to the review.
However, Ms. Wong-Rieger said Horizon had no role in the submission, which reflected the results of a survey of patients and parents, many of whom were badly sleep-deprived.
"The majority of patients were very, very eager to get access to Procysbi," she said.
With files from Tom Cardoso HOW WE GOT OUR NUMBERS In order to figure out how often Canadian patient-advocacy groups declare a financial conflict of interest with pharmaceutical companies that have a drug before the Canadian Agency for Drugs and Technologies in Health, The Globe and Mail first searched for all of the patientinput submissions posted in full to the CADTH's website. In some cases, patient groups refused to grant the CADTH permission to post their written input; those submissions were excluded from the analysis. The Globe then read the conflict-of-interest declarations for every submission, entered them into a database and counted up the declared conflicts. The Globe cast a wide net, reviewing every patient submission it could find on the CADTH's website, including repeat submissions from the same patient groups on the same drugs. Sometimes, the CADTH reviews the same drug multiple times years apart - often because the drug maker is seeking the CADTH's endorsement to have a drug publicly funded for use in a new disease or in combination with other drugs. It should be noted that the advocacy groups that appear most often in the database represent patients for whom many new prescription drugs have arrived on the market - and before the CADTH - in the past decade. These groups are hardly alone in accepting pharmaceutical-industry funding.
Olivia Little, 9, right, prepares to take her daily medication at home in Port Elgin, Ont., on Nov. 21. Olivia is taking Cystagon to treat her cystinosis, which is a disease that causes cystine, an amino acid, to accumulate in various organs in the body. Without specific treatment, cystinosis can lead to end-stage kidney failure at around the age of 9.
Olivia holds a handful of the medications she needs to treat her cystinosis. The old drug, Cystagon, averages out to $5,450.99 a year for an adult patient. A newer drug, Procysbi, would cost $321,711 a year for an adult, although the Patented Medicine Prices Review Board is investigating that price.
An Irish-based company, Horizon Pharma, that makes the more expensive Procysbi, hired a PR firm and tried to enlist the Littles and other families to do patient advocacy differently. 'My question to myself was, "Who's having a problem with the voice of our community? Us? Or you, because you have a product to sell?' " recalls Olivia's mother, Erin Little, left.