Since 2015, the pharmaceutical company Hoffman-LaRoche has been gearing up for a trial looking at whether a drug they’re developing for patients with high risk of recurrence following surgery for kidney cancer is better than the current recommended treatment – to wait and watch, with scans every three months.
The trial would divide participants into two groups: one group would get the intravenous drug therapy, the other would get saline solution. It’s the kind of double-blind randomized control trial that’s considered the gold standard for amassing strong, reliable data.
But it’s also the kind of trial that leaves some patients incredulous.
“Would anybody recommend that trial to their mother or father? Would they drive them two hours into a cancer centre to have saline infused? It’s an industry-sponsored trial with everybody ticking boxes but no one thinking about this from a patient perspective,” says Deb Maskens, co-founder of Kidney Cancer Canada and vice chair of the International Kidney Cancer Coalition, who also volunteers as a patient expert for researchers needing input on trial concepts and design.
That type of trial may have been designed to make the data “crisp and clear” for regulators (who often demand placebo-controlled trials), Maskens says, but likely won’t have an easy time recruiting patients. That means delays in discovering whether the drug works, and further delays for patients in accessing a potential new treatment.
“Patient engagement” is a frequently used word in healthcare circles, with hospitals, clinics, advocacy groups and even regulators seeking ways to consult directly with patients and caregivers and to reflect their views in decision-making processes.
Pharmaceutical companies have been slower to adopt patient engagement strategies, largely because legal and compliance teams often caution researchers to maintain a distance between themselves and patients. But they too are now beginning to look for ways to better incorporate patient feedback, both on drugs on the market and drugs in development.
AstraZeneca, Pfizer, GSK (GlaxoSmithKline) and Amgen all have advisory boards that involve patient representatives. And some patients are eager to collaborate on clinical trial design, to influence the design of trials like the one described above.
Yet it’s an uneasy relationship, with pharmaceutical companies wary of falling afoul of advertising and marketing regulations, patient groups worried about perceived corporate influences and patients uncertain that their health priorities will trump profit potential.
Patient involvement early in trial design
Right now, any interaction between drug companies and patients typically comes after a drug has been developed and released, when drug makers look to patients to provide “patient reported outcomes” to determine whether a drug is having its intended effects and meeting patients’ expectations.
“Not just did the patient live two to four months longer but what was patient’s life like?” Maskens says. “How was their life impacted, what was their quality of life, did the drug meet the goals that they had?”
“Ultimately, these drugs are being developed for the patient. I think it’s really well-known now that drugs serve no value to the health system or the patient if the patient will not take them,” says Shurjeel Choudhri, senior vice president and head, medical and scientific affairs at Bayer Inc.
While input from patients is valuable in the later stage of a drug’s release, the ideal would be to involve patients earlier in the design of Phase II and III studies, Choudhri says. He acknowledges Bayer is at “very preliminary” stages of patient engagement as they determine how to interact with patients within the boundaries of compliance.
“In the ideal world, you want to have patient input at all levels. How do you do it in an ethical way, how do you do it where patients may not have the [medical or technical] background?” he says.
“This is a global struggle. Everyone is having this conversation,” says Dawn Richards, the associate director of patient and public engagement at Clinical Trials Ontario. She says “it’s scary” for drug makers who don’t want to be seen violating processes that demonstrate compliance with the rules and regulations of drug development, sales and marketing.
She says some drug makers are still trying to figure out just how much to invest in patient engagement.
“For pharma, a lot of return on investment is measured in dollars and this one is going to be a tricky one because there are so many factors involved in it,” Richards says. “We’re convinced this is the right thing to do. We have to move beyond physician-as-proxy for the patient voice. We know that by doing this, there will be better products and better services. Revenue follows that and profit follows that.”
Be Ready, Be Bold
Currently, very few patient groups or pharma companies have codes of practice to address how the two groups could work more closely together. EUPATI, the European Patients’ Academy, released guidance for patient involvement in industry-led research and development just last year. They emphasize transparency and clearly defined and agreed upon objectives and timelines.
The Huntington Society of Canada realized early on that if there was to be hope of a cure for Huntington’s – or medications to control slow, stop or reverse symptoms – patients would need to be more involved in setting and designing the research agenda.
Bev Heim-Myers, the group’s CEO, says people living with Huntington disease — a fatal genetic disorder whose symptoms can include a progressive loss of mobility, mood and personality changes, involuntary movements known as chorea and a slurring of the speech — would prefer to see drug development dollars go to treatments that would slow or reverse symptoms related to cognitive function. But pharmaceutical companies have been pursuing research into medications to control tremors and chorea.
“I think pharma has always felt that they know what’s right and they know what they’re looking for and they need this many subjects to prove it and to move it forward,” Heim-Myers says. “The economic drive in pharma is not always a benefit to their thought process.”
Over the past five years, the Huntington Society has worked with patients, funders, researchers and other experts to develop their “Be Bold, Be Brave, Be Ready” strategy for building research capacity and funding, as well as guiding patients and others through the research process.
Heim-Myers acknowledges pharma was not invited to be at the table – there’s just not enough trust yet.
That’s why many predict it will take a cultural shift to bring about meaningful patient engagement in drug development.
“Every pharmaceutical company says that they are patient-centric and that the patient is at the heart of everything that they do,” Maskens says. “My challenge to them would be to prove it. For any clinical trial that they put out, for any piece of research, show me where the patient involvement was. Not just in the end but right from the very conception of the research, looking at what needs to be done at the research prioritization level.”
Building trust
Pharmaceutical companies know they need to build that trust, Choudhri says, starting with providing better information to patients and clinicians.
“There’s a lot cynicism out there and we want to do it the right way so that we’re being fair to the patients and it’s not being seen as something where we’re trying to influence the patient rather than get patient input,” he says.
Some of that cynicism is bred by media reports showing patients can become powerful lobbyists pressing for provincial formularies to cover the cost of pricey new drugs.
“I think pharma has a genuine desire to reach real patients, they just haven’t fully figured out how to integrate that into everything that they do,” Maskens says. “Right now, they struggle with how to operationalize ‘patient-centricity’ and what that really means. It means they’re going to have to do business differently.”
Richards, who also consults with international drug makers to help them build patient engagement strategies and connect with patients, says pharmaceutical companies need to prove they’re not only listening to patients, they’re taking their advice and turning it into action.
Patients will also want to know when their expectations can’t be met and why. “They’ll need to tell people they’ve consulted about how their input and voice is influencing actions internally,” Richards says. “This is where the struggle lies again.”
But there are certainly benefits for both sides: for pharmaceutical companies, working with patients to design trials could increase participation.
A Canadian Partnership Against Cancer report on Canadian participation in clinical trials “describes a real dismal scene,” says Barry Stein, CEO of the Colorectal Cancer Association of Canada.
In Canada, clinical trial participation rates range from less than one percent in the Maritime provinces to 6 percent in Alberta. (The UK, which has invested in improving clinical trial education for patients, managed to raise its participation rates to 13 percent, one of the highest participation rates in the world.)
In June, Stein’s group will host a consensus meeting bringing drug trial sponsors, researchers and patient groups to together to help develop a pathway to placing patient groups more fully into clinical trial design.
“At the end of the day, what we’re looking to do is to encourage more clinical trials, encourage participation of patient engagement in terms of design and protocols, increase of recruitment and retention in trials and follow up in terms of real world evidence,” Stein says.
Understanding patient concerns may also help drug makers develop medications that encourage adherence – such as medications that involve a single dose, versus those that are required to be taken three times daily.
“If the development has happened and studies have been done to look at what’s important to the patient, it allows you to better target the messages for the patient as to why it’s important to take the medication, what the medication will do for them,” Choudhri says.
Heim-Myers says the evolution toward patient-oriented research has been gradual. “It’s about a person, it’s not about a subject in a study. I think that over the last six years, the lights have gone on,” she says, noting that researchers used to decide their priorities and follow their hypothesis, rather than wonder if their findings would be relevant to the people with the disorder or disease they were studying.
“We are convinced that bringing people into this fold in a way that hasn’t been done before can only move the field forward in a positive way,” Richards says. “It has ripple effects throughout the clinical research system. Patients are able to bring this really pragmatic, really realistic perspective about what they’re willing to deal with in terms of potential risks and potential benefits within protocol design.”
This post has been updated to correct information about the Hoffman-Roche trial.
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In the late 1990s a group of telemarketers out of Quebec were calling patients in a free trial or Remicade, at least some for off-label use for Crone’s Disease, and told that their free trial must end soon. Remicade is given by needle twice a month at a cost of $ 2600. and was not covered by the provincial formularies. 11% of patients on Remicade will get cancer. The patients were sent form letters to rewrite and send to their provincial Minister of Health as if they were their own words pleading him or her to put Remicade on the formularies because the drug helped them and they were about to be cut off. Sleazy. This was discovered when the Ontario Minister of Health was chatting with his counterpart in Manitoba who was getting the exact same letters. Patient engagement is about using patients to sell more of the highly expensive drugs and is generally unethical. They don’t need patient help designing clinical trials. Decisions regarding which drugs to develop are made for purely economic reasons. Making patient groups think they have say in that is dishonest and cruel. They want their names and email addresses to build relationships like any other business. BTW when a patient gets harmed by a drug the drug companies never admit their drug caused harm, and always blame the patient and the doctor in court, real fair weather friends! If they have a direct relationship with a patient that defence won’t stand. Can’t blame the doctor. That’s why they are being cautious. Drugs are not cars, or real estate or life insurance. There should always be a learned intermediary between them and their end customers, and that intermediary should not be taking any cash, shares, lunches, baseball tickets, or free trips or free samples in exchange for his or her signature on a prescription pad, which is still common. Nor should they act as shills for Big Pharma to bird-dog patients to target for those “relationships”.
The question remains how does pharma understand what patient centricity really means when the business priority is to focus on what matters to shareholders not the real stakeholders. To start climbing out of this ethical dark hole pharma can take guidance from the increasing volume of evidence around patient experience coming from places like The Beryl Institute and the National Academy of Medicine. Understanding how to engage with patients is no longer just a “nice to have” but for leading healthcare institutions and businesses it’s now core business. This evidence reinforces a path to patient engagement through a commitment to these four pillars:
(1) Visionary and purposeful leadership. Leadership sets the tone for a top down shift in organizational culture. A dedicated role to patient engagement in the C-suite that’s funded and supported is an example of that commitment.
(2) A thoughtful definition of patient engagement that draws on the values that leadership has committed to. Employees can’t believe in something if there isn’t a clear organization wide definition that they all understand and share.
(3) Investment in workplace culture. Change isn’t easy for anyone. The investment in human capacity is a top priority. If staff is to make good decisions based on a solid definition rooted in a new value system, then they need to be supported throughout this transition to acquire the skills and tools they will need to be successful in the new environment. They will end up making better decisions with patients for the company.
(4) A Language of Partnership. The dialogue with patients needs to shift from the current transactional model to one that is interactional. This new method of conversation and engagement is an acquired skill. Both patients and staff need support to understand how to apply the principles of transparency and collaboration to create safe spaces for authentic interaction.
It’s not magic. It is hard work though, won’t happen overnight, and will be difficult for many organizations. Six years ago companies interested in real change would have found themselves alone in a wilderness. Since then empowered patient experts who are capable and qualified like Dawn Richards can help companies navigate to a more authentic and meaningful level of engagement with patients that will contribute to a sustainable and compassionate health system. With the evidence now strong and clear that successful outcomes are associated with an organization’s level of patient engagement activation, there is no longer any excuse to not make it core business.
Having one group receive treatment while a control group receives placebo doses is the correct way to do this research; however, denying the control group treatment is unethical. While this article points out that trust needs to be built between patients and Big Pharma, this trust is a long way off. Far too many times we have seen drug companies buy the rights to a drug just to raise the price, sometimes astronomically. When asked, ‘How could you in good conscience do that?’ the answer is always the same. ‘We are not in the business of helping people. We are in the business of maximizing shareholder profit.’ Patient engagement cannot be recommended until a complete paradigm shift occurs. This shift needs to be away from maximizing shareholder profit and towards patient care while making a fair profit. This paradigm shift will not occur in my lifetime.