Controversial cancer treatment on children at a top Canadian hospital – The Fifth Estate

Controversial cancer treatment on children at a top Canadian hospital – The Fifth Estate


[♪♪] -[Pasquale] The 7th
of November, 2016. A big day for Montreal’s
Sainte-Justine hospital. Ministers and dignitaries
celebrate the opening of a brand-new research centre. [Speaking French] -[Pasquale] The bright and
modern building is in the west wing of the
children’s hospital. But, in the east wing,
at the very same time, a crisis is unfolding. For five days, Health Canada’s
inspectors have been seizing files and searching computers
at the Charles Bruneau pavilion, reserved for
children fighting cancer. Health Canada has just received
an anonymous complaint about Dec Gen, A clinical drug trial for
children with terminal cancer. The reputation of one of
Canada’s top pediatric hospitals is in jeopardy. By the time the
inspectors arrive, the study is already in trouble. One child dropped out,
because of side effects. Four others died. And the last of the six children
will die while investigators are working. Within weeks Health Canada
would conclude that the study should be suspended. Was Health Canada
right to close the study? Oh, yes. Absolutely.
-[Pasquale] Why? Jonathan Finlay is the head
of the neuro-oncology department at the largest pediatric
hospital in the United States. There were too many violations
and they were absolutely appropriate in
shutting it down. It would have been
wrong if they hadn’t. -[Pasquale] It wasn’t so long
before that hopes were running high for the study. In 2015, it was billed as the
first of its kind in the world. For the first time,
Sainte-Justine’s oncology experts were to conceive and run
their own clinical study instead of one designed by a large
pharmaceutical company. [♪♪] The Dec Gen study’s goal was to
look at the effects of combining decitabine, an existing
chemotherapy drug, with genistein, a chemical
compound derived from soy, a combination that had never
been tested on children but could give a sliver of hope
to those with no other option, or so researchers said. Mai Pham and Toan Nguyen
are both pharmacists and parents of three children
Liam, Elaine, and Lena, diagnosed with brain
cancer, at the age of 9. [Speaking French] -[Pasquale] That’s when
Sainte-Justine told the family about the Dec Gen study. Lena would be the
first patient to sign on. Deep down, Lena’s parents
knew their daughter would not beat the cancer. Still, they agreed to
take part in the study. -[Pasquale] The miracle
did not materialize. Lena died of cancer 27 days
after her first treatment. -[Pasquale] That was
December 2nd, 2015. Lena’s parents didn’t hear
another word about the Dec Gen study. Shockingly, it was only
much later they learned the chemotherapy drug their daughter
was given had actually expired. The doctor in charge knew it
and still ordered the infusion of medicine to continue. We found proof in
the medical records. Dr Michel Duval runs the
hospital’s haemato-oncology department. He doesn’t see the problem. Lena didn’t suffer any
harmful side effects from the expired medication. Her parents were devastated
but as pharmacists they at least hoped the study would
amount to something. Now they’re not so sure. They’re absolutely right
because it calls into question the validity of any results,
whether they’d be negative results or positive results. -[Pasquale] As they dug deeper,
Health Canada was discovering a disorganized and
incomplete drug trial in a world where precision,
care, and respect of scientific norms are valued above all. You’ve got to follow every
single little step by the book and keep track of everything
because it’s very complicated and if you get anything
wrong it could put in jeopardy the entire study. You have detailed procedures,
you’re following a checklist like a pilot on a plane. And you don’t go wrong
because if you go wrong the plane crashes. -[Pasquale] The research
centre’s own staff was worried about a disaster coming. Eight months
before the inspection, they warned their bosses. [♪♪] -[Pasquale] It was a
high stakes experiment. The combination of decitabine
and genistein had never been tested on children. Although it was tried on mice
and adults without significant results according
to our sources. It was on that tenuous basis
that researchers submitted their protocol for the children’s
study to Health Canada. The protocol is like the
bible of a clinical study. How would you
characterize this protocol? Poorly written. Superficially written and
superficially documented in terms of the background. They could have done
a much better job. -[Pasquale] Doctor Finlay
deplores the lack of clear scientific reasoning
in the protocol. But he does believe the drug
combination was worth trying. Yeah, I thought the rationale
was quite sound for that. The idea of looking at
the two drugs together. It seemed like a cute idea. -[Pasquale] What is the
goal of an experimental cancer trial, what researchers
call a phase one study? You’re testing for toxicity. You’re trying to find out
can we use this medication on a patient population and
how much medication can they take before it
becomes too toxic? The goal is not to
provide therapy. -[Pasquale] Maybe it’s not
but we never really know what doctors say when they’re
trying to enroll patients. Do they know what
they’re getting into? Are they feeling the pressure? This is how the Dec Gen study
was sold to Jenifer’s family. Nervous, likely because Jenifer
knew what was to come. She’d already been through five
rounds of chemotherapy and a bone marrow transplant to treat
two different forms of leukemia. As they do with all important
medical consultations, the family recorded the
doctor’s presentation. It’s much easier
than taking notes. It’s Dr Yvon Samson, one
of the researchers who speaks to the family. He is supposed to present
the study objectively. Remember, the primary goal
is not to cure the patient. It is a phase one study
he says to the family. But he also says
another word, a word everybody remembers. It was the word “remission”. -[Pasquale] Remission?
-Yeah, remission. It was significant
that we heard that word. It was the next important
step in her treatment. Get to remission. Be able to do a transplant. -[Pasquale] Nine times. That’s how many occasions
the researcher says the word “remission” during the meeting. -[Pasquale] He mentions
up to 12 rounds of chemo even though the other
patients can only endure one or two. But Jenifer’s
family didn’t know that. All they could think about was
the possibility of remission. Her brother Michael. It actually meant everything
because if there wasn’t any chance of remission,
I would not have advised her to go that route. There were other treatments,
trials out there and we would have gone with
those other options. -[Pasquale] Bryn Williams Jones
looked over the full transcript of the discussion between the
doctor and Jenifer’s family. Why, he asks, would anyone keep
bringing up the possibility of remission in an
experimental trial? You don’t talk about that in
a phase 1 cancer study with children who are dying because
what you’re doing there is you’re holding out a possibility
that is unrealizable. That’s unfair. -[Pasquale] If you were
wondering how a truly informed consent interview should
look like according to professor Williams Jones,
this is it. We don’t know if it helps and
even if it helps we don’t know if it’s worth the side-effects
that you could potentially have. Nausea, tiredness,
fever, decreased… -[Pasquale] In this PBS cancer
documentary, a researcher lists in detail all of the
side-effects the child involved in the trial
could experience. As you can see,
the list is long. -[Pasquale] The parents’
hope slowly fades. It was an excellent example
of how to do recruitment. The family is crying. They’re sitting
there trying to decide should they participate? And the clinical team
who is recruiting is giving all the information
and they’re making it really clear that the chance of
it succeeding is minimal. This is probably the hardest
decision along the way that you guys have to make. -[Pasquale] When we come back
Jenifer makes her decision and the hospital fights back. [♪♪] [♪♪] -[Pasquale] May 2016. Montreal’s leading
children’s hospital, Sainte-Justine, is enrolling
young patients in a drug trial it’s hoping will make news. 20-year-old Jenifer and
her family have to make a gut-wrenching decision,
whether to take part in the study. That is why the
researcher, Dr. Samson, tells Jenifer to think
about it for a few days. She is relieved. But a few minutes later… You certainly don’t line up the
next step before the person has even consented. -[Pasquale] The operating room?
-Exactly. You just don’t do that. You don’t put people in a
pressured environment where they feel like they have
to decide quickly. That’s unethical. -[Pasquale] Dr Samson
did mention that a cure was improbable. We wanted to ask
him about the tape, but he refused to participate. Instead, the hospital offered
up four people to answer our questions. So, was it fair to raise
the possibility of remission with Jenifer? -[Pasquale] Jenifer
thought about it for three weeks and
finally, she said yes. On May 26th, 2016, she got
her first dose of decitabine. -[Pasquale] But
Jenifer was not okay. She would only receive
one dose of decitabine. She was quickly diagnosed
with a rare fungal infection, “possibly related” to the drug. In her state, Jenifer had a
serious chance of catching a deadly infection, 39% in fact
according to the study protocol. A number that no one in
the family was aware of. So, what did you feel
when she basically died in a little bit
more than a month? It was shock. We were in shock. It was very sudden. It was very sudden. We felt, like, uh, lost. -[Pasquale] Jenifer died
on June 23rd, 2016, from her cancer and respiratory
complications from the fungal infection. Jenifer left behind a legacy. She and her family had
spent years raising money to fight cancer. They believed in
cancer research. They still do. [Speaking French] [Laughter] -[Pasquale] Three months
after Jenifer’s death, five-year-old
Guillaume Daraóche, suffering from leukemia, is
about to become the sixth, and last patient. Like each and every parent,
Guillaume’s mother and father signed the written consent form. It’s supposed to list
clearly the trial’s risks and possible benefits. So far, it’s an incredibly
evasive language. -[Pasquale] Leading cancer
ethicist Jonathan Kimmelman evaluated the 15 page
document for us. He finds it unbelievable
the consent form refers to a possible decline
in the disease. Instead, it should have said… -“If you participate in the
study, the prospects of cure “or the prospects of extending
your survival are very, “very remote. “However, by contributing,
you may be helping to advance “our understanding
of your disease.” -[Pasquale] Nowhere is this
written in the consent form. Guillaume’s parents,
Sylvie and Richard, sign it on September 27th, 2016. -[Pasquale] But on the day
Guillaume was to start the trial, a big problem. Some of his enzyme
levels are too high, higher than the protocol allows. But not enough to
worry the doctor. So, Guillaume is
allowed to begin the trial. A mistake at the hands
of the research team, says our expert. It’s in there as an
on-study requirement, and you have to abide by that. If it says something in there,
we’re not allowed to deviate. -[Pasquale] And what
does that mean? The patient should not have
been allowed on the study. -[Pasquale] Ethicist
Jonathan Kimmelman sees another problem
with the research team. In documents we’ve obtained,
the researchers make claims about the patients’
chance of survival. I don’t know where
they got that number. I’ve never seen
numbers like that. I don’t even know how
you could quantify that because usually survival is not
even measured in a way that’s reliable in phase 1 studies so
that’s certainly not consistent with the numbers that I’ve seen. -[Pasquale] From what you
know, that is untrue? I have no basis for
thinking that’s true. -[Pasquale] Guillaume
died of leukemia and of a terrible infection,
as Jenifer did. The Dec Gen study was suspended
on the day of his death, five weeks after
he’d been admitted. And there was more bad
news for the hospital. In their report,
two months later, Health Canada came
down hard on Sainte-Justine. 76 violations of the
Food and Drugs Act, including 23 critical ones. Violations that presented a
danger to the trial’s subjects or undue risk to their rights,
their health, and their safety. To have Health Canada intervene
in a study and say there’s this shopping list of problems
is extremely damning. Even a couple of errors would
be an alarm bell for a research team but to have a
long list like that? That’s a huge problem in a team. -[Pasquale] The
list is very long. Serious adverse effects
and a death not reported to Health Canada,
incomplete research files, staff that wasn’t
adequately trained, and on at least three
occasions, expired medicine like Lena received. Violations that the
hospital describes as “administrative mistakes.” They don’t seem to
know what they are doing. These are not
administrative errors. These are problems with the
culture of the research team and that research group. -[Pasquale] The same team
that did not tell any of the parents about the
suspension of the study. [Speaking French] In fact, we were
the ones to tell them. [♪♪] -[Pasquale] And something
else was troubling. The hospital’s ethics committee
only learned of the study’s problems on the day
of the suspension. So, who was watching
over Dec Gen? Scientific oversight
would normally be done by an external firm. But hiring one was too
expensive for Sainte-Justine. Who, then, was
monitoring the data? A hospital employee. That’s unacceptable
according to Jonathan Finlay. You need external monitoring. So, the question should be asked
whether an institution that does not have the experience and
expertise conducting a phase 1 trial should be in the business
of doing phase 1 trials. -[Pasquale] The researchers
did not take the suspension very well. Sainte-Justine fought hard to
get Health Canada to reverse the decision. For more than a year the
debate went back and forth. Yeah, it seemed very strange. You know, if this was an
FDA-regulated site visit, they wouldn’t have taken
any of those back answers. They would have just,
“you’re closed down.” -[Pasquale] Health Canada
ultimately determined that the children died of their
cancer and that side effects were in accordance
with the protocol. But they should have
been reported because of their frequency. And in the end, Health Canada
stood by its decision to suspend the study. [♪♪] As for the scientists, they
still believe that the Dec Gen combination merits a
second clinical trial. [♪♪] [♪♪]