Denial of access to a drug instead of a placebo

In Canada, the Special Access Program allows a doctor to apply to Health Canada to authorize a company to dispense a drug that’s in development. But no one can make the company do it. The Special Access Program  (SAP) allows practitioners to request access to drugs that are unavailable for sale in Canada. This access is limited to patients with serious or life-threatening conditions on a compassionate or emergency basis when conventional therapies have failed, are unsuitable, or are unavailable.

The push for access to trial-phase drugs has its beginnings in the 1980s during the early days of the AIDS epidemic. People were dying, desperate to get into clinical trials that might offer them a new lease on life and not satisfied that only half those participating would actually get treatment.

 The purpose of participating in a trial is not to access to a cure. The purpose of participating in a trial is to contribute to knowledge of the effects of the drug being tested. Clinical trials are done in phases. The first and second phases determine a treatment’s safety and effectiveness. Phase 3 involves a large group to confirm earlier results and compare it to other treatments. That usually means part of the group receives the new treatment and part does not.

It’s not known, at trial phase, whether a new treatment will work better than the current best practice. If it was, it wouldn’t be a trial — it would be treatment.

The very treatment you have today is because others participated in a trial.  Along the way, some people will benefit, some people will be harmed. But it’s a bigger picture, a different goal, that’s looking at a population of people and saying to the individual: “Can you help us achieve this goal for other people like yourself?”

But that doesn’t make it hurt less for those who feel the means to saving their lives or the lives of others they love is just out of reach because they weren’t picked for the testing of the drug which many hope is the miracle drug that will cure them.

Frank Burroughs founded the Abigail Alliance for Better Access to Developmental Drugs in Virginia after his 21-year-old daughter died of cancer. The family had lobbied hard for access to what’s now marketed as Erbitux, then a promising drug in trials but had been refused to be part of the testing of the drug.

Professor Arthur Schafer, director of the University of Manitoba’s Centre for Professional and Applied Ethics, says patients should have the choice to access experimental drugs. But he cautioned that usually, drugs aren’t the miracle drugs that people hope for. The drug may only add a few weeks or months, and side effects can possibly render that time the drug is taken as being wretched.

Many patients and their families think, and many people in society think that if you’re dying and your prognosis is very bleak, then you have nothing to lose. If you’re taking aggressive therapy, your last days, weeks or months of life may still not be spent quietly and in a dignified way by talking to your family, saying goodbye, putting your affairs in order if the side effects are wretched.

Adrienne Lotton is 34 years old, a newly minted veterinarian who organized food drives and went to the gym. Now, she’s stricken with a deadly illness. And she’s running out of time.

Her hopes of avoiding death or buying more time are caught in the web of medicine and moral quandary that surrounds access to developmental drugs. She is undergoing a wrestling match between the interests of one patient and many; between scientific rigour and desperate hope; between benefit and risk; ultimately, between the chance to live and certain death.

She was diagnosed with Stage 4 melanoma in the spring of 2012, not long after she had moved to Regina, Saskatchewan, to work at an animal clinic. Melanoma accounts for 5 per cent of skin cancers but 77 per cent of deaths. The five-year survival for metastatic melanoma is 15 per cent.

Lotton came home for treatment at Princess Margaret Hospital in Toronto. After radiation, chemotherapy and a new drug, Ipilimumab, she went back to work in Regina, back to the gym, back to her life. Three months later, Lotton’s checkup at Princess Margaret showed lesions in her abdomen. She came back to Toronto for good.

But there is a new drug called Inivolumab that is showing promising results in treating advanced melanoma in clinical trials.

Lotton made it into a Phase 3 trial last fall. But she landed in the control group that would receive currently proven treatments that, for her, aren’t working. She wasn’t to get the Inivolumab drug.

Lotton withdrew from the trial and her oncologist (specialist in cancer treatment) asked the pharmaceutical company, Bristol-Myers Squibb, to release Inivolumab to her on compassionate grounds. The company refused. Bristol-Myers Squibb hasn’t released Inivolumab outside of clinical trials. I can see why they made this decision. If they released the drug to her, then others outside the test and even those who are getting the placebos in the test would ask for the drug also. The company says there isn’t enough information yet to use it outside a trial. They would have to also do a separate test with her.

Darcy Doherty, a 48-year-old father of three, died of melanoma in July 2012 after waging a highly public campaign for access to it.

 Bristol-Myers Squibb sais, “We empathize with patients who have limited treatment options and will continue to assess available data on Inivolumab to determine if the established benefit/risk profile allows for expanded access use outside a well-controlled clinical trial in the future.”

For those, like Lotton, whose lives potentially hinge on a random selection of who gets what, it’s excruciating.

Dr. Janet Dancey, who leads the High Impact Clinical Trials program at the Ontario Institute for Cancer Research, says it’s a balance, between the care of an individual and research that improves treatment for all patients. She said,  “The desire to do the best you can for a patient and for a patient to get the treatment that you think could help them, versus the need to be certain that treatments really work and that there’s a real benefit and it’s worth whatever risk, that’s always going to be a tension. There are no easy answers to this. There’s no one-size-fits-all.”

Researchers are obligated to prove a drug or treatment is safe and effective,. And Phase 3 trials are the most rigorous testing that can be done. Treatments that showed great promise in early phases of testing have tanked in Phase 3.

Dancey said, “We’re all aware of those examples, where we thought from early results that we had a winner and in fact, what we ended up with was something that was no better and in a few cases at least, was actually worse.”

Lotton is meanwhile living with her mother at her mother’s home in Cobourg. She’s trying to get into another trial. She’s been upbeat through her illness, keeping a blog that documents her battle wryly, wittily, encouraging friends to donate blood to replace what she’s using through transfusions.

They are still hopeful, that the next trial will go well; that something will come out. They also hope that BMS will give them the drug that could save her.

It is indeed unfortunate that people who were receiving the placebo in the drug testing died before it was discovered that the drug being tested would have saved them. But if the people who are being tested for a new drug that may have the potential to cure them, decide to leave the test because they think that they may be receiving the placebo and subsequently seek the actual drug from the manufacturer then the purpose of the test is pointless.                           

Adrienne Lotton chose to leave the test in hopes that she could bypass the test by asking that the drug manufacturer give her the actual drug being tested. That is counterproductive to drug testing. I am sympathetic to her dilemma but if the drug is deemed to be successful as a cure, it will not be because of the efforts of this unfortunate woman who deserted the test in order to get the actual drug instead of what she perceived might have been a placebo.