Her husband’s diagnosis with melanoma led biomedical scientist Bettina Ryll to change how she thinks about drug development and risk

Bettina Ryll thought she understood clinical trials. She was taught about evidence-based medicine during her medical degree; she learned about medical ethics and research study design during her PhD in molecular biology.

“I thought I understood the process and believed that randomised placebo-controlled trials were the apex of sophisticated medical research.”

Then everything changed. Bettina’s husband was diagnosed with advanced melanoma in 2011, a disease for which the prognosis is very poor.

The standard of care for stage IV melanoma was chemotherapy which, says Bettina, essentially “never worked”. “Traditionally, late-stage melanoma patients have six-to-nine months,” she says.

Bettina and her husband had a friend working in the pharmaceutical industry who pointed them towards a clinical trial. The trouble was that the trial compared a promising new medicine with the existing therapy. Luckily, Bettina’s husband was randomly assigned to new therapy but the wait for the result of the randomisation was one of the worst experiences of her life.

“This helped me to understand the shortcomings of the current approach to drug development first hand,” she says. “We cannot go on like this.”

She met a group of people online – patients and their loved ones – looking for information about trials and treatment options. “When you look at how trials are designed, some have inferior comparitors and will be of no use to the patients who are taking part. We started discussing what kinds of trials we would want to go on; that would be fair on us.”

Then, less than a year after his diagnosis, Bettina’s husband died.

“I got sucked into advocacy – somewhat reluctantly. When we went back to look at the alternative drug development pathway we had described in our discussions, it looked very like adaptive licensing. We realised that there really was a better, fairer way.”

Bettina founded the Melanoma Patient Network Europe (MPNE). The deeper she got into talking with patients and their families the clearer was the mistmatch between the drug development timeline and the timelines facing patients.

“We had a conference on clinical trial design and everybody spoke of the same problems with access and systematic learning. We effectively have no access to the most promising drugs. It doesn’t help if people get excited at ASCO but it takes years before the medicine is available,” says Bettina.

For patients with stage IV melanoma, waiting five or ten years is simply not an option. “Today’s patients will be dead by then. In fact, if things do not improve, 12 generations of patients will be dead a decade from now.”

MPNE is pushing for patient input in clinical trial design at a much earlier stage but also wants to see this combined with a payer perspective. After all, if the drugs are not reimbursed, early approval is of little value to patients.

Rethinking risk

“The speed of development has to be proportionate to the rate of death,” says Bettina. Patients with life-threatening diseases have a very different view of risk to those who decide what levels of risk is acceptable in a trial or in drug approval, she says.

“At the moment the message appears to be ‘Let our patients die in safety’. Today’s patients want a drug now – not to know that a new melanoma patient might get a drug a few years from now when todays’ patient is dead.”

So how can the patient perspective inform trial design? At their conference later this month (April 24-26), MPNE will bring together around 30 stage IV melanoma patients and their carers from 18 countries to discuss how they view risk.

The group will run through a range of hypothetical scenarios to explore the trade-offs people with advanced cancers would make in return for potentially life-extending treatment.

The MPNE is also taking part in the Get Real project funded by the Innovative Medicines Initiative. They have been working on a survey to help deepen understanding of what melanoma patients consider a good trial.

The task ahead is large and complex but the group could hardly be more motivated.

“We are fighting for the lives of people we love. Every delay in progress kills people.”