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Evidence vs access – addressing the balance in assessing new cancer drugs


A study in the BMJ last week has opened up a debate over the level of evidence needed before a drug is made available to patients. Here, our Science Information and Policy Officer, Dr Sam Dick, takes a look at the study in more detail.

Posted on 11 October, 2017 by Dr Sam Dick

Green coloured pills

It was a headline-grabbing conclusion. Only half of the cancer drugs authorised by the European Medicines Agency (EMA) showed a significant improvement in overall survival or quality of life when they were approved or in follow-up studies, according to a study published in the British Medical Journal last week.

The research has prompted a lot of discussion about how new drugs should be assessed, what constitutes sufficient evidence for approval, and how we balance a robust decision-making process with the need for speedy access to the latest treatments.  

It’s a topic of great interest to us here at The Institute of Cancer Research in London – given our critical role in the discovery and development of many new cancer treatments.

I decided to take a closer look at the study and its possible implications.

Treatment effectiveness measures

The authors of the study looked at 48 drugs approved for 68 uses by the EMA from 2009-2013, and assessed whether they improved survival or quality of life for patients.

There are a number of ways you can measure the effectiveness of a new treatment in a trial – from long-term measures such as how long people on the treatment survive (overall survival), to shorter-term measures, like the length of time before somebody’s cancer begins to get worse (progression-free survival).

These outcomes are called endpoints, and the primary endpoint of a study is the one the researchers decide at the outset of the study should be used to decide if a new treatment is more effective when compared with another treatment or a placebo.

Another possible endpoint for a study is the patient’s quality of life, where a patient’s overall wellbeing and ability to continue living a normal life are assessed during treatment.

Surrogate endpoints

The study found that at the time of approval, while all the drugs will have shown evidence that they were effective in some way, only just over a third of the approved drug uses showed evidence of increasing survival. And only 1 in 10 had evidence that they improved quality of life.

A further eight drugs were found to increase survival or improve quality of life in studies performed after approval.

Overall survival was used in only a quarter of trials as the primary endpoint, with the others approved on so-called ‘surrogate’ end points including progression-free survival and various laboratory measures of a patient's response to the treatment.

None of the approvals had used quality of life as a primary endpoint, and only just over half of the trials had measured it at all. The writers of the study suggest that using surrogate endpoints as the basis of approval, rather than overall survival, leads to ineffective drugs making it to market.

However, surrogate endpoints such as progression-free survival can also be valuable outcomes in their own right. Many drugs may offer limited increases in overall survival, but can improve the quality of life of patients significantly in the time they have left by temporarily stalling the progression of the disease.

And overall survival data tends to be collected in large, phase III clinical trials, which are very expensive to run, and take a long time. The ICR and many other organisations have been arguing that we need to be flexible in the way drugs are assessed, in order to speed up the approval process and get the best new treatments to patients more quickly.

Drug assessment flexibility 

We have increasing scope to be more flexible in the way drugs are assessed without sacrificing quality of evidence. It’s now possible to assess many of the new generation of targeted therapies in smaller, smarter trials, that evaluate the treatments in subsets of patients who have been selected because they are most likely to benefit.

It is of course vital that new drugs are shown to be effective, but with high-quality, innovative clinical trial design, it is possible to provide good evidence of effectiveness from smaller, earlier studies.

As part of the mix, we believe it is important that licensing bodies can assess evidence other than overall survival where appropriate, as one way of speeding the progress of new drugs to patients.

Download and read our factsheets where the ICR has outlined its position on a number of policy issues in scientific and medical research.

Read more

Access to the latest innovative treatments

I spoke to Professor Winette van der Graaf, Professor of Personalised Oncology here at the ICR, to find her views on the study. She told me:

“In recent years regulators such as the European Medicines Agency have started to show more flexibility in their approval of cancer drugs – and we absolutely applaud them for this.

“If we want to speed up access for patients to the latest, most innovative new treatments, it’s essential that regulatory bodies and indeed NICE are willing to look at data other than just overall survival from large phase III randomised trials.

“It takes a long time and costs a lot of money to take treatments through phase III trials and demonstrate an overall survival benefit. Showing more flexibility, such as by evaluating data from smaller, smarter trials where drugs are targeted at those patients who are most likely to benefit, is essential if we are to get new drugs to patients quickly and at a cost that is affordable for the NHS.

She added: “In my area of research of rare cancers, the level of evidence called for in the BMJ study is very hard to obtain, meaning that these patients would find it extremely difficult to gain access to new treatments.

“But the authors are right in saying that there is room for improvement in the design of clinical studies. Ideally, studies should also try measuring early markers of treatment failure, so that health authorities can make well-balanced decisions.

“We also need to look at different types of clinical studies, including evaluation of the impact on health related quality of life, and to continue to collect data after approval in a clinical setting.”

Focus on health related quality of life

The ICR believes that too much emphasis on the need for phase III, overall survival data could slow down the passage of the latest cancer drugs to patients.

However, the new study does make some good points about the design of clinical trials, and particularly about the importance of emphasising quality of life.

Importantly, in these studies we should focus on health related quality of life - the factors directly affected by a patient’s treatment - and not on the generic broad term of quality of life, which can include a number of other factors.

We believe that health related quality of life is something that needs to be more extensively and consistently documented for new drugs. This is particularly important post approval when it’s possible to assess health related quality of life in the day-to-day lives of patients.

The ability to live as normal a life as possible is an important outcome for people living with cancer. Cancer can have a lot of symptoms affecting people’s lives, and alleviating those at least partly could have a meaningful impact. 

I hope that regulatory authorities such as the EMA continue to recognise the importance of rapid access for patients, and that future regulations are smarter rather than simply being more stringent.


policy Winette van der Graaf
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