Thursday, September 19, 2019


Before drugs can be prescribed on the NHS, they must be approved by the European Medicines Agency (EMA).
The EMA bases its decisions on clinical trial data submitted by pharmaceutical manufacturers. 

Cancer drugs have comprised the single largest category of new drug approvals in Europe. In 2017, more than a quarter (24/92) of EMA approvals were for cancer drugs. Between 2014 and 2016, the EMA approved 32 new cancer drugs on the basis of 54 pivotal studies. Of these, 41 were randomised controlled trials (RTCs) - considered the gold-standard for research because the new drug is compared against a placebo, and participants do not know whether they are on the medication or the placebo. 

Researchers warned thattreatment effects may have been exaggerated and called for stricter rules on how new drugs were judged, including a renewed focus on patients' overall survival instead of measures such as progression-free survival or disease response which "do not consistently translate to survival gains or quality of life benefits". researchers argue that uncertainty and exaggeration of the evidence that supports approval of cancer drugs “causes direct harm if patients risk severe or fatal adverse effects without likely benefit, or forgo more effective and safer treatments.” Inaccurate evidence also leads to intangible harms, which encourage false hope and create a distraction from needed palliative care, they add. 

The researchers found that 19 of the 41 RCTs (49%) were at high risk of bias "based on their design, conduct or analysis". Problems included such things as participants not being properly randomised, or a lack of "blinding" - a technique which means neither the participants nor the researchers themselves know who is on the drug or the placebo. Double-blind trials were less prone to bias, but more expensive to organise. 

Clinical trials have increasingly looked to alternative ways of measuring a drug's effectiveness in cancer patients, such as progression-free survival - the length of time without relapse.
These types of studies are cheaper and easier to organise because they can use smaller sample sizes and results are generally reported earlier - clinical trials are on average 11 months shorter than those using overall survival as the outcome. 

However, the BMJ study found that bias was more common where these alternative measures were used, and lowest in those which assessed drugs on overall survival.
NHS Scotland spent £1.7 billion on drugs in 2016/17, an increase of nearly 20 per cent in five years. 

Cancer drugs are driving most of the increase in pharmaceutical spending across the NHS, but the researchers noted that there is "no association between magnitude of benefit and drug price". 

In the case of leukaemia drug, pegaspargase (Oncaspar), all five studies examined were considered high risk, while breast cancer drug palbociclib (Ibrance) was approved on the basis of two studies whose results are considered potentially unreliable. The studies behind skin cancer drug trametnib (Mekinst) and immunotherapy treatment nivolumab (Opdivo) were also criticised by the researchers.

No comments: