The growing global health inequality of new drugs and clinical trials
At the European Cardiology Congress in Paris this week, the news is that cardiovascular medicine is still producing tonnes of new research and there are therapeutic advances in all areas from atrial fibrillation and stroke to heart failure and heart attacks. For example, there are 3 new oral anticoagulants (blood-thinning drugs) which offer true alternatives to warfarin for the first time in 50 years. All these drugs have shown superiority in recent trials presented at this meeting- rivaroxaban in ROCKET-AF, apixaban in ARISTOTLE and dabigatran in the RE-LY trial.
Salim Yusuf, arguably one of the most prolific clinical triallists and lead investigator in two of those trials, also presented the results of a different type of study, published in the Lancet this week. The PURE study included over 150000 patients with known coronary heart disease from 17 countries and showed that even in high-income countries. The drug treatments that such patients should be taking are well-established and available very cheaply-aspirin, beta-blockers, ACE-inhibitors and statins. Depressingly, the proportion of patients globally taking these drugs is less than 50% even in rich countries. In Africa, 80% of eligible patients were taking no drugs at all. As Salim Yusuf said, treatment gaps like this in the HIV/AIDS epidemic led to human rights arguments for broadening of antiretroviral treatment and mobilisation of the global health community and governments.
The inequality was also visible at concurrent “Meet the Triallists” sessions. Delegates clamoured to get to the trial update for the ARISTOTLE trial of the novel anticoagulant, apixaban, but I was one of only 20-30 people who heard Salim Yusuf talk about the PURE trial. Global health cardiology is just not sexy enough yet, even in the wake of the UN high-level meeting in September.
You could argue what is the point of all these fancy new drugs if we are failing to get simple, cheap, proven therapies to the people who need them most, even in rich countries. The tsunami of cardiovascular disease hitting all countries is not going to be touched by all the new drugs currently being trialled. We have to get better at translation. More research funders and senior researchers need to lead new trials with global health impact if we are to have any chance of focusing on problems worth researching.
Drugs in children: more is needed than just a spoonful of sugar
A recent study in BMJ Open used the newly developed WHO International Clinical Trials Registry Platform (ICTRP) to find out how many current studies recruiting children for drug studies collect pharmacokinetic data.
The findings of the study were shocking: only one-quarter of 1,081 trials studying medicines in children collect pharmacokinetic information. Further, only one-third of the medicines identified as a priority by the European Medicines Agency actually collected data (at the time of the study in 2008).
Well what is pharmacokinetic data and why is it important? Pharmacokinetics refers to the study of external substances after they are ingested in the human body. For example, when you swallow a pill, pharmacokinetics explains how long it takes your body to absorb the medication, how long it takes your body to break it down and how long the drug works for.
When children are given medication, doctors, nurses, pharmacists and patients assume that drugs would not be available for children unless they have been rigorously tested and understood. In fact, the truth is quite different. Off-label (outside the product license) and unlicensed (without a license for use in children) prescription rates in children range from 11-80%. There are significant gaps and inadequacies in research conducted in children.
Children are not just small adults and have different safety and efficacy profiles of medications than adults due to differences in physiology, disease pathophysiology, pharmacokinetics and pharmacodynamics. Even adverse drug reactions occur more frequently in children with off-label prescribed drugs.
This vital problem needs to be addressed at multiple levels and the WHO has taken a lead role. The ICTRP will help to improve awareness and make it easier to access accurate, up-to-date, understandable information about clinical trials in children.
The WHO has also launched the ‘Make medicines child size’ campaign in 2007. Hopefully this will address the lack of child studies worldwide as only 38% of trials in children are conducted outside of North America. Clearly studies conducted on children in the US or UK cannot be directly applied to children in Sub-Saharan Africa or India.
Outside of the WHO, the StaR Child Health initiative was founded to improve the design, conduct, and reporting of paediatric research.
A spoonful of sugar to help the medicine go down is not enough. More is needed to understand drugs in children.