Clinical trials not immune from poor quality drugs
There is an increasing body of evidence to suggest that significant quantities of medicines and medical products, especially in low and middle-income countries, are of poor quality. Malaria researcher and drug quality expert Professor Paul Newton, of the Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit in Laos, explains the latest research findings and explores some of the recommendations to improve medicine provision for clinical trials…
Substandard medicines (due to errors in factory production) and falsified medicines (due to criminal fraud) are profoundly neglected global health problems. Poor quality drugs have the potential to deny patients and their families the full and expected benefits of modern medicine.
Global and national health policy decisions are often made using evidence generated from clinical trial reports. Until recently it was believed that trials were immune from the issue of medicine quality. However, recent research investigations suggest worrying evidence of poor quality medicines administered during patient trials.
Clinical trials are the trusted method of providing the results needed to make important policy decisions about whether medicines are safe, efficacious and provide value for money. Patients who volunteer to participate in trials do so with the knowledge that the results will be reported transparently, and without bias, so that ultimately many other patients can benefit from the scientific findings.
Policy guidelines have improved the practice of medical research, especially clinical trials, and helped to ensure that trials are more carefully planned, implemented and reviewed. However, some guidelines need to be strengthened further to include clear guidance on how to monitor and safeguard the quality of medicines used in patient trials.
Working with a team of international medical experts, we recently compiled a number of findings published today in the British Medical Journal. The results highlight the apparent inadequacies of existing clinical trial guidelines, and the absence of sufficient checks in place to safeguard the quality of medicines used during patient trials.
One report of antimalarial drugs that were planned to be used in pregnant women in Africa, describes that one of the brands contained less than 90% of what the label stated. Our study also describes problems with a trial of the efficacy of vitamin A in Tanzania, Africa. Thirteen months into the trial it was found that the amount of Vitamin A supplement had deteriorated to only 32% of the stated amount of vitamin A, despite appropriate storage conditions.
Perhaps surprisingly for some, our research team found that the issue is not just confined to the developing world. A cardiac drug shipment worth £1 million was sent from the UK to a pharmaceutical company in the USA in 2007, for use as a comparator in a clinical trial. Suspicions raised by the tablets’ weight led to the discovery that the entire consignment was falsified, containing only 50-80% of the drug stated in the consignment.
As a global health community we should call for urgent changes in the guidance for checking the quality of clinical trial medicines. Guidelines such as the Consolidated Standards of Reporting Trials (CONSORT) and the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines, be adapted to require that researchers clearly state the quality of medicines and any other medical products used in their clinical trials.
In addition, global health bodies should review more closely the current pharmaceuticals market, where globalisation of production, coupled with insufficient regulatory overview, has created a situation where medicines may be of wildly varying qualities.
If the standards aren’t tightened, it is likely that poor quality medicines used in medical research may lead to wrongful conclusions that useful medicines are not useful and that harmful medicines are safe to use.
If these critical amendments are made, the chain of evidence for health policy decision-making should be significantly reinforced, less money on trials will be wasted and patient confidence restored in the quality of medicines being used in clinical trials.
Read the full research findings in the British Medical Journal, and discover more of Paul Newton and colleagues’ work on Antimalarial Drug Quality at the Worldwide Antimalarial Resistance Network (WWARN).