Tackling the problem of poor quality medicines used in clinical trials

The growing threat of poor quality medicines is a greatly neglected health issue, especially in lower and middle income countries where the problem is most prevalent. Poor quality medicines are categorised into substandard medicines - caused by errors during the manufacturing process - and falsified medicines – caused by criminal fraud. The consequences of poor medicine quality include: prolonged sickness, treatment failure, side effects, loss of income, emergence of drug resistance, increased healthcare costs, and death.

Clinical trials are not immune from the threat of poor medicine quality. Clinical trials are expected to be a trusted method of providing the evidence needed to determine whether medicines are safe, work well and are cost effective. Many global and national healthcare policy decisions are made based on the results from clinical drug trials.

Early in 2015, WWARN's Head of Medicine Quality, Prof Paul Newton, and colleagues published important recommendations in The British Medical Journal. The paper reviewed the quality of medicines used in clinical trials, and suggested that tighter guidelines are needed to ensure that these drugs are carefully monitored and all drugs meet expected standards and show no evidence of deterioration.

“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,” says Prof Newton. “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.”

The paper referred to several instances of poor quality medicines being used in clinical trials. A study of the antimalarial drug sulfadoxine-pyrimethamine in pregnant women in Africa was planned using four locally available brands; one of the brands was found to contain less than 90% of the manufacturer’s stated amount of sulfadoxine.

A study comparing the safety and efficacy of low dose versus high dose vitamin A supplementation was undertaken with young Tanzanian infants. Thirteen months into the trial it was found that the amount of vitamin A in the supplement had deteriorated to only 32% of the stated amount, despite appropriate storage conditions.

Perhaps surprisingly for some, the team found that the issue is not just confined to lower and middle income countries. 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.

“If the standards aren’t tightened, it is likely that poor quality medicines used in clinical research may waste time and resources, provide misleading conclusions, cause adverse events in patients, or inappropriately inform public health policy,” adds Prof Newton.

Prof Newton will present on the topic of ‘Poor medicine quality in clinical trials – hidden troubles?’ in a symposium dedicated to the subject of falsified and substandard medicines at this year’s American Society of Tropical Medicine and Hygiene 64th Annual Meeting.

This symposium will also address: new technologies for identifying falsified medicines, field innovations for defining their prevalence, and the broader policy implications that require governments' attention. The speakers will also provide recommendations for model international regulations and a governing entity to take sustainable corrective action against those involved in the sale of poor quality medicines.

“Poor-quality medicines, whether substandard, degraded or falsified, have far-reaching consequences,” says Prof Philippe Guérin, WWARN Director and Co-Chair of the symposium. “In order to respond to such issues, we need to better understand the scale of the problem and the most affected areas, and raise adequate awareness with all stakeholders. The solution to the problem can only come from collaborative work between governmental authorities, pharmaceutical suppliers, healthcare professionals, and research institutions.

“In the context of clinical trials, we need to work together to ensure that clinical practice guidelines include a requirement to determine and state the quality of drugs used in all studies. We also need to factor the cost of appropriate analyses into grant applications, and ensure that grant awarding bodies insist on the use and documentation of quality assured medicines.”

• Tuesday 27 October, 8:00-9:45 ‘The Pandemic of Falsified and Substandard Medical Products: Detection Techniques and Policy Recommendations’

Location: Marriott - Grand Ballroom Salon H

Publication details:

Newton et al. Quality assurance of drugs used in clinical trials: proposal for adapting guidelines. British Medical Journal. February 25 2015.DOI 2015;350:h602