The US Food and Drug Administration, the European Medicines Agency, and other experienced regulatory agencies have stringent pharmacovigilance programs that ensure monitoring of drug quality and usage, efficacy, adverse events, and other post-marketing concerns. These programs, supported by both government and innovator pharmaceutical funding, are essential to detect, assess, communicate, and assure “real world” drug safety and efficacy. Post-marketing drug withdrawals such as Vioxx® demonstrate post-marketing drug safety monitoring success in saving lives and preventing morbidity. Pharmacovigilance is critical for revising drug product labeling; detecting harm due to inappropriate use, counterfeit, and substandard medicines; crafting treatment guidelines; communicating new or reinforced information to medical professionals and the public; and, not least, providing advice on pharmaceutical action to clinicians.
But the scope of global pharmacovigilance programs is not on par with the distribution of the drugs intended to be monitored. The introduction and scale up of low cost generic antiretroviral drugs (ARVs) in resource limited settings (RLS), for example, has not been accompanied by comparable global pharmacovigilance. As of 2010, more than 6 million people worldwide had been provided with ARVs, an effort that has been largely sustained by the US government, the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund), and other donors. But with increased access comes a greater need to monitor and promote the safety and effectiveness of these essential medicines in the new environments, which are distinct from those of pre-market studies and the resource rich countries that have had ARV access for years. Without sufficient monitoring systems in place, we can’t efficiently identify and stop counterfeiting of ARV drugs.
Unfortunately, not all RLS have the structures, systems, or resources necessary to support medicines safety activities. Notwithstanding substantial work and individual efforts from such organizations as the World Health Organization (WHO), the WHO-Uppsala Monitoring Center (WHO-UMC), Management Sciences for Health-Strengthening Pharmaceutical Systems (MSH-SPS), academic centers, RLS Ministries of Health, and the US National Institutes of Health (NIH), much remains to be done.
A recent conference held by the Forum for Collaborative HIV Research (Forum) in Washington, DC, and an associated publication in PLoS Medicine discussed impediments and potential solutions to the implementation of sustainable global pharmacovigilance. In the near term, the Bill and Melinda Gates Foundation (BMGF) and the European Commission under its Framework Programme Seven have supported investigations into options. Technical expertise has been and will continue to be provided by WHO, WHO-UMC, NIH and MSH-SPS. In particular, the BMGF and WHO have provided guidance on including pharmacovigilance in countries’ proposals for funding that have been submitted to the Global Fund for building national health infrastructure for HIV/AIDS efforts. Correspondingly, the organizations have also provided technical support to the Global Fund in their analysis of these applications, 79 of which included pharmacovigilance in their proposals last year. Global Fund support may be flat in total expenditures but those monies are significant and will be available for the long-term. Efforts must also go beyond HIV/AIDS focus and lead to overall pharmacovigilance system strengthening.
The PLoS article and the Forum roundtable also highlighted a potential new vision for sustainable global pharmacovigilance that could build on these currently available resources. While global pharmacovigilance must ultimately be the responsibility of individual nations, a global system in which each country provides its own system will not work universally, if only because some countries will lack sufficient healthcare infrastructure for the foreseeable future. Regional collaborations may be one option. Alternatively, public-private partnerships could be established nationally, regionally or even globally, with funding from international donors as well as pharmaceutical companies that could also contribute technical support. Experienced regulatory systems could expand their enforcement domain beyond country borders to include requirements for, and agency review of, international data collection, analysis, and reporting by pharmaceutical companies. This might be done at little additional cost—an extension not dissimilar to the extra workload undertaken for tentative approvals of foreign generic drugs that is supported by the US President’s Emergency Plan for AIDS Relief (PEPFAR). Under that system, the US government provides funds to FDA for its review of manufacturing and labeling compliance of generics intended for use outside the United States. Further, there is a critical need for the development of metrics to evaluate the success and effectiveness of various new models of pharmacovigilance.
Reporting also requires the time of healthcare givers. Currently, the physician-to-population and the pharmacist-to-population ratio may be too low to sustain adequate data collection to support pharmacovigilance. Simplified reporting systems exist and their implementation is underway, but these may still be too cumbersome or not able to generate data that are needed for comprehensive analysis. Other alternatives include use of community workers rather than healthcare givers. Indeed, direct patient feedback currently represents a third of US pharmacovigilance reports.
Sustainable global pharmacovigilance requires re-thinking how reports of patient events around the world can be generated, coded, and analyzed but the future of safe and effective medicines requires it.
Jur Strobos is the deputy director of the Forum for Collaborative HIV Research. Andy Stergachis is a professor of epidemiology and global health and director of the Global Medicines Program at School of Public Health at the University of Washington.