Drug Development – Lessons learnt from HIV and H1N1:
The humankind is constantly reminded of the threat of newly emerging infectious diseases – the declaration by the World Health Organization (WHO) about the global H1N1 flu pandemic in June 2009 is just one example. By the time Dr. Margaret Chan, Director-General of WHO made the announcement, pandemic level of H1N1 had already reached the highest level (level six) and the numbers of confirmed cases were over 30,000.
The world governments and health agencies need to be prepared for responding to such public health challenges by activating the pandemic plans and doing everything necessary to keep the people safe. Scientific expertise across multiple disciplines needs to be used to combat the threat posed by such emerging infectious diseases.
The term emergent disease includes any disease which is previously unknown; increase in incidence of a previously known disease; disease caused by intentional dissemination of biological products by bioterrorists. Some of the infections that have affected the humankind in the recent past are severe acute respiratory syndrome (SARS), avian influenza (H5N1), antibiotic resistant bacterial infections like methicillin-resistant Staphylococcus aureus (MRSA), and viral hemorrhagic fevers.
The factors contributing to the spread of these infections are diverse and may be classified under four broad categories: geno-biological factors; physical and environmental factors; ecological factors; socio-economic and political factors. And not surprisingly, keeping in view the diverse contributing factors, wide ranges of organizations need to be working in tandem to evolve the treatment strategies and solutions. The knowledge gained from the development of treatments for one such emerging disease may help us in developing drugs for other infections. Detecting, preventing, and controlling emerging diseases is thus important because it helps us to be better prepared for the future microbial threats to health. And there can be no better example than the story of Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS).
AIDS was identified as a disease in 1981 and HIV was identified as the cause of AIDS in 1983. Within four years, Zidovudine was developed and was approved as the first anti-HIV drug. Through the years, the treatment of HIV has witnessed dramatic changes-from monotherapy to combination therapy to highly active antiretroviral therapy (HAART). With the evolving treatment strategies, HIV is now considered as a chronic disease rather than a fatal disorder. The invaluable lessons learned during the development of HIV therapies, particularly those involving the application of principles of clinical pharmacology may be applied to other diseases as well. They can be listed as follows:
- Data from multiple drug sponsors could be shared in order to facilitate the validation of a surrogate end point.
- Clear instructions in drug labels and education of physician and the patient may help in managing the complex drug interactions.
- Proper labeling may help in the appropriate use of the drug.
- Patient groups may influence the drug development process leading to fast-track approval of the drugs.
Also, the influence exerted by the patient groups played an important role in the early years of HIV.
There was collaboration across all relevant stakeholders to achieve effective HIV drug development. These initiatives brought together government, industry, and academia, along with patient and community groups, to facilitate and enhance HIV research. The collaborations are continuing even today.
Just like the lessons learnt from the HIV / AIDS experiences, the recent experiences with H1N1 influenza also remind us of the impact of gaps in knowledge regarding the use of a drug product in specific populations. Children under age of two years and pregnant women are listed as the high-risk patient populations by the centers for disease control and prevention (CDC). Unfortunately, drugs approved for use against H1N1 do not have standard dosing instructions for use in these high-risk patient populations.
The development of drugs to treat emerging infections can thus benefit from knowledge gained by clinical pharmacologists in response to HIV and to H1N1 influenza. The clinical pharmacologists need to be building on this knowledge so that they can respond to the opportunities listed above and also to those arising in the future.