Clinical research and drug development of antivirals in HIV: an industry perspective

Clinical research can be viewed from three perspectives: research, patient care, and regulatory. Clinical research strategies can be either drug oriented, following the traditional phase I-II-III flow, or disease oriented. The drug-oriented strategy has as its goal regulatory approval, which means widespread patient-care usage. The disease-oriented strategy focuses on improving the overall care of the disease in question. At times, a dynamic tension exists between the two strategies. In HIV, as in all diseases, industry mainly is involved in drug-oriented studies emphasizing the regulatory perspective. In HIV a critical issue involves accelerated approval, following expanded access, based on surrogate markers. This initial approval is for end-stage therapy (the expanded access population). Additional claims require a full supplemental New Drug Application utilizing clinical end points. This leads to a situation in which the label, over time, becomes less relevant to how the drug is used in actual practice. This has caused concern among the patient advocates and is becoming a major challenge for the industry.