Drug Development

Risk in drug development falls into two broad categories:

• Safety risk. All drug treatments are associated with both risks and benefits. Identification of potential risks based on toxicology studies and an understanding of the biology of the target system are important means of signal detection. Any potential risk must be tracked and evaluated in clinical practice. A number of recent high-profile drug withdrawals have been caused by adverse effects were predicted by early phase studies but incompletely evaluated (Fig 13). Even with the best signal detection processes, rare and potentially serious adverse effects of a medicine may not be identified during drug development because of the relatively small number of people studied. Post-marketing safety surveillance (pharmacovigilance) is therefore vital. There can be no simple rules for what is an acceptable risk because this is entirely dependent on the context and benefit. For example, a risk of cardiomyopathy may be acceptable for a treatment for refractory cancer but unacceptable for a drug for mild asthma.
• Financial risk. The second major risk in drug development is the financial risk of continuing to develop something that is not going to be effective. Decision making in early development is commonly based on surrogates and biomarkers, whereas endpoints in pivotal (Phase III) trials have become focused on long-term outcome measures. Failure to choose reliable biomarkers can lead to very costly mistakes with apparently impressive Phase II results being followed by negative phase III studies. Even the largest global pharmaceutical companies cannot afford many failures in Phase III and remain financially viable. The ability to make early decisions about the viability of a new therapy and its eligibility for reimbursement by healthcare systems (e.g. insurance companies, national health services) will be critical to successful drug development over the coming decades.