Drug development and marketing
When a new drug has been discovered it goes through a development process that aims to deliver sufficient evidence for it to be granted a marketing authorisation (‘license’) by the relevant regulatory authority. This process takes over 10 years and may cost up to $1bn. The development pathway has traditionally included a preclinical phase followed by four clinical phases, shown diagramatically below.
- Phase I studies involve initial single dose ‘first-into-man’ studies followed by repeated dose studies. They aim to establish the basic pharmacokinetic (absorption, distribution, metabolism and excretion) and pharmacodynamic (beneficial and adverse effects) properties, and short-term safety.
- Phase II studies investigate clinical effectiveness (‘proof of concept’), safety and dose-response relationship, often with a surrogate clinical endpoint, in the target population to determine the optimal dosing regimen for larger confirmatory studies.
- Phase III studies are large, expensive clinical trials that confirm safety and efficacy in the target patient population, using relevant clinical endpoints. They may be placebo-controlled studies or comparisons with other active compounds. In comparative studies the intention is usually to demonstrate superiority or, at the very least, non-inferiority. So-called ‘real-life’ trials involve a comparison of the new agent with standard therapy; such trials often include a pharmacoeconomic assessment of the added value that a new treatment brings in relation to its cost. Phase III studies are critical because they yield much of the information on which the regulatory approval will depend.
- Phase IV studies are undertaken after marketing has begun and evaluate new indications, new doses or formulations, long-term safety or cost-effectiveness.
The marketing activities of the pharmaceutical industry are well resourced and essential in the process of recouping the massive costs of development. In some countries such as the US it is possible to promote a new drug by direct-to-consumer advertising although this is illegal in the EU countries. There are still opportunities to influence consumers via product placement within ‘news’ stories, resources given to patient support groups and online infiormation. A major focus is on promotion to prescribers via educational events, sponsorship of meetings, adverts in journals, involvement with opinion leaders, and representatives with glossy leaflets. Such largesse has the potential to cause significant conflicts of interest, and might tempt prescribers to favour one drug over another, even in the face of evidence on effectiveness or cost-effectiveness. Interactions with the industry now much more tightly regulated than in former times but there are still abuses.