Drug development and marketing

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. 

 

Reducing failure rates

It can be seen from the figure above that the vast majority of candidate molecules identified by the drug discovery process fail to make it to approval. The reasons behind the attrition rate are varied, but one of the major obstacles is the failure of preclinical models systems to accurately predict efficacy in humans. To overcome this, drug development teams are looking to more recent scientific advances to provide the key evidence required to select the most favourable molecular targets and indications to focus on, to more likely culminate in a successful drug approval.

Genome-wide association studies (GWAS) and whole-genome and whole-exome sequencing studies have provided great insight in to identifying the genes that influence human health and disease. The development of statins for dyslipidemia and drugs for rheumatoid arthritis are both examples of how an association between genes (and their variants), a disease and biological data sets can provide insight into disease pathogenesis and guide drug discovery (PMID: 19060906, 24390342). After analysing thousands of genetic associations with disease phenotypes and clinically successful drug mechanisms using a bioinformatics strategy, Nelson et al. (2015, PMID: 26121088) have confirmed that this approach has the potential to double the success rate for the development of new drugs.

Patents

Patents are used to provide legally enforceable protection of intellectual property. In the pharmaceutical industry patents provide the owner with the right to exclude others from making, using or selling their invention for a period of 20 years. Patents are generally applied for very early in the development process, and given that it can be more than 10 years (at best) before the subject of the patent reaches the market, the amount of remaining patent protection (known as the effective life of the patent) is much less than the original 20 years.

This is a narrated slide-set comprehensively covering drug development and regulation, presented at a level for first year medical students. Authored by Prof. Simon Maxwell, University of Edinburgh (s.maxwell@ed.ac.uk).

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Paediatric drug development

The use of drugs in those aged 0-19 years is not generally assessed during the development of biopharmaceuticals, primarily because of the vulnerability of paediatric patients and the need to provide additional safeguards if they are to be included in clinical research. Such practicalities (additional expenses) are often at odds with a drug company’s need to generate a return on its investment. Historically this meant that many medicines were not studied adequately in children, leading to difficulties for prescribers and pharmacists treating children. To ensure that adequate data can be gathered to support the safe and effective use of drugs and biological agents in this group, measures have been established so that children can be protected through the research process.

A slide set provided by the US FDA covering the recommended pathway for developing drugs for use in pediatric patients.

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The use of drugs in those aged 0-19 years is not generally assessed during the development of biopharmaceuticals, primarily because of the vulnerability of paediatric patients and the need to provide additional safeguards if they are to be included in clinical research. Such practicalities (additional expenses) are often at odds with a drug company’s need to generate a return on its investment. Historically this meant that many medicines were not studied adequately in children, leading to difficulties for prescribers and pharmacists treating children. To ensure that adequate data can be gathered to support the safe and effective use of drugs and biological agents in this group, measures have been established so that children can be protected through the research process.

This web page provides access to European legislation covering the research and development, marketing authorisation and post-authorisation phases of pediatric drug development.

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