The phrase «drug design» is to some extent a misnomer. A more accurate term is ligand design (i.e., design of a small molecule that will bind tightly to its target). Although modeling techniques for prediction of binding affinity are reasonably successful, there are many other properties, such as bioavailability, metabolic half-life, side effects, etc., that first must be optimized before a ligand can become a safe and efficacious drug. These other characteristics are often difficult to predict using rational drug design techniques.

The Human Genome Project was declared complete in April 2003. An initial rough draft of the human genome was available in June 2000 and by February 2001 a working draft had been completed and published followed by the final sequencing mapping of the human genome on April 14, 2003. Although this was reported to be 99% of the human genome with 99.99% accuracy a major quality assessment of the human genome sequence was published on May 27, 2004 indicating over 92% of sampling exceeded 99.99% accuracy which is within the intended goal. Further analyses and papers on the HGP continue to occur.

The sequencing of individual genomes further unveiled levels of genetic complexity that had not been appreciated before. Personal genomics helped reveal the significant level of diversity in the human genome attributed not only to SNPs but structural variations as well. However, the application of such knowledge to the treatment of disease and in the medical field is only in its very beginnings. Exome sequencing has become increasingly popular as a tool to aid in diagnosis of genetic disease because the exome contributes only 1% of the genomic sequence but accounts for roughly 85% of the disease causing mutations.

Although knowing the true extent of systemic absorption (referred to as absolute bioavailability) is clearly useful, in practice it is not determined as frequently as one may think. The reason for this is that its assessment requires an intravenous reference, that is, a route of administration that guarantees that all of the administered drug reaches the systemic circulation. Such studies come at considerable cost, not least of which is the necessity to conduct preclinical toxicity tests to ensure adequate safety, as well as there being potential problems due to solubility limitations. These limitations may be overcome, however, by administering a very low dose (typically a few micrograms) of an isotopically labelled drug concomitantly with a therapeutic non-labelled oral dose. Providing the isotopically-labelled intravenous dose is sufficiently low so as not to perturb the systemic drug concentrations achieved from the absorbed oral dose, then the intravenous and oral pharmacokinetics can be deconvoluted by virtue of the their different isotopic constitution and thereby determine the oral and intravenous pharmacokinetics from the same dose administration. This technique eliminates pharmacokinetic issues on non-equivalent clearance as well as enabling the intravenous dose to be administered with a minimum of toxicology and formulation. The technique was first applied using stable-isotopes such as C-13 and mass-spectrometry to distinguish the isotopes by mass difference. More recently, C-14 labelled drugs are administered intravenously and accelerator mass spectrometry (AMS) used to measure the isotopically labelled drug along with mass spectrometry for the unlabelled drug.

The sponsor and the local site investigators are jointly responsible for writing a site-specific informed consent that accurately informs the potential subjects of the true risks and potential benefits of participating in the study, while at the same time presenting the material as briefly as possible and in ordinary language. FDA regulations and ICH guidelines both require «the information that is given to the subject or the representative shall be in language understandable to the subject or the representative.» If the participant’s native language is not English, the sponsor must translate the informed consent into the language of the participant.

The number of human protein-coding genes is not significantly larger than that of many less complex organisms, such as the roundworm and the fruit fly. This difference may result from the extensive use of alternative pre-mRNA splicing in humans, which provides the ability to build a very large number of modular proteins through the selective incorporation of exons.

Epigenetics describes a variety of features of the human genome that transcend its primary DNA sequence, such as chromatin packaging, histone modifications and DNA methylation, and which are important in regulating gene expression, genome replication and other cellular processes. Epigenetic markers strengthen and weaken transcription of certain genes but do not affect the actual sequence of DNA nucleotides. DNA methylation is a major form of epigenetic control over gene expression and one of the most highly studied topics in epigenetics. During development, the human DNA methylation profile experiences dramatic changes. In early germ line cells, the genome has very low methylation levels. These low levels generally describe active genes. As development progresses, parental imprinting tags lead to increased methylation activity.

The full cost of bringing a new drug (i.e. a drug that is a new chemical entity) to market — from discovery through clinical trials to approval — is complex and controversial. One element of the complexity is that the much-publicized final numbers often do not include just the simple out-of-pocket expenses, but also include «capital costs», which are included to take into account the long time period (often at least ten years) during which the out-of-pocket costs are expended; additionally it is often not stated whether a given figure includes the capitalized cost or comprises only out-of-pocket expenses. Another element of complexity is that all estimates are based on confidential information owned by drug companies, released by them voluntarily. There is currently no way to validate these numbers. The numbers are controversial, as drug companies use them to justify the prices of their drugs and various advocates for lower drug prices have challenged them. The controversy is not only between «high» and «low» — the numbers also vary greatly at the high end.

Many clinical trials do not involve any money. However, when the sponsor is a private company or a national health agency, investigators are almost always paid to participate. These amounts can be small, just covering a partial salary for research assistants and the cost of any supplies (usually the case with national health agency studies), or be substantial and include ’overhead’ that allows the investigator to pay the research staff during times between clinical trials.

In the field of drug discovery, classical pharmacology, also known as forward pharmacology, or phenotypic drug discovery (PDD), relies on phenotypic screening (screening in intact cells or whole organisms) of chemical libraries of synthetic small molecules, natural products or extracts to identify substances that have a desirable therapeutic effect. Using the techniques of medicinal chemistry, the potency, selectivity, and other properties of these screening hits are optimized to produce candidate drugs.