In the June issue of Nature Reviews Drug Discovery Aaron Kesselheim and Jerry Avorn from Harvard Medical School in Boston, Massachusetts, published the results of their survey among physicians for the most transformative drugs of the past 25 years (Kesselheim und Avorn, Nat Rev Drug Discov 2013, 12: 425-431). In a structured Delphi process (an established method that iteratively uses structured interviews with repeated input of the participants to reach a consensus) about 180 experts from 30 U.S. academic medical centers in 15 medical specialties were interviewed.
434 agents newly registered in the U.S. between January 1985 and December 2009, which were each assigned to one of 15 specialties, were evaluated. Ultimately, any substance was evaluated by 9-16 experts. The criterion that was most frequently reported as crucial for a high ranking was “improved efficacy”. This was followed in descending order of frequency: “novel mechanism of action”, “impact on practice in field”, “scientific merit”, “improved safety”, “widespread use and impact”, “ease of patient use” and lastly “application to multiple diseases”.
For psychiatry, the selective serotonin reuptake inhibitor (SSRI) fluoxetine was ranked number 1. Two main reasons for this choice were given: “Transformed treatment of depression providing effective agent with far fewer side effects and toxicity risks in overdose than tricyclic antidepressants and monoamine oxidase inhibitors.” (Improved safety). The second reason was: “First SSRI to have a major impact worldwide. Ushered in a novel ear of antidepressants.” (widespread use and impact).
Fluoxetine was closely followed by antipsychotic clozapine. The major reason for this choice was: “Introduced a new set of compounds for treatment of psychosis.” (novel mechanism of action). No other psychotropic had even a marginal role in this expert survey.
With fluoxetine and clozapine, two compounds were selected which have been available for about 25 years in the United States. Fluoxetine was approved in December 1987 in the United States and in 1990 in Germany. Clozapine was approved in the U.S. in 1989. In German speaking countries, the substance was even introduced already in 1972. This fact also symbolizes the crisis in the development of new psychotropic drugs. The developments of the past 25 years are considered only as incremental progress. Interestingly, with fluoxetine a group of drugs (SSRIs) is rated as outstanding innovation, which is classified only marginally effective and possibly hazardous in the lay press (and some professionals) (see also my post of March 7th, 2013).
It must be emphasized here that “improved efficacy” and “novel mechanism of action” are considered as the two by far most important criteria that characterize an innovation. The authors of the article request the pharmaceutical industry to focus their development efforts on substances that meet these requirements.
Here are the first-and second-place substances of all 15 specialties (for some specialties drug classes and not individual compounds were chosen):
- Anaesthesiology: 1) Propofol 2) Remifentanil
- Cardiology: 1) Lovastatin 2) ACE inhibitors
- Dermatology: 1) TNF blockers 2) OnabotulinumtoxinA
- Endocrinology: 1) Bisphosphonates 2) Metformin
- Gastroenterology: 1) Omeprazole 2) TNF blockers
- Infectious diseases: 1) HIV protease inhibitors 2) Zidovudine
- Genetics: 1) Alglucerase 2) Nitisinone
- Nephrology: 1) ACE inhibitors 2) Epoetin alfa
- Neurology: 1) Sumatriptan 2) Interferon beta-1b und beta-1a
- Oncology: 1) Imatinib 2) Rituximab
- Ophthalmology: 1) Anti-VGEF agents 2) Latanoprost
- Psychiatry: 1) Fluoxetine 2) Clozapine
- Pulmonary medicine: 1) Epoprostenol 2) Fluticasone/Salmeterol-Combination
- Rheumatology: 1) TNF blockers 2) Biphosphonates
- Urology: 1) Sildenafil 2) Tamsulosin
This post is also available in: German