Market entry, power, pharmacokinetics: what makes a successful drug innovation?

Depending on the timing of market entry, radical innovations can be distinguished from incremental innovations. Whereas a radical innovation typically is the first available derivative of a drug class, incremental innovations are launched later and show a certain benefit compared with the radical innovation. Here, we use historical market data relating to pharmacokinetic (PK), pharmacodynamic (PD), and other drug-related properties to investigate which derivatives within certain drug classes have been most successful on the market. Based on our investigations, we suggest naming the most successful drugs 'overtaking innovation', because they often exceed the market share of all the other derivatives. Seven drug classes showed that the overtaking innovation is never a radical innovation, but rather an early incremental innovation, with advantages in manageability and/or tolerance.

Herbal medicinal products - Evidence and tradition from a historical perspective.

BACKGROUND: Aside from the fully licensed herbal medicines there are products on the European pharmaceutical market which are registered by virtue of their longstanding traditional use. The normal registration procedure does not apply to them because presently they do not meet the legal requirements for a full license as set out in the relevant European Union Directive. One of these requirements, "proof of tradition", has so far been dealt with in different ways and fails to meet the criteria of good practice. METHOD: This analysis is based on a selective literature search in PubMed and in databases of medical and pharmaceutical history, interviews with licensing experts, a consensus meeting attended by researchers with a background in general medicine, phytotherapy, medical and pharmaceutical history, biometry, ethnopharmacology, pharmacognosy and the pharmaceutical industry. RESULTS AND DISCUSSION: The 2004 EU Directive, which governs the registration of Traditional Herbal Medicinal Products and demands proof of tradition, is a regulatory construct and, above all, the outcome of a political process that has ended in a pragmatic compromise. The concept of tradition applied in the Directive does not sufficiently reflect the semantic breadth of the term. The only condition defined is that a specific commercial preparation needs to have been on the market for 30 years (15 of them inside the EU). Such an approach does not make full scientific use of the evidence available because the information excerpted from historical sources, if adequately processed, may yield valuable insights. This applies to indications, modes of application, efficacy and product safety (innocuousness). Such criteria should enter in full into the benefit-risk-analysis of applied preparations, in the registration process as well as in the therapeutic practice. CONCLUSION: When registering Traditional Herbal Medicinal Products the criterion of evidence-based medicine will only be met if all the facts available are assessed and evaluated, over and above the formally stipulated regulatory provisions (30 years, product reference). To this end, the scientific methods (from among the natural, life or cultural sciences), which are recognized as authoritative in each case, must be applied.

The botanical explorer's legacy: a promising bioprospecting tool.

Records about the traditional uses of medicinal plants can be considered useful in bioprospecting (i.e., the search for new active agents or lead structures in nature). Several sources like Egyptian papyri, early modern herbals and pharmacopoeias have been studied in this respect. It is proposed to use recordings of botanically interested explorers of the 19th and early 20th centuries as well. Some of them give detailed information about traditionally used medicinal plants and analysis shows that a considerable number of these have never been scientifically investigated. Existing studies, however, are confirming the traditional uses described to a great extent. Thus, the explorer's writings should not be neglected while looking for starting points for plant screening; success seems more likely than with screening at random.

Xysmalobium undulatum (Uzara) research- how everything began.

ETHNOPHARMACOLOGICAL RELEVANCE: Xysmalobium undulatum (Uzara) is a traditionally used medicinal plant from South Africa. It found its way into European research in the early 20th century and is widely used as a remedy against diarrhoea. The purpose of this study was to explore the circumstances of knowledge transfer and early research into phytochemistry and therapeutic potential of Xysmalobium undulatum. RESULTS: The drug was brought to Europe through a former soldier, Wilhelm Heinrich Adolph Hopf (1887-1929). Some details about his life are provided here the first time, as well as some aspects of early research on the drug, which has mainly been done at the University of Marburg, Germany.

Traditional use of medicinal agents: a valid source of evidence.

Traditional knowledge uncovered by serious historical research may help to identify new therapeutic agents. It also plays a part in safety evaluation and drug regulation. So far, however, this way of gaining knowledge is very much neglected in the concept of evidence based medicine, which is in no way contradictory to traditional use. Thus, the true meaning of the word 'tradition' is described, while reliable historical sources are quoted. It is then shown how research into the traditional use of medicinal plants is able to reveal knowledge about efficacy and safety of natural products. Several examples successfully leading to new therapeutic options are given. It is then referred to the concept of 'social validation' developed by the Canadian medical historian John Crellin, who also established guidelines for respective research. Eventually, it is proposed to modify the list of evidence levels by inserting an evidence level 4b 'Traditional use in more than one regional cluster'.

[Traditional use: phytopharmaceuticals seen from a historical perspective]. / Traditionelle Anwendung: Eine Betrachtung zu pflanzlichen Arzneimitteln aus pharmaziehistorischer Sicht.

In phytopharmacy, the term 'traditional use' is widely found in colloquial language but has also great significance for registration procedures of medicinal products. It is therefore justified to explore its actual meaning from the perspective of social and pharmaceutical history. It is shown that a tradition is founded by transmission of knowledge and techniques over at least three generations, while the life span of a generation may vary widely. Changes and adaptations to technical advancements do not at all avoid but even constitute the development of traditions. Historical research provides valuable knowledge about effectiveness and risk of phytopharmaceuticals. Criteria of traditional use may complement but not substitute modern evidence based methods; however they always need to be applied historically sound.

Endermatic, epidermatic, enepidermatic-the early history of penetration enhancers.

Already at the end of the 18th century, attempts were made to administer drugs transdermally. Several techniques were applied, including rubbing drug substances into the intact or wounded skin. Penetration enhancers were investigated as well, including human and animal body fluids, in particular gastric juice and saliva. In the 19th century, lipophilic solubilizers like chloroform and ether were tried. Although the experiments were mostly done against a pre-rational background some may be worth to be judged under scientific premises.

[Occult medicine in the 20th century: pharmacotherapy by Demeter Georgievitz-Weitzer, known as Surya (1873 - 1949)]. / Okkulte medizin im 20. Jahrhundert: Pharmakotherapie nach Demeter Georgievitz-Weitzer, genannt Surya (1873-1949).

Demeter Georgievitz-Weitzer (1873-1949), called "Surya", Sanskrit for "sun", was an important representative of medical occultism in the first half of the 20th century. He worked as a journal editor and published a 13-volume book series about occult medicine, mainly written by himself. His hypotheses were closely related to the "Lebensreform" movement around 1900. Regarding diagnostics, he relied on astrology, cheiromancy, and clairvoyance, while therapeutics were dominated by diet and spagyric remedies according to Cesare Mattei (1809-1896) and Carl-Friedrich Zimpel (1801-1879). In his later years, he developed his own healing system, initially comprising eight, later only two preparations. Surya remedies were commercially available until the end of the 20th century,

Beans and diabetes: Phaseolus vulgaris preparations as antihyperglycemic agents.

Bean pods (Phaseolus vulgaris) are among the most widely used traditional remedies against diabetes mellitus. Historical knowledge is summarized and compared to recent study results. Reports dating from the first half of the 20(th) century as well as recent publications show contradictory results. It seems that Phaseolus preparations should not be considered the first choice in phytopharmaceutical treatment of diabetes or lead structure research. To be effective, fairly high doses of aqueous extracts need to be given. Because of their fiber content and an alpha-amylase inhibitory effect, beans might be more useful as food components in preventing or ameliorating type 2 diabetes.

Centennial of intravenous regional anesthesia. Bier's Block (1908-2008).

The surgeon August Gustav Bier significantly influenced surgery, general medicine, and especially anesthesia. He was the father of spinal anesthesia (1898) and intravenous regional anesthesia (1908). Both anesthetic techniques are still valuable and widely applied in everyday anesthesia practices throughout the world, with a high degree of safety, efficacy, efficiency, and satisfaction. On the occasion of the centennial anniversary of the first use of intravenous regional anesthesia it is appropriate to recall Bier's contribution to the repertoire of anesthesiologists. The evolutionary history of both the injected drugs and the refinements of the technique are elaborated upon.

[Wilhelm Heinrich Schüssler's healing system "Biochemie" and its further development by Dietrich Schöpwinkel]. / Das "biochemische" Heilverfahren nach Wilhelm Heinrich Schüssler und seine Weiterentwicklung durch Dietrich Schöpwinkel.

The German Physician Wilhelm Schüssler (1821-1898) developed a healing system called "Biochemie". Basically it had merely the character of a substitution therapy with mineral compounds and was based on physiological considerations by Jakob Moleschott (1822-1893) and Justus von Liebig (1803-1873) which were fundamental for the development of the scientific discipline of biochemistry as well. Schüssler himself, however, who had been educated in homoeopathy, introduced more and more immaterial or "biodynamic" explanations for the therapeutic effect of the mineral salt preparations. This attempt was continued by his successors, namely by Dietrich (called Dieter) Schöpwinkel (1876-1946) who enriched the system with new preparations as well as several theoretical aspects strongly related to the dynamic approach.

[Mild radium therapy: radiation medicine-, life-, body- and personal hygiene remedies in the first half of the 20th century]. / Die Radiumschwachtherapie: Strahlende Arznei-, Lebens- und Körperpflegemittel in der ersten Hälfte des 20. Jahrhunderts.

During the first half of the 20th century numerous drugs, foodstuffs and cosmetics were brought on the market, whose supposed effects were explained with their weak radioactivity. Their subtle radiation was believed to stimulate the vital forces of the body, thus leading to recovery from illness, or to an improvement in beauty and to rejuvenation. Among others, bath and drinking waters enriched with radioactive materials were advertised for this purpose. The then known radioactive medicines included preparations of healing earth, the so-called Salus-Oil, the TRUW preparations, and "Radithor", which was popular in the United States. There were also radioactive foodstuffs (butter, chocolate, rusk) and cosmetics. This mild radiotherapy may be characterised as a form of bio-dynamistic healing.