Table 1.
Curriculum vitae. Milestones of clinical research in the career of the first industrial herbal medicinal product containing an extract of Cimicifuga racemosa (CR)
| Year | Milestone | Country/region |
|---|---|---|
| 1956 | Year of birth of Remifemin® | Germany |
| 1956 to 1970s | Documentation of clinical experiences | Germany |
| 1980s | First randomized controlled clinical trials according to 1976 Medicines Act | Germany |
| 1986 | First placebo-controlled clinical trial on iCR | Germany |
| 1989 | German Commission E monograph on CR | Germany |
| 1991 | Good Clinical Practice | Europe |
| 1995 | First clinical dose–efficacy study | Poland |
| 2003 | First placebo-controlled study on another CR extract; MRS-based effect size of hormone therapy (HT) | Czech Republic |
| 2002 to 2005 | Second placebo-controlled study on iCR confirms efficacy, identifies confounders influencing the effect size, first subtle hints of supra-hypothalamic CNS influence | Germany |
| 2005 | Controlled study in comparison to hormone patches | Italy |
| 2005/2008 | Clinical evidence on CNS influence of iCR by PET | USA |
| 2007 | Controlled study in comparison to tibolone, first study in China | China |
| 2007 | Clinical study on iCR safety in breast tissue | Sweden |
| 2007 | Pharmacoepidemiological cohort study on recurrence-free survival after breast cancer | Germany |
| 2010 | Monograph of the Herbal Medicinal Product Committee at the European Medicines Agency concludes well-established use of CR-based medicines for alleviating menopausal symptoms, does not limit the duration of use, allows the use in breast cancer survivors if medically advised | Europe |
| 2011 | Meta-/reanalytic safety comparison of iCR with placebo, tibolone and HT regarding breast density | Sweden |
| 2011 | Meta-analysis on liver safety | Europe, China |
| 2005 to 2015 | More clinical studies on iCR in Europe, America, Asia | International |
| 2012 | Cochrane Report on black cohosh (Cimicifuga ssp.) for menopausal symptoms | Australia |
| 2013 | Corrective reply to Cochrane Report, complete meta-analysis of all nine placebo-controlled studies on efficacy | International |
| 2013 | Systematic review on efficacy (18 studies) and safety (35 studies); conclusive evidence on efficacy if of licensed product quality | Germany |
| 2014 | Supplementary benefit in myoma patients | China |
| 2015 | Most recent placebo-controlled study; improvement of sleep quality | China |
| 2016 | Anniversary. 11,073 patients in 28 clinical studies on efficacy since 2000 (10,883 investigated with a medicinal product of licensed quality, 89% thereof iCR) | Total |
iCR isopropanolic CR extract, MRS Menopause Rating Scale, CNS Central nervous system, PET Positron emission tomography, HT Hormone therapy