In our country, approval for a clinical trial of a drug is issued by the national expert organization in the field of drug circulation (which is an analogue of the FDA, EMA and issues approval for conducting clinical trials of drugs) and the National Bioethics Commission.
Currently, a situation has arisen that the national expert organization refuses to issue approval for a clinical study of a combination of drugs. It refers to the fact that this is scheme of treatment (i.e. a treatment method) and not a drug. Is it necessary to obtain the approval of a national expert organization for the circulation of medicines (analogous to the FDA, EMA in a country) for a clinical trials of a combination of drugs, or in this case, the approval of the National Bioethics Commission is enough? Or is it necessary to obtain the approval of another expert organization?
I do not know the regulation of your country so I cannot answer completely. However if the two drugs you want to test in combination are on the market already and there are no concerns regarding potential negative interactions you may need to ask for local ethics committee approval only. If one of the two is on the market and the other is under development you may ask central authorization for this drug added to a standard therapy (if this is the case), hence you are asking authorization for a specific drug.
When two drugs are combined, they behave like the third drug, for better, for worse, or no difference, regardless whether they are approved or not yet approved. The scientists or the pharmaceutical companies need to prove they are synergism (CI1) quantitatively, at least in vitro. Preferentially, also in animals, although these will be costly, time consuming, and require exploratory studies for optimal conditions for the study/trial plan, e.g., dose range, dose density, formulation, route, and schedule.
It is un-scientific and un-ethical to use human as the guinea pig! We shall use this century's quantitative , computerized technology. (see Chou TC, Pharmacol. Rev. 58: 621-681, 2006, as of 1.25.2020; cited 3,347 times in 965 biomedical journals worldwide).
The approval of the national authorities is mandatory in any country if the trial is supposed to be conducted according to the current regulations, I believe. Why they refuse to approve the combinations, it's a fair question I am not able to answer. There's e.g. EMA Guideline on clinical development of fixed combination medicinal products (EMA/CHMP/158268/2017) which indicates what types of trials are needed to be performed with the combinations.
The problem is current global biomedical communities, including, FDA and NIH are still focusing on PK based R&D, mainly for specific diseases, specific organs or specific drugs, and grossly neglecting the more basic General Principle of Pharmacodynamics (PD) which is well developed, as indicated in above, Chou TC, Pharmacol. Rev. 59: 621-681, 2006 article. As the results of this deficiency, most biomedical scientists still do not define "PD" , or the dose-effect curve basic dynamic principle. Do not understand "What is the additive effect of two drugs? or more drugs combos?", "What is the mathematical definition of Synergism?" , "What is the Synergy quantification equation, algorithm for automated computer simulation (in 1-2 seconds), using very small number of dose-data points, in cells, in animals and in clinical protocol design, for automated data simulation and analysis?" This is a sad and confusing situations everywhere. This is why I advocate for a modernization, reform with the new e-technology, and cost-effective , efficient , digital R&D and drug -valuation guidance. (For more information, please visit my web sites in Google Scholars -Ting-Chao Chou, Web of Science, Wikipedia. or www.combosyn.com). Update PDF illustrative summary slides are frequently available in the above references. 2.26.2020. 10:05AM
dear Vitaliy, bioethics commissions do not approve clinical trials, nor do they have the authority to give the green light for the initiation of research. The role of the IRB is consultation; their decisions are not binding but are used for the final decision-making of the corresponding maximum authority. That is a common mistake that many people still do not fully understand.
I give you an example, if you work for Institute "X" your project must be approved by the Dean of the Institute X or the commission assigned by the Dean for that purpose. The Dean requires the opinion of the bioethics commission to make a decision, however, the decision rests with the dean. In summary, you should look for the mechanisms to obtain the necessary permits from the highest authority in that area in your country.
What is expert or authority? International FDAs and NIH, and majority on biomedical scientists, still do not understand the Definitions of “PD” , “Synergy” and “Addititve of TwoDrugs”! Do you understand? If not, please read Chou TC, Pharmacological Rev. 58: 621- 681, 2006, or visit www.combosyn.com. Thanks.
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