Does data generated by conducting a clinical trial in one region will be applicable or useful for conducting a clinical trial in another region having different environmental condition?
Marie-Christine Reymond • Your question should not find a correct answer without knowing the therapeutic area you deal with. For example, it is well known that cardiovascular risk factors are different from US and European subjects, so that your conclusive findings can not directly be derived between both. Hope it helps.
Satish Champaneria • Environmental conditions are didderent from region to region..and so does conditions and various factors..extrapolation of clinical trials will depend on segment of trials..dosage and other factors will have to be born in mind..
Lynda Cedar • @Kunal: In any case all the clinical data obtained must be included in the study file at the submission, mainly when the action (see the question) was not planned at the beginning of the study....and it would be helpful if you tell us the reason to change the region.
In general it is certainly helpful to have clinical (pharmacology) data and explore, design next studies. Examples: don't we go into first-in-man studies based on the data obtained in animals? Are not the data of international studies (late stage) pooled to complete the study?
Pooling the data obtained by different sites or in different regions, that cannot be generalised, further information is requested, clinical research is not white or black, most of the time grey zones come up, and therefore clinical and medical judgements apply.
What is the different environmental condition: is it genetic? Is it the life style; is it the culture of clinical research? Etc,
What are regions A and B?
What is the medication (therapeutic area)?
What is the stage of the clinical study?
Etc.,
Etc.,
At least for economic reasons: If not a large population is needed, try to run a pilot study (a sample) in the second region and then compare to the data obtained initially.
Dennis McHugh • Many examples including analgesia, infectious diseases, gastroenterology, anti-coagulation, cardiovascular medicine support the fact that populations respond differently. Genetics, environment, standard of care, and even subject expectations all conspire to effect outcomes. Even in the US where everyone came from somewhere else at some point and you might anticipate a degree of homogenization, there are regional differences. Multi-center trials combined with sufficient torturing of the data 'till it yields the "right" answer is the only way to go.
Lynda Cedar • Dennis, my understanding of the question is that data were obtained at site(s) in one region and the sponsor wants to continue the study in another region. You are right, Phase III studies involve different populations (that is even a FDA requiremnent: 18y and up, different gender, different race, style of life, etc.) and mainly when rare diseases are concerned, however, when changes happen in clinical conduct at the middle or at the end of study, there is no general answer, it should be taken case per case, andappropriate recommendations might be provided.
Kunal Desale • Thanks to all of you,
for all of your reference I want to repeat my question with example,
I wanted to know that, does data generated by conducting a Dermatological trial in one region ( e.g. European region) will be useful for conducting a clinical trial in another region ( e.g. Asian region) and if it is useful or applicable then, should sponsor have to conduct only BABE study or whole clinical research of same molecule in another region...???
hope you all get my point.
Dr. Akhilesh Sharma • Clinical Data generated from a region for dermatology study would be suggestive of its efficacy and safety in the concerned population. It would also provide inputs about the dugs efficacy and safety. However, it may not be plausible to extrapolate this data for another region(unless the other regions are part f multi-centric study and the differences in response outcome are included while powering the study and calculating sample size). Clinical situations and factors for a dermatology disease can vary e.g. for acne or psoriasis in Europe exacerbations are seen twice a year mostly during winter & when sunshine is inadequate. The seasons in Europe are different and vary in intensiy, for example as compared to Asian countries like India and China, so disease prognosis/outcome/remissions differs. Similarly, other factors like food habits, skin-cleansing etc also contributes to the prognosis of a disease in skin condition. Nevertheless, data generated in a region is good indicator if not confirmatory of what can be expected from a drug in terms of its efficacy & safety. On the other hand certain skin conditions which have a heavy immune and genetic involvement, the outcome becomes more predictive about the response of a drug in a captive genetic population rather than regional, though careful interpretations are required because genetic variations exist between regions and ethnic groups as we all know e.g. outcome of Gefitinib in Head & Neck cancer in US & Europe as compared to caucasians.
So as stated by Lynda multi-centric, multi-national studies are sufficiently powered enough to look at these differences. In case a study has been completed and results analysed for a region and if another region was not a part of the study but data is required in this 'another' region a proper statistical powering of the study is required based on endpoints to be evaluated and therefore the number of patients is based on the expected outcome in that population/group. This may be a full fledged phase of a clinical trial, however the sample size calculation becomes more easy (and sample requirement 'maybe' less) from the response seen in clinical trial conducted in another region. These are indicators more towards phase IIb/ III studies, I am not sure as to which phase of the clinical trial is being referred to here.
Lynda Cedar • Since it is about a bioequivalence study, the efficacy was demonstrated at the time of developing the original. Depending on how the comparison is assessed, via PK data, PD data or visual scale. If PK data or measurable PD data cannot be obtained, therefore it is about therapeutic bioequivalence. In fact, there is a difference (physiology - ADME) between Caucasian, Asian and black, and a population might be more or less receptive/sensitive to the treatment consequently.
I recommend a pilot exploratory clinical study and then do the adjustment as/if needed. Also, check about the local regulations, whether foreign clinical data can be used or not.
Anders Fuglsang • In a BE trial the primary endpoint is the T/R ratio. While regional differences in phenotype might affect drug response or PK for any given molecule, the T/R ratio or the variability associated with it might not be affected. This is why BE done on population X is often acceptable for a claim in population Y.
It needs to be said though that a good design in population X might need to be tweaked somewhat if the trial for some reason is to be repeated in population Y. Example: Blood sampling regimens in BE trials often need to be planned so that AUCt is 80% or more of AUCinf. Therefore, if population Y is on average (or median) more slowly metabolizing than population X, the timing of blood samples should reflect this.
A similar consideration might apply to equivalence in terms of PD.
Best regards,
A.
Lynda Cedar • Anders, that true if PK or PD data are possible to be measured. This is a dermatology study; the data might be observational, example: heeling, less lesions, decreasing of redness or size, itching, wrinkles, spots, etc.
Francois Peterlongo • The general question was thoroughly debated at the beginning of the ICH process. It was even a serious obstacle to the harmonization between the 3 ICH regions. I remember that Japan authorities were especially reluctant to accept that clinical trials results observed in western populations could be adequate to support product registration for Japanese population.
Fortunately, a consensus was finally found on scientific basis, ans it is the content of the guideline ICH E5 "Ethnic Factors in the Acceptability of Foreign Clinical Data". As far as I know, it is still the reference text about this question.
Lynda Cedar • Yes François, I was at school by the time of process of mutual recognition.
Sponsor still have some difficulties I think when importing data obtained outside the 3 ICH regions.
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