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YT ☆ Thailand, 2009-09-23 20:52 (5708 d 02:35 ago) Posting: # 4239 Views: 8,957 |
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Dear all, Nice to be a member here. I am working at a BE center located in Thailand as pharmacist and some part as project coordinator. There are some issues rested from time to time because our company is quite new in this business. I'd like to explain to you some situation. Any comment, suggestion and opinion are appreciate for more understanding of myself and co-workers. Since the approved protocol was written something like "... After volunteers receive the test product with 250 ml. of water, they do not allow to lay down. Only sit or semi-reclining is allowed for two hours after drug administration....." There are no problem for all of previous study until this. At first period, one of our volunteer blacked out at the early time point (40 minutes after drug administration) of blood drawing schedule [for your information, Tmax of this study drug (from literature) is around 1.5 - 4 hrs]. The volunteer was still conscious but lied down for 3 hrs and insisted to continue the study. The vital sign was OK. No problem with blood pressure and the doctor came to investigate him immediately and confirmed that he was OK to continue. This volunteer can complete both period with no harm. Here are the questions 1. Is this a major deviation in GCP point of view? 2. The study staffs knew that this is a protocol deviation. Are we make wrong decision to let this volunteer continued in second period? If the point concerned is not concern for GCP but for the drug concentration in plasma. 3. OK.... what was passed is passed. Now among our staffs are discussing about should we drop out this subject or not? The QA with Mr.Statistician said : "Of course, we should drop him because this is protocol deviation. Why should we keep him?" The clinical persons replied : "Hey!! both of you were not understand the clinical point of view. Just laying down is only minor deviation that may not effect absorption pattern. So it is OK to keep him." The QA : "If you think there are little effect on absorption, why you write it down in the protocol............." I think the dialogue above can clearly explain the situation. Please kindly give me some comment on this. Are our protocol to strict or it is OK? Is that true that just laying down is not a serious thing to be concern (just record it what happened and continue)? 4. If someone here had ever experienced this kind of this situation. Please share your story if you feel comfort. May this is quite a silly topic but your helps will make me understand more. Thanks in advance YT |
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kaushalesh ☆ 2009-09-24 12:35 (5707 d 10:53 ago) @ YT Posting: # 4242 Views: 7,604 |
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Dear YT ❝ 1. Is this a major deviation in GCP point of view? ❝ 2. The study staffs knew that this is a protocol deviation. Are we make ❝ wrong decision to let this volunteer continued in second period? Indeed! If your study staff knew that this is a protocol deviation then what is the point to continue with that particular subject. Any deviation in the protocol is a deviation and that is an abstract fact. so you shouldn't try to hide or modify the fact. ❝ The clinical persons replied : "Hey!! both of you were not understand the ❝ clinical point of view. Just laying down is only minor deviation that ❝ may not effect absorption pattern. So it is OK to keep him." Mostly with the ER/XR formulations this is a case that subject should stay upright for some time and movement should be restricted after administration of dosage because that can affect the gastric motility and gastric residence time of the dosage unit. ❝ The QA : "If you think there are little effect on absorption, why you ❝ write it down in the protocol............." The outlier criterion should be pre-defined in the protocol and has to be observed scrupulously. Regards Kaushalesh |
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Ohlbe ★★★ France, 2009-09-25 11:29 (5706 d 11:58 ago) @ kaushalesh Posting: # 4249 Views: 7,588 |
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Dear Kaushalesh and YT, ❝ Indeed! If your study staff knew that this is a protocol deviation then ❝ what is the point to continue with that particular subject. I wouldn't be as strict as you. Some protocol deviations are minor and do not justify the exclusion of the subject. Whenever a protocol deviation occurs the investigator has to decide whether is is major or minor, and whether the subject can continue or not. In this case the investigator decided to continue. You may disagree with the decision, but it was taken. ❝ Any deviation in the protocol is a deviation and that is an abstract fact. ❝ so you shouldn't try to hide or modify the fact. Nobody suggested to hide the fact. Deviations should indeed be reported in the sudy report. ❝ The QA : "If you think there are little effect on absorption, why you ❝ write it down in the protocol............." Because everybody uses standard protocols, with very little adaptation to the drug studied. Some criteria may be critical for one drug, but of little relevance for the next. YT, in the case of your drug, is there anything in the literature on the influence of posture ? This will help decide whether the protocol deviation is major or not. ❝ The QA with Mr.Statistician said : "Of course, we should drop him because ❝ this is protocol deviation. Why should we keep him?" Problem: we usually don't plan "per protocol" and ITT populations in BE protocols... Whatever you decide: take the decision before you analyse the samples from this subject. Regards Ohlbe — Regards Ohlbe |
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Helmut ★★★   Vienna, Austria, 2009-09-25 18:10 (5706 d 05:18 ago) @ Ohlbe Posting: # 4252 Views: 7,535 |
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Dear Ohlbe and all! I agree with all points Ohlbe made. I think Mr. Statistician is a little bit overreacting. The decision whether a protocol deviation is minor or major is not his business. Imaging a situation where 500 mg paracetamol are allowed per period in order to treat headaches and the investigor decided to give a second dose. Biostatistics are a supportive technique, decisions always have to be based on clinical grounds. ❝ Whatever you decide: take the decision before you analyse the samples from ❝ this subject. I guess by 'analyse' you mean the statistical analysis? I would always perform bioanalyses - even if the decision was against keeping the subject in the evaluation. What if regulators want to see an evaluation including the subject two years later - when biosamples went already to the garbage bin? — Dif-tor heh smusma 🖖🏼 Довге життя Україна! ![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png) Helmut Schütz ![[image]](https://static.bebac.at/img/CC by.png) The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
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Ohlbe ★★★ France, 2009-09-25 18:42 (5706 d 04:46 ago) @ Helmut Posting: # 4253 Views: 7,500 |
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Dear Helmut, ❝ What if regulators want to see an evaluation including the subject ❝ two years later - when biosamples went already to the garbage bin? You're making a point there. I didn't see it this way  Regards Ohlbe — Regards Ohlbe |
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YT ☆ Thailand, 2009-09-25 19:56 (5706 d 03:32 ago) @ Ohlbe Posting: # 4254 Views: 7,483 |
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Oh!!! all of your comments are very useful for me and our staffs. Myself and colleagues would like to give our big thanks for all of you. This can be one of a good case study for us. By the way, further suggestions are still welcome. Regards, YT (with happy face)  |
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boonchai_l ☆ Thailand, 2009-09-28 08:37 (5703 d 14:50 ago) @ Helmut Posting: # 4257 Views: 7,401 |
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Dear HS, ❝ I agree with all points Ohlbe made. I think Mr. Statistician is a little ❝ bit overreacting. The decision whether a protocol deviation is minor or ❝ major is not his business. Ummmm.., I don't know it is my business, or not? I just give my opinion to everyone in meeting whether please caution about bias. Previously, one person in the meeting answered QA's question about that subject "why don't we drop him out after bio analysis? when his plasma concentration is irregular from another period because that shows laying down effect to plasma concentration". I had realized already that I don't have right to judge which deviation is minor or major but in this case I have to give opinion. I don't concern what is protocol deviation because that is QA duty. I give opinion because I only don't want to let it go without discussion concerning bias. But my opinion support QA. Regards, Boonchai L. (Mr.Statistician) |
Ing. Helmut Schütz