Clinical Trials - Practical Issues in Labeling the Trial Drugs
The double blind controlled clinical trials are universally accepted as the gold standard for estimating the efficacy of a new treatment in comparison with a standard drug or placebo. Medical community and pharmaceutical industry have been practicing this since 1950. In double blind Randomized Controlled Clinical Trials, the patients are randomized to the treatments by using random number tables or computer generated random numbers. The random number list will be prepared by the biostatistician with subject ID and the drug names. This list will be sent to the sponsor for the preparation of drug for each individual patient. The sponsor must ensure that the drug packing is according to the industry standard and that must follow the international guidelines such as International Conference on Harmonization (ICH). He must also ensure that the test drug and the corresponding comparator (s) are similar in taste, smell, shape and color including out-side packaging. Also the number of capsules / tablets must be same. If the drug is in the form of syrup, the quantity must be equal in addition to the above requirements. The objective of this paper is to highlight issues in labeling the trial drugs, which needs to be taken care of by the sponsor / researcher while planning for a clinical trial.
Issue in Labeling the Trial Drug
Since randomized controlled clinical trial is an inevitable phenomenon in the pharmaceutical industry, every minute aspect of the trial related activities must be given due attention. One of such activities is drug labeling. It is observed that certain researchers / sponsors do the drug labeling practice like mark 'A' for test treatment and 'B' for placebo or standard drug. Another way of drug labeling is like '1' and '2'. What is the problem with this kind of drug labeling practice?
Usually the sponsor / Clinical Research Organization would provide the random allocation list to the investigator with codes as above along with subject ID. As per the double blind trial concept, the clinician / investigator or the patient does not know the identity of the drug 'A' or 'B'. Once a patient is eligible for the trial, the investigator will assign the drug 'A' or 'B' according to the random allocation list. Is there any draw back in this procedure? Apparently there is no problem, if the investigator is not very keen in knowing the result(s) of the drug(s). But some times he may observe the effectiveness of the two drugs by regularly watching the progress / improvement of the patient. Suppose there is a situation in which drug 'A' is active and drug 'B' is a placebo.
Then the clinician / investigator could make out the drug identity by seeing the progress of the patient's condition, probably after 5-10 patients undergone the treatment. This is because we know that there is no drug e effect for placebo and the active drug has some effect. This is more evident when we conduct the superiority clinical trials.
Yet another situation is in which one drug is giving more adverse events than the other drug. Then also the clinician / investigator could be able to identity of the drugs. Thus the investigator is in a position to guess at least which drug is active and which is inactive. This will defeat the purpose of double blind randomized controlled clinical trials. These issues may occur in triple blind clinical trials also.
Conclusion
According to ICH Guideline for Good Clinical Practice (E6), the sponsor should ensure that the trial products are manufactured in accordance with Good Manufacturing Practice and are coded and labeled in a manner that protects the blinding. Thus the researchers / sponsors are bound to follow the International guidelines while conducting the clinical trials.
Recommendations
The author recommends that there should not be any labeling or marking out side the trial drug container / box / bottle, in order to get the best results from a double blind randomized controlled clinical trials. The best solution for this is to entrust the job of drug allocation to a third party like Clinical Research Organization who would not directly involved in the day-to-day activities of the patient management. The Clinical Research Organization should not disclose the random allocation list to the investigator until the trial is over, except for situations like medical emergency when the occurrence of any serious adverse events.
Issue in Labeling the Trial Drug
Since randomized controlled clinical trial is an inevitable phenomenon in the pharmaceutical industry, every minute aspect of the trial related activities must be given due attention. One of such activities is drug labeling. It is observed that certain researchers / sponsors do the drug labeling practice like mark 'A' for test treatment and 'B' for placebo or standard drug. Another way of drug labeling is like '1' and '2'. What is the problem with this kind of drug labeling practice?
Usually the sponsor / Clinical Research Organization would provide the random allocation list to the investigator with codes as above along with subject ID. As per the double blind trial concept, the clinician / investigator or the patient does not know the identity of the drug 'A' or 'B'. Once a patient is eligible for the trial, the investigator will assign the drug 'A' or 'B' according to the random allocation list. Is there any draw back in this procedure? Apparently there is no problem, if the investigator is not very keen in knowing the result(s) of the drug(s). But some times he may observe the effectiveness of the two drugs by regularly watching the progress / improvement of the patient. Suppose there is a situation in which drug 'A' is active and drug 'B' is a placebo.
Then the clinician / investigator could make out the drug identity by seeing the progress of the patient's condition, probably after 5-10 patients undergone the treatment. This is because we know that there is no drug e effect for placebo and the active drug has some effect. This is more evident when we conduct the superiority clinical trials.
Yet another situation is in which one drug is giving more adverse events than the other drug. Then also the clinician / investigator could be able to identity of the drugs. Thus the investigator is in a position to guess at least which drug is active and which is inactive. This will defeat the purpose of double blind randomized controlled clinical trials. These issues may occur in triple blind clinical trials also.
Conclusion
According to ICH Guideline for Good Clinical Practice (E6), the sponsor should ensure that the trial products are manufactured in accordance with Good Manufacturing Practice and are coded and labeled in a manner that protects the blinding. Thus the researchers / sponsors are bound to follow the International guidelines while conducting the clinical trials.
Recommendations
The author recommends that there should not be any labeling or marking out side the trial drug container / box / bottle, in order to get the best results from a double blind randomized controlled clinical trials. The best solution for this is to entrust the job of drug allocation to a third party like Clinical Research Organization who would not directly involved in the day-to-day activities of the patient management. The Clinical Research Organization should not disclose the random allocation list to the investigator until the trial is over, except for situations like medical emergency when the occurrence of any serious adverse events.
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