[discussion] technical confusion of clinical trial review

Source: medical economic news 2015-12-25 2015 is an unusual year Since the promulgation of No 117 document on July 22, the self-examination and verification of clinical trials has become the focus of the whole industry Up to now, in the past half a year, almost every 1-2 weeks, new announcements will be released The dynamic update of the enterprise's initiative withdrawal and the verification results of the drug regulatory department will always affect the attention of drug companies, contract research organizations (cros) and clinical trial institutions The announcement of the State Food and Drug Administration on the disapproval of 11 drug registration applications of 8 enterprises (No 229, 2015) released on November 11 even brought the attention of the whole industry to a new climax At the beginning of the self inspection, most people held a wait-and-see attitude How about the implementation? Is it as thunderous and rainy as the previous inspections? And the following teleconferences, announcements, and inspection results are constantly published Severe punishment and publicity for the problematic projects and responsible parties show that CFDA It is determined to thoroughly investigate all clinical data, and thoroughly solve the problem of falsification and non-standard test data First of all, this verification operation inspected phase I project rapidly and carefully, and gave a detailed inspection report This kind of determination and strength let the onlookers cheer up, and put high expectations on the next actions I hope that this time we can completely solve the problem that the clinical trial data that has existed for a long time is not true and accurate, set up a new industry benchmark, and sweep the industry of fraud, so as to bring a new atmosphere to the development of the whole industry The notice of the food and Drug Administration on Further Strengthening the self inspection and verification of drug clinical trial data (No 266, 2015) issued on December 17 aroused strong concern It is mentioned that "non-standard and incomplete problems that are really technical level and general defects shall only be handled as non approved problems." Does this mean that, even if it is not fraud, it will be regarded as "unreliable data" due to systematic defects in technical level, and thus "not approved"? According to document No 228 issued on November 10, the problems mentioned in the document include ECG traceability, outpatient follow-up subjects in hospital information system (his) These records are not fake clinical trials or incomplete data, but the current system fails to meet these requirements or does not match the current trial process The important details that need to be considered throughout the self-examination work since its inception, after several rounds of withdrawal As of December 14, there were only 668 projects left in 1622 projects, and more than half of them have been withdrawn in succession: first, the enterprises withdraw by themselves, and then the hospitals urge the enterprises to withdraw after inspection If the inspection standard for phase II and phase III clinical trials in this verification is that individual data cannot be traced due to technical reasons, that is to say, the data is not reliable, then it is estimated that 1622 projects will be spared, and even other projects will not be able to carry out the test So, what are the details of this verification work that need to be considered? 1 The test standard is unclear, is the current standard to be re established? Among the problems exposed in this inspection, fraud, fictitious data, tampering with data, etc., these behaviors should undoubtedly be dealt with severely to ensure the authenticity and reliability of clinical test data However, some data are incomplete, or due to the limitation of current technology, they are considered unreliable, which makes the practitioners confused and confused about how to do the project in the future For example, the current technical level is not up to the traceability of pregnancy test or bedside ECG 2 How to ensure the scientificalness and feasibility of the experiment at the same time of high standards and strict requirements? It is unfair for the enterprises that do the project seriously that some irresponsible personnel try to muddle through with some untrue and incomplete data Through this self-examination, the false data and projects with quality problems will be eliminated, and the whole industry will be refreshed, which will promote the industry to develop in the right direction At the same time of high standards and strict requirements, we should ensure the scientificity and feasibility For deliberately falsifying and fabricating data, it is responsible for the drug safety of the masses of the people; for non subjective intention falsifying, but the data is incomplete and nonstandard so that it can not prove the effectiveness and safety of drugs, it is also necessary to disapprove; However, for non subjective falsification, incomplete and non-standard data, but the available data can prove the effectiveness and safety of drugs, can we open up a net? From a scientific point of view, even if there are certain defects in the data, it can still prove the effectiveness and safety of drugs, which is a precedent A recent example is the FDA's finding that there are some data problems in the trial of apixaban that can not be used Although some of the data have been discarded, the remaining data can still be used to judge the effectiveness and safety of the drug, and the drug is still approved for marketing For FDA and EMA, as long as the key data can guarantee the authenticity and integrity, it meets the requirements 3 Impact on clinical trial institutions This examination also exposed many problems of clinical trial institutions More and more institutions choose to connect or suspend the test as little as possible in order to protect themselves At present, there are not many national certified clinical trial institutions, which are in short supply In order to cooperate with the organization, the sponsor often caters to some unreasonable requirements, which is also a cause of data problems After this self-examination, there are fewer institutions willing to take over the project, and the institutions are more cautious in choosing the project Will the sponsor accommodate the institutions more in order to find institutions to take over the project The scope, procedures and work requirements of the priority review are introduced in Document No 1, which shows the determination of the drug supervision department to speed up the review and actively listen to the opinions of all parties On December 18, at the second symposium of clinical trial committee of Chinese Pharmacology Society, CFDA's report proposed to strictly distinguish several situations and treat subjective falsification and objective data differently The industry is looking forward to the actual treatment of the drug regulatory department according to the specific situation, to grasp the appropriate scale A healthy, transparent and positive industry atmosphere is what practitioners hope to see It is a great honor for the industry to reverse the current non-standard situation and eliminate the following problems in the current test through the self inspection and verification work of the drug regulatory bureau 1 Some clinical trial institutions and researchers do not pay enough attention to the trial, rely on cro and manufacturers to complete the trial, and fail to fully fulfill their responsibilities as institutions and researchers Sometimes, there will even be a situation where researchers have been working as Pi of a project for a long time, but do not know the progress of the project It is believed that this situation will improve after this inspection 2 With the continuous inspection and publicity of CFDA, the industry will gradually strengthen self-discipline for individual cros in the industry to cater to the situation of the sponsor, laissez faire researchers and lack of management 3 In the past, some sponsors thought that they could wait for the product to go on the market after outsourcing the project to cro In the future, the responsibilities of the sponsor are very clear It is not in line with the requirements of GCP that the sponsor does not participate in the management of the whole project and wants to transfer all its responsibilities to cro Some of the sponsors tried to reduce the cost of research and development, and wanted to complete the product registration and listing with the minimum cost and time, which is not responsible for the drug safety of the masses, and to some extent, promoted the trend of clinical trial data fraud Conclusion < < I hope that this self inspection and verification work can set up a new atmosphere of serious test for the industry as expected We will give commendation to the enterprises that are rigorous in doing projects, and deal with the enterprises that are fraudulent strictly We will really set up the industry benchmark, create a real, transparent, rigorous and scientific industry atmosphere, and promote the healthy development of the whole industry.