Perhaps we need to combine the June and August PR and see what contract changes need to be addressed per the August trial ammendement announcement. I have no doubt that they've been taking patients this entire time, where they were already enrolling patients, but just need to renogotiate the terms. I think it just caused a snafu in the contract negotiation part with the number of trial sites that may have not been further along. From below, looks like a repeat of step 2, step 3, and the last German step. I think it's safe to say the others are fine.
In the US, the steps required to initiate a site include the following. •The first step is the “site qualification,” in which both paperwork and onsite evaluations are done (of personnel, facilities, past clinical trial experience of both the institution and the personnel, etc.) to determine the capabilities of the medical center to serve as a site in the clinical trial. This step can take a month to arrange and complete.
•The second step is the review and approval of the clinical trial and all related documents (specific patient consent forms, data collection, etc.) by that medical center’s “Institutional Review Board (IRB).” In many medical centers, the IRB only meets once per month. The clinical trial package must be submitted weeks in advance, and the IRB review, questions, further submissions, further IRB review and decision typically take 2-3 months.
•The third step is the negotiation of a business contract (“Clinical Trial Agreement”) with the medical center’s legal department and clinical trial budget with the medical center’s budget department. The contract terms and budgets can vary substantially among medical centers within the same clinical trial. This process typically takes about 2 months.
•The fourth step is the “Site Initiation.” This involves arranging and conducting a full-day, detailed, joint training of all of the personnel who will be involved in the trial: e.g., the neurosurgeons, neuro-oncologists, head of the hospital’s pharmacy, pathologists, radiologists, nurses and others. The lead time for arranging this joint training with so many players on the same day is typically substantial. The training includes all aspects of the trial, including the patient eligibility criteria and procedures, treatment procedures, testing and monitoring procedures, data collection, etc.
Each of the above steps must be successfully completed before the next step at a site can be undertaken (because the sites will not proceed otherwise), and all of the steps must be successfully completed before a clinical trial can open for enrollment at that site. This lengthy process must be accomplished at each site individually for every site that participates in a clinical trial.
In Germany, for the DCVax-L clinical trial, significant additional steps must be completed in addition to the steps for US sites described above. •Each clinical trial site must obtain a regulatory license for tumor tissue collection and use from the local regulatory authorities in the jurisdiction where the trial site (i.e., medical center) is located. The requirements of the local regulators for these licenses vary. The preparation of the appropriate application package for the local regulators, and the review, decision and issuance of the tumor collection licenses by those regulators, takes a couple of months.
•Similarly, each clinical trial site must obtain a regulatory license for the leukapheresis blood draw (to collect the immune cells) from the local regulatory authorities in the jurisdiction where the trial site is located. The local regulators with the authority over leukapheresis licenses can be different than the local regulators with authority over licenses for tumor tissue collection. The preparation of the appropriate application package for the local regulators, and the review, decision and issuance of the leukapheresis collection licenses by those regulators, takes a couple of months. Fortunately, unlike the other steps involved in clinical trial site initiation, the tumor collection license and leukapheresis license can proceed in parallel, so that these two licenses can potentially be completed simultaneously within a couple of months.
•At many clinical trial sites in Germany, multiple separate business contracts must be negotiated. Separate contracts must be negotiated with the radiology department and with the leukapheresis department, in addition to the Clinical Trial Agreement described above. The requirements and terms for these additional contracts vary from site to site, and must be negotiated individually.
