Clinical trials request

Figure 8.12 Number of clinical trials requested per new drug application ...

Notification 698 of May 1980 does not provide much more information regarding clinical trials, requesting to submit at least 150 cases in at least five institutions for a new ethical drug application for approval. 

Judge whether the clinical trial request is appropriate... 

In addition to the expedited reporting described above, sponsors shall submit, once a year throughout the clinical trial, or on request, a safety report to the Competent Authority and the Ethics Committee. This should cover SUSARs, other serious adverse reactions, and an analysis of the subjects safety during the course of the trial. 

Requests for permission to conduct clinical trials with pharmaceuticals in the US are termed Investigational New Drug Applications (INDs). The applications are actually a request for an exemption to supply a drug without a marketing authorisation. A cover sheet (Form 1571) must accompany the application. This cover sheet should also be used with each subsequent communication with the FDA, with each form consecutively numbered, starting at 000 for the initial submission. A copy of the form is shovm in Figure 5.6. 

The conduct of clinical trials is regulated in all the countries, except Cypms. In Cypms, the policy of the Ministry of Health is not to permit clinical trials for experimental medical products. Multicountry clinical trials for products licensed in developed countries are undertaken in some institutions and regulated by ethics committees (Table 8.5). In these countries, approval of clinical trials is carried out either by the DRA, as in Estonia, Malaysia, Tunisia, Venezuela and Zimbabwe, or by ethics committees. When the DRA itself is responsible for control, information about the trials is processed centrally. In Tunisia, clinical trials form part of the registration process. Trials are requested, when deemed necessary, by the specialized committee charged with reviewing the new dmg. The trial proposal is then evaluated by the technical committee, and forwarded to the Health Minister for final approval. Cuba has a National Centre for the Coordination of... 

Bar charts can represent data similar to the data represented by a line plot, but in a visually different way. Sometimes bar charts are requested in clinical trial reporting instead of a line plot. The following example shows the data from the previous line plot represented as a bar chart. 

Moore s idea of analysing the data that had been sent to the FDA seemed brilliant, and I proposed that we work on it together. So we began. Moore wrote to the FDA invoking the Freedom of Information Act and requested the medical and statistical reviews of every placebo-controlled clinical trial for the treatment of depression by what, at that time, were the six most widely used new-generation antidepressant drugs Prozac, Seroxat (Paxil in... 

Stable expression of the recombinant protein is another pre-requisite. For production in CHO cell culture, narrow specifications of expression level are requested by the FDA. Consequently, plant-derived proteins need to be produced according to a defined scheme and within defined specifications in order to generate material suitable for clinical trials. Therefore, the expression level must be maintained within a defined range. For example, Prodigene Inc. assessed whether the E. coli Lt-B protein was uniformly distributed throughout the defatted maize germ by analyzing samples... 

The FDAMA bill essentially codified and expanded several regulatory actions initiated by the FDA during the 1990s. Among the incentives offered by the bill, companies will be offered an additional six months of patent protection for performing pediatric studies (clinical trials) on already approved products. In fact, the FDA was mandated by FDAMA to develop a list of over 500 drugs for which additional information would produce benefits for pediatric patients. The FDA is supposed to provide a written request for pediatric studies to the manufacturers (Hart, 1999). 

F-D-C Reports, Inc. (2000). FDA May Request Intermediate Enforcement Authority for Clinical Trials. The Pink Sheet, 62 (19) 16-17. 

Phase I, II, and III Trials An IND is submitted for each phase of clinical trial. Phases I to III. At any stage of the trial, the FDA has the authority to put clinical hold on the trial until deficiencies or safety issues are resolved. The Sponsor can request meetings with the FDA at various stages ... 

The clinical trial monitor is a temporary member of the site team. A good monitor will conduct scheduled visits, and the investigator and the site staff should provide sufficient time to answer questions and correct data in the CRF that has been transferred incorrectly from source documents. Common errors are omitting negative answers and signatures. The monitor will need space to work and should be provided with requested documentation, including medical records, for review. 

Laboratory safety data When the CRFs arrive at the data manager s office, questions will arise relating to laboratory safety data. Queries may occur at the investigator site and advice can be requested from the pharmaceutical physician associated with the clinical trial in the sponsor company. 

Supply on a particular patient basis encompasses various categories of unauthorised use of medicinal products. A product maybe imauthor-ised because it has been specially formulated for use it may be at the clinical trial stage of development, but be requested by doctors for use outside a trial it may have been authorised previously and then withdrawn from the market for commercial reasons, or because of safety, efficacy or quality concerns or it may be authorised currently, but for a different indication or patient population, or in a different country. 

Clinical trials are sometimes continued for an open extension period. This is permissible, provided there are genuine scientific reasons for continuing the study (rather than commercial reasons, such as attempting to create demand for the product) and that the appropriate regulatory clearance has been obtained. If the company does not wish to do this, it would be open to the doctor to request further supplies of the product, but the company must not invite him to do this. Any further supply to the doctor would then need to comply with the provisions regarding particular patient supply, unless the doctor has decided to carry out his own clinical trial. 

The Parties agree to adhere to the principles of medical confidentiality in relation to Clinical Trial Subjects involved in the Clinical Trial. Personal data shall not be disclosed to the Sponsor by the NHS Trust save where this is required directly or indirectly to satisfy the requirements of the Protocol or for the purpose of monitoring or adverse event reporting. The Sponsor shall not disclose the identity of Clinical Trial Subjects to third parties without prior written consent of the Clinical Trial Subject, in accordance with the requirements of the Data Protection Act 1998 and the principles set out in the Report of the Caldicott Committee on the review of patient identifiable information dated December 1997, a copy of which the NHS Trust shall supply to the Sponsor on request. 

The Ethics Committee shall give its opinion, before a clinical trial commences, on any issue requested. 

Before commencing any clinical trial, the sponsor shall be required to submit a valid request for authorisation to the competent authority of the Member State in which the sponsor plans to conduct the clinical trial. 

At the substantiated request of any Member State, the Agency or the Commission, the competent authority to which the request for authorisation was submitted shall supply aU further information concerning the clinical trial in question other than the data already in the European database. 

Where a Member State has objective grounds for considering that the conditions in the request for authorisation referred to in Article 9(2) are no longer met or has information raising doubts about the safety or scientific validity of the clinical) trial, it may suspend or prohibit the clinical trial and shall notify the sponsor thereof. 

The sponsor shall keep detailed records of all adverse events which are reported to him by the investigator or investigators. These records shall be submitted to the Member States in whose territory the clinical trial is being conducted, if they so request. 

Since the bottleneck on the clinical trial for taxol was in the supply, the NCI turned in 1989 to industrial partners, and issued a request for a Cooperative Research and Development Agreement, and selected Bristol-Myers Squibb (BMS) in 1991 as the partner in taxol development. BMS would take responsibility for the short-term supply of taxol, and NCI would sponsor research to deal with long-term supply. BMS collected 750,000 lbs of dried T. brevifolia bark from 38,000 trees during the 1991 growing season, sufficient to yield 25 kg of pure taxol to treat about 12,000 cancer patients. Hauser Chemical Research of Boulder, Colorado, was overseeing collection of yew bark and processing of the bark to extract taxol. BMS prepared the final dosage formulation and delivered it to the NCI for use in clinical studies. 

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