Clinical research development process

The clinical drug development process required by the US FDA, arguably the most stringent in the world, starts with the investigational new drug (IND) application prior to human testing. It reveals information about all known compounds to be used and includes the description of the clinical research plan for the product as well as the protocol for phase I studies. Preclinical study results also need to be revealed. 

The partition coefficient and aqueous solubility are properties important for the study of the adsorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) of drugs. The prediction of the ADME-Tox properties of drug candidates has recently attracted much interest because these properties account for the failure of about 60 % of all drug candidates in the clinical phases. The prediction of these properties in an early phase of the drug development process could therefore lead to significant savings in research and development costs. 

While most of the technologies described so far have been applied to academic research and the drug discovery processes, some of the applications described in the previous sections can equally well apply to the medical research community. Here the focus will be on some examples of the applications that are more exclusively relevant to this community, and will include aspects relevant to clinical research, both inside and outside the pharmaceutical development process. 

Focus of the development process for a new pharmaceutical is an essential aspect of success, but is also difficult to maintain. Clinical research units generally desire to pursue as many or as broad claims as possible for a new agent, and frequently also apply pressure for the development of multiple forms for administration by different routes. These forces must be resisted because they vastly increase the work involved in safety assessment, and they may also produce results (in one route) that cloud evaluation [and impede Institutional Review Board (IRB) and regulatory approval] of the route of main interest. 

Clearly, a balanced program that gives careful consideration to the limitations of using CROs — to run the studies, provide the statistical analyses, monitor the processes, and even, coordinate the studies performed outside the United States — needs to be evaluated against the more traditional approaches to drug development. The CRO in clinical research is discussed in detail in Chapter 21. 

Patent protection under general law usually lasts for up to around 20 years. This creates a difficulty in relation to medicinal products, as it can take some 12 years for the products to undergo research, development, the extensive clinical trials that are required in order to obtain a marketing authorisation and the authorisation process itself. These steps are also extremely expensive. The amount of time that remains during which the patent holder can exploit his patent and recoup his massive investment can be severely curtailed in relation to medicinal products. For this reason, the European Community has provided a form of additional patent-related protection for medicinal products authorised within the European Community, by means of a Supplementary Protection Certificate. A patent holder may apply for a certificate that takes effect at the end of the term of the basic patent, for a period equal to the period that elapsed between the date on which the application for the basic patent was lodged and the date of the first authorisation to place a product derived from the patent on the market in the Community, reduced by a period of 5 years. The maximum duration of the certificate is 5 years. The certificate applies to all medicinal products derived from the basic patent, but the additional time that can be obtained under the SPC is calculated in relation to the first product derived from the patent, authorised in the EU. 

There are two distinct phases in the process that eventually results in the availability of a new domestic product, and the proper measure of cost from a societal perspective depends on the phase in which one is in. To be successfully offered, a product must first go through several phases of research, development, and clinical testing culminating in regulatory approval. Once regulatory approval is achieved, firms then incur additional costs to market, produce, distribute, and transport the product. 

The use of intermediate endpoints to demonstrate clinical efficacy is common in clinical trials, because it reduces both the cost of the clinical development process and the time needed to demonstrate the efficacy of the therapy. Intermediate endpoints are most appropriate in clinical research if they have been shown to be related to the clinical outcome of interest, as in the following ... 

The argument against any given cell lineage can be made for hepatocytes and/or human cancer cell lines, both of which are a major part of the drug development process. There is also an emphasis on the pharmacodynamic mechanisms of the drug effect, because of the absence of CYP/transport members. Because a drug s pharmacokinetics are usually adequately characterized as part of the preclinical and early clinical development, pharmacodynamics remains an area of needed research. Specific steps have been taken to try to understand how relevant the CEPH cell lines are to other cancer cell line systems. 

In sales for instance several distributors may be appointed for different countries and centrally supplied with products. In development, companies may band together to share the tasks of process development, formulation and clinical research. Discovery research is clearly an area where cooperation and... 

As mentioned earlier, the expectation of the FDA is not only that the applicable regulations from 21CFRwill be complied with during the course of clinical trials, but also that pharmaceutical companies will develop adequate written policies and procedures to describe how the conduct their clinical research processes in compliance with the regulations. Table 2 provides a list of some procedures that Parts 50,56, and 312 require in writing. 

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