Clinical trials overview

Figure 4.1 An overview of the life history of a successful drug. Patenting of the product is usually also undertaken, often during the initial stages of clinical trial work...

The physicochemical and other properties of any newly identified drug must be extensively characterized prior to its entry into clinical trials. As the vast bulk of biopharmaceuticals are proteins, a summary overview of the approach taken to initial characterization of these biomolecules is presented. A prerequisite to such characterization is initial purification of the protein. Purification to homogeneity usually requires a combination of three or more high-resolution chromatographic steps (Chapter 6). The purification protocol is designed carefully, as it usually forms the basis of subsequent pilot- and process-scale purification systems. The purified product is then subjected to a battery of tests that aim to characterize it fully. Moreover, once these characteristics have been defined, they form the basis of many of the QC identity tests routinely performed on the product during its subsequent commercial manufacture. As these identity tests are discussed in detail in Chapter 7, only an abbreviated overview is presented here, in the form of Figure 4.5. 

Edelstein, M.L., Abedi, M.R., Wixon, 1, and Edelstein, R.M. 2004. Gene therapy clinical trials worldwide 1989-2004 - an overview. Journal of Gene Medicine 6(6), 597-602. 

The intention of this book is to provide an overview of how a drug is discovered, the amount and types of laboratory tests that are performed, and the conduct of clinical trials before a drug is ready to be registered for human use. Of importance is the role of regulatory authorities in these processes. Through... 

Schneider LS, Olin JT. (1994). Overview of clinical trials of Hydergine in dementia. Arch Neurol. 51 787-97. 

Lickey ME, Gordon B. (1991). Medicine and Mental Illness. New York W. H. Freeman and Company. Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D. (1996). St. John s wort for depression—an overview and meta-analysis of randomised clinical trials. BMJ. 313(7052) 253-58. Lingjaerde 0, Foreland AR, Magnusson A. (1999). Can winter depression be prevented by Ginkgo biloba extract A placebo-controlled trial. Acta Psychlatr Scand. 100(1) 62-66. 

Volz HP. (1997). Controlled clinical trials of hypericum extracts in depressed patients—an overview. Pharmacopsychiatry. 30(suppl 2) 72-6. 

Strawn LM, Shawver LK. Tyrosine kinases in disease Overview of kinase inhibitors as therapeutic agents and current drugs in clinical trials. Exp Opin Invest Drugs 1998 7 553-573. 

Proper and comprehensive planning of a clinical trial is essential to the successful development of any drug. Clinical trial design is a subject whose scope is too broad to be undertaken in this text, and only a brief overview of the subject is presented below. The interested reader is referred to the Further Reading section at the end of this chapter. The general principles presented below are relevant to phase II, and particularly phase III, clinical trials. As the bulk of the estimated 300-500 million required to develop a drug is spent on clinical trials, a poorly planned and/or executed clinical trial can be very costly to the drug developer. 

Linde, K., Ramirez, G., Mulrow, C.D., Pauls, A., Weidenhammer, W, and Melchart, D. (1996) St. John s wort for depression an overview and meta-analysis of randomised clinical trials. BMJ 313 253-258. 

Volz HP. Controlled clinical trials of Hypericum extracts in depressed patients an overview. Pharmacopsychiatry 1997 30 72-76. 

Linde K, Ramirez G, Mulrow CD, et al. St John s wort for depression — an overview and meta-analysis of randomized clinical trials. BMJ 1996 313 258-261. 

In addition, the Office of Scientific Investigations (CDER) conducts biomedical audits of clinical investigator s sites. These investigations focus primarily on sites involved in pivotal clinical trials, but may also involve other sites. Investigators should be informed that they should contact the applicant when the FDA notifies them of an upcoming inspection. The spon-sor/applicant is generally not permitted to be involved in an FDA inspection of an investigator s site. Refer to Chap. 3 for an extensive overview of the FDA s expectations of clinical trial activities. 

Lasala JM, Stone GW, Dawkins KD, et al. An overview of the TAXUS EXPRESS paclitaxel-eluting stent clinical trial program. J Interv Cardiol 2006 19 422-43 I. 

Edelstein ML, Abedi MR, Wixon J, Edelstein RM. Gene therapy clinical trials worldwide 1989-2002—an overview, J Genet Med 2004 6 597-602. 

The book is comprised of five sections with part I covering systemic and endoluminal therapy with an incisive overview of hemostasis and thrombosis part II covers local therapy with several chapters devoted to drug-eluting stents and restenosis therapies part III covers cell therapy and therapeutic angiogenesis and includes chapters on cell transplantation and clinical trials in cellular therapy part IV covers adjunctive pharmacotherapy with chapters devoted to various patient populations including those with heart failure, diabetes, atrial fibrillation, peripheral artery disease,... 

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