Clinical trials safety issues

The preclinical trials are performed in in vitro and animal studies to assess the biological activity of the new compound. In phase 1 of the clinical trials the safety of a new drug is examined and the dosage is determined by administering the compound to about 20 to 100 healthy volunteers. The focus in phase II is directed onto the issues of safety, evaluation of efficacy, and investigation of side effects in 100 to 300 patient volimteers. More than 1000 patient volunteers are treated with the new drug in phase 111 to prove its efficacy and safety over long-term use. 

The first issue lies in the whole realm of the human disease process itself. Many adverse drug events mimic diseases and vice versa. Is an adverse event really an adverse event, or is it merely a natural occurrence of a disease process that is entirely independent of drug exposure The science of drug safety is often complicated by the lack of objective markers of drug toxicity that can systematically separate a disease process from an adverse drug event process [2]. Clinical trials, often viewed as the gold standard to assess efficacy, are simply too limited in scope to answer safety questions in a systematic way. 

A cancer patient may encounter many different health care professionals phlebotomists, pathologists, surgeons, medical and radiation oncologists, physician assistants, pharmacists, nurses, counselors, dieticians, social workers, and chaplains all may be involved with a single patient. Each one plays an important role in care of the cancer patient. The pharmacist s role may include education of patients and family members, education of staff about new agents and safety issues, preparation of therapies, resolution of reimbursement issues, development of order sets, and participation in clinical trials. Each patient should have access to an interdisciplinary team to assist him or her during treatment. 

TRPV1 is a nonselective cation channel predominantly expressed in sensory neurons and activated by capsaicin, heat (>42°C), pH (<5.4), and noxious stimuli. Several compounds have advanced into clinical development and have been extensively covered in recent reviews [5,34—39]. Among these, MK-2295 (structure not disclosed), AMG 517 (38), SB-705498 (39), and GRC-6211 (structure not disclosed) have reportedly encountered safety issues [35]. In phase II clinical trials with MK-2295, patients experienced an increase in core body temperature... 

Proper and comprehensive planning of a clinical trial is essential to the successful development of any drug. The first issue to be considered when developing a trial protocol is to define precisely what questions the trial results should be capable of answering. As discussed previously, the terms safety and efficacy are difficult to define in a therapeutic context. An acceptable meaning of these concepts, however, should be committed to paper prior to planning of the trial. 

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 ... 

DoD is not just another purchaser in a commercial market, however. It becomes a developer of drugs when demand is mainly or exclusively for military use. Under these circumstances, DoD requirements for CBW defense drugs involve the department in the full spectrum of research, development, testing for safety and effectiveness through clinical trials or alternate means, production, acquisition, and issues of medical use. (This may also be the case for naturally occurring diseases that rarely appear in the United States and for which the domestic civilian market is limited.)... 

Where you stand [on an issue] depends on where you sit is an old truism of public administration. It is essential, therefore, to clarify at the outset the perspective we bring to this examination of DoD-FDA interactions. The literature on commercial drug development emphasizes the complexity and uncertainty of research and development, especially clinical trials, and the FDA regulatory requirements for safety and effectiveness that a new drug must meet before... 

To identify a justified risk in a healthy population requires clinical trials and if the risk is very low inordinate numbers of patients are required to identify issues. These become extremely expensive in practice and this is one reason why vaccines are subject to postlicencing and postmarketing surveillance for safety. 

Even in the developed world market, size and the contrihution a medication is expected to make to the bottom line play the largest role in determining whether companies invest in R D on new molecules. In the mid- to late 1980s, 43 per cent of the terminations in the development of new compounds were for economic reasons versus 31 per cent for efficacy issues and 21 per cent for safety problems (DiMasi 1995). Companies do not hesitate to terminate ongoing clinical trials if their commercial priorities change, despite the fact that this means that there will be no meaningful results from these trials (Psaty and Rennie 2000). 

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