Clinical trials history

The development of nucleic acid-based therapeutics is not as straightforward as researchers had initially anticipated. Stability, toxicity, specificity, and delivery of the compounds continue to be challenging issues that need further optimization. In recent years, researchers have come up with intricate solutions that have greatly improved the efficacy of potential antisense, ribozyme, as well as RNAi-based therapeutics. Clinical trials for all these types of nucleic acid-based therapeutics are underway. So far, data from several trials and studies in animal models look promising, in particular, the therapies that trigger the RNAi pathway. However, history has shown that compounds that do well in phase I or phase II clinical trials may still fail in phase III. A striking example is the nonspecific suppression of angiogenesis by siRNA via toII-Iike receptor 3 (Kleinman et al. 2008). It will become clear in the near future which compounds will make it as a new class of antiviral therapeutics. 

The exact role of rituximab in RA is not clearly defined, but it is indicated for patients with moderate to severe RA with a history of inadequate response to DMARDs and other BRMs. Rituximab carries a black-box warning of fatal infusion reactions and severe mucocutaneous reactions even though these events did not occur during the RA clinical trials. The benefits of rituximab must be tempered against the safety concerns reported with use of rituximab in the oncology setting. 

The greatest advantage of psychotherapy over medication is that it reduces the likelihood of relapse after having got better. In 2005 a group of Dutch researchers conducted a clinical trial in which they examined the effect of adding cognitive therapy to treatment as usual in a group of patients with a history of... 

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...

One clinical trial showed that the combination of an ACE inhibitor and thiazide diuretic reduces the incidence of recurrent stroke in patients with a history of ischemic stroke or transient ischemic attacks. 

Additionally it has been observed that raloxifene reduces the risk of breast cancer by 58-66%, without producing an increased risk of endometrial cancer in postmenopausal women (Cummings et al. 1999 Jordan et al. 1998). The Multiple Outcomes of Raloxifene Evaluation (MORE) clinical trial is particularly eloquent in this regard (Cummings et al. 1999). A total of7704 postmenopausal women (average age 66.5 years) with osteoporosis and without history of breast or endometrial cancer were included. The trial, which was randomized and double-blind, used two doses of raloxifene (60 or 120mg/d) or placebo to as-... 

The structural modification of natural products is useful in several ways. The known pharmacology of bisindole alkaloids is enriched by the diversity of chemical structures that are made available by structure modification and total synthesis. These molecules have served as biochemical probes in several areas of biology, especially in those of microtubule assembly and drug resistance. The most elusive prize, however, has remained the discovery of new compounds with clinical activity. In recent years several compounds have been evaluated in clinical trials, but vinblastine and vincristine remain the only bisindole alkaloids approved for the treatment of cancer in the United States. These compounds are joined by vindesine in Europe, and at least two new derivatives are the subject of ongoing clinical trials. Considering the breadth of chemical research in this area, the overall yield as measured by new compounds with clinical activity has been relatively low, but this observation is not unique in history of analog development in cancer research. Nevertheless, the search continues, and this chapter details the chemical endeavors to discover a new bisindole alkaloid with clinical activity. 

There are obvious benefits to any future consulting physician to know something of the medical history of a study subject, including any significant data obtained from a past clinical trial that might affect future medical care. 

Many investigator sites employ part- or fulltime nurses to support the clinical trials. Nurses should never be considered to be an extravagance, because without them, the onus of administration and QC is solely on the investigator. The clinical trial nurse can help the investigator in many ways, but two of the most important are ensuring that the CRT reflects what is present in the source documents, such as essential events of the medical history of the subject, and close liaison with the sponsor s monitor. 

It is agreed in Japan that the key person for the successful conduct of clinical trials is the clinical research coordinator (CRC), equivalent to the study nurse or study coordinator. Despite lack of history of such a role and rather rigid labour environment in Japan, the concept of CRC is now well established and introduction of the CRC to hospitals is gradually progressing. 

The type of submission considered by DSEB to be appropriate for a PI update depends on the regulatory and clinical history of the drug in Australia and overseas, with special reference to the United Kingdom, United States, Sweden, Canada and the Netherlands. Submissions based on company sponsored clinical trials are usually required for drugs marketed for less than 5 years, whereas any of the three types of submission can be used for drugs marketed for more than 10 years. Drugs marketed between 5 and 10 years will be considered on a case by case basis, but it is generally expected that either a conventional or hybrid submission will be submitted. 

AppetiteAA/eight changes Anorexia was reported for venlafaxine-treated patients. A dose-dependent weight loss often was noted in patients treated for several weeks. Manla/Hypomania During clinical trials, hypomania or mania occurred in 0.5% of patients treated with venlafaxine. As with all antidepressants, use venlafaxine cautiously in patients with a history of mania. 

Seizures - In placebo-controlled clinical trials in patients with MDD, seizures occurred in 0.1% of patients treated with duloxetine and 0% of patients treated with placebo. Prescribe duloxetine with care in patients with a history of a seizure disorder. 

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