Discontinuation trials

Nevertheless, some long-term efficacy trials have been conducted. These continuation studies are different from relapse-prevention or discontinuation trials in some very important ways. Instead of just looking at patients who have responded... 

Ratain, M., Preliminary antitumor activity of BAY 43-9006 in metastatic renal cell carcinoma and other advanced refractory solid tumors in a phase 11 randomized discontinuation trial (RDT), Proc. Am. Soc. Clin. Oncol., 22, 381, Abstr. 4501, 2004. 

In a prospective placebo-controlled discontinuation trial, we recently demonstrated the efficacy of nortriptyline in doses of up to 2 mg/kg daily in 35 school-aged youth with ADHD (Prince et al., 2000). In that study, 80% of youth responded by week 6 in the open phase. During the discontinuation phase, subjects randomized to placebo lost the anti-ADHD effect. There... 

Discontinuation trials, either controlled or open, usually are not likely to have any direct benefit and may well have real risks, such as relapse, suicide, and loss of employment. Such studies need additional scrutiny and safeguards to minimize risk and to strengthen consent procedures. There are some situations in which a discontinuation study may be considered. For example, to determine whether long-term treatment is needed, a study design might randomly assign patients who have responded successfully to a particular treatment to either a continuation or discontinuation of that treatment. Relapse rates across these two conditions could... 

The risk of relapse in discontinuation trials depends on many non-pharmacological, often poorly controllable factors, notably the expectations of the patients, doctors and nurses, other environmental factors, the duration of hospitalization and prior treatment, and the time interval since the last acute psychotic episode. On the basis of an analysis of 14 discontinuation trials, Kane and Lieberman (1987) found that the relapse rate varied greatly from study to study depending on the trial, relapse rates of 30 86% with clustering around 60 70% have been reported in the first 12 months after placebo substitution. According to Kane and Lieberman, this scatter is a result of the different inclusion criteria applied and the different definitions of relapse . 

Controlled discontinuation trials show that about half of all depressive patients suffer a serious relapse within 6 months if their antidepressant medication is withdrawn shortly after the disappearance of acute symptoms with continuation therapy, only about one-fifth of patients experience a relapse in the same period. The difficulty for the treating doctor is to estimate reliably how long he should continue to prescribe antidepressants for patients who have overcome depression. Consensus groups suggest that this period should be between four and six months after the symptoms of depression have resolved (Montgomery, 1997) even mild continuing symptoms may indicate that a depressive episode has not ceased completely and that the treatment should be continued further (Lader, 2001). 

The use in the quantum mechanical calculations of discontinuous trial functions constructed from exclusive orbitals has been discussed by Weave and Parr 148> and Hall 149>, who establish that, by using, e.g., the Green s function to turn Schrodinger s differential equation into an integral equation 14 ), one can do a priori quantum mechanical calculations on molecules using as basis functions atomic orbitals on different nuclei that are rigorously cut off so that no orbital on one atom has a non-vanishing overlap with any orbital on another atom 148>. 

Do not discontinue trials if ineffective at low doses (<50 mg) as many patients with difficult cases may respond to higher doses (f 50-300 mg, even up to 600 mg in some cases)... 

Ratain MJ, EisenT, Stadler WM, Elaherty KT, Kaye SB, Rosner GE, Gore M, Desai AA, Patnaik A, Xiong HQ, Rowinsky E, Abbruzzese JE, Xia C, Simantov R, Schwartz B, O Dwyer PJ. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006 Jun 1 24(16) 2505-12. 

Despite promising early data on activity, further development of SC-48334 (15)(iV-bu-tyl-deoxynojirimycin) for HIV infection was discontinued. Trials in AIDS/ARC patients indicated that the drug had no significant effect on p24 antigen levels or CD4 cell counts (42). SC-48334 (15) was not found to be of any ma-... 

Ratain MJ, Eisen T, Stadler WM et al. (2006) Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma J Clin Oncol 24 2505-2512... 

Resiquimod (R-848) Agonist Genital Herpes Phase II clinical trials discontinued... 

TLR-9 has also been used to target asthma with several compounds in preclinical trials such as second generation CpG-ODNs and HYB2093. 1018 ISS has also been tested in asthma. Defence against infectious disease is also enhanced through TLR-9. CpGIOlOl was in phase II trails as a Hepatitis C target but has been discontinued. 

Initial Situation A product contains three active components that up to a certain point in time were identified using TLC. Quantitation was done by means of extraction/photometry. Trials to circumvent the time-consuming extraction steps by quantitative TLC (diffuse reflection mode) had been started but were discontinued due to reproducibility problems. The following options were deemed worthy of consideration ... 

Economic studies should cover the full period over which the interventions could be expected to have an effect on resource use, survival and health-related quality of life. However, the economic evaluations of donepezil were based on effectiveness data from a limited number of trials, which were short in duration. This has a number of implications. First, the analysis can be limited to the effect of the drug during the period for which effectiveness data were available. In this case, it may be assumed that the treatment effect ceased after 6 months (Stewart et al, 1998). This assumption would only be valid if the donepezil were also discontinued at 6 months. If this is not the case, then the overall costs of the dmg may be underestimated and the benefits overestimated. 

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