Control group in clinical trials

International Conference on Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH). Topic ElO Note for Guidance on Choice of Control Group in Clinical Trials, CPMPIICHI364I96. London European Agency for the Evaluation of Medicinal Products, 2001. 

ICH ElO Choice of control group in clinical trials Step 5 (2000)... 

ICH ElO (2001) Note for Guidance on Choke of Control Group in Clinical Trials ... 

The Office of Biostatistics has taken the lead in the development of several guidance documents on specific topics, including ICH E9, Statistical Principles in Clinical Trials, and ICH E10, Choice of Control Groups in Clinical Trials. It is advisable for sponsors to follow these guidances. 

Hsu, J. C. (1996). Multiple Comparisons Theory and Methods. Chapman Hall, London. Hsu, J. C., Chang, J. Y., and Wang, T. (2002). Simultaneous confidence intervals for differential gene expressions. Technical Report 592, The Ohio State University, Columbus. ICH E10 (1999). Choice of Control Groups in Clinical Trials. CPMP (Committee for Pro-pritary Medical Products), EMEA (The European Agency for the Evaluation of Medical Products), London, Draft ICH (International Conference on Harmonisation). Efficiency guidelines, http //www.ich.org. 

External validity can also be affected if trials have protocols that differ from usual clinical practice. For example, prior to randomization in the trials of endarterectomy for symptomatic carotid stenosis patients had to be diagnosed by a neurologist and to have conventional arterial angiography, neither of which are routine in many centers. The trial intervention itself may also differ from that used in current practice, such as in the formulation and bioavailability of a drug, or the type of anesthetic used for an operation. The same can be true of the treatment in the control group in a trial, which may use a particularly low dose of the comparator drug or fall short of best current practice in some... 

On May 19, 2004, docetaxel was approved for the treatment of metastatic prostate cancer. The approval was based on the TAX327 study, a randomized, multicenter global clinical trial enrolling over 1000 men with metastatic, hormone-refractory prostate cancer. The study compared docetaxel 75 mg/m every 3 weeks and prednisone 5 mg twice a day with docetaxel 35 mg/m weekly five out of six weeks and prednisone 5 mg twice a day and mitoxantrone 75 ng/m every 3 weeks and prednisone 5 mg twice a day. Docetaxel, in combination with prednisone, given every 3 weeks showed a survival advantage of approximately 2.5 months over the control group in the trial p =. 009). The most common adverse events reported were nausea, alopecia, and bone marrow suppression. In addition, fluid retention and peripheral neuropathy, known effects of docetaxel, were... 

E10 Choice of Control Group and Related Issues In Clinical Trials... 

Yamaguchi T, Sano K, Takakura K, Saito I, Shinohara Y, Asano T, Yasuhara H. Ebselen in acute ischemic stroke a placebo-controlled, double-blind clinical trial. Ebselen study group. Stroke 1998 29 12-17. 

Hudson, Christopher G., Socioeconomic Status and Mental Illness Tests of the Social Causation and Selection Hypotheses , American Journal of Orthopsychiatry 75, no. 1 (2005) 3-18 The Humble Humbug , The Lancet 2 (1954) 321 Hunter, Aimee M., Andrew F. Leuchter, Melinda L. Morgan and Ian A. Cook, Changes in Brain Function (Quantitative EEG Cordance) During Placebo Lead-in and Treatment Outcomes in Clinical Trials for Major Depression , American Journal of Psychiatry 163, no. 8 (2006) 1426-32 Hyland, Michael E., Do Person Variables Exist in Different Ways , American Psychologist 40 (1985) 1003-10 Hypericum Depression Trial Study Group, Effect of Hypericum Perforatum (St John s Wort) in Major Depressive Disorder A Randomized Controlled Trial , Journal of the American Medical Association 287 (2002) 1807-14... 

Phase IV. Studies or trials conducted after a medicine is marketed to provide additional details about the medicine s efficacy or safety profile. Different formulations, dosages, durations of treatment, medicine interactions, and other medicine comparisons may be evaluated. New age groups, races, and other types of patients can be studied. Detection and definition of previously unknown or inadequately quantified adverse reactions and related risk factors are an important aspect of many Phase IV studies. If a marketed medicine is to be evaluated for another (i.e., new) indication, then those clinical trials are considered Phase II clinical trials. The term postmarketing surveillance is frequently used to describe those clinical studies in Phase IV (i.e., the period following marketing) that are primarily observational or nonexperimental in nature, to distinguish them from well-controlled Phase IV clinical trials or marketing studies. 

For further discussion on control groups and placebo in clinical trials, see Temple and Ellenburg. ... 

S.5.5.2.3 Historical controls Since many clinical trials are conducted in the same diseases, with the same control treatments there is an obvious desire to make the most use of this potentially valuable information. Can we compare the results of a new treatment in a group of patients with a group of control patients extracted from a historical database For example, suppose we are testing a new treatment for migraine headache and 60% of patients improve in the first 2 h post-treatment, compared to 30% in a group of historical control patients treated who had been treated with the current gold standard. Are we able to conclude that the new treatment is preferable to the gold standard ... 

Oseltamivir may not be indicated for use in certain individuals. Its efficacy in patients with chronic cardiac or respiratory disease has not been established. In clinical trials, no difference in the incidence of complications was seen between treatment and control groups. The efficacy of oseltamivir has not been demonstrated in immunocompromised patients, patients who begin treatment after 40 hours of symptoms, or patients given repeated prophylactic courses of therapy. Dosage adjustment is recommended for individuals with renal insufficiency the drug s safety in patients with hepatic insufficiency is unknown. 

Increased rate of bacterial pneumonia was observed in subjects treated with enfuvirtide in clinical trials (4.68 pneumonia events per 100 patient-years in the treatment group versus 0.61 events per 100 patient-years in the control group)... 

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