Clinical trials with historical controls

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 ... 

In clinical trials the cumulative risk of death 35 days after starting treatment was 9% in the lepirudin-treated patients, compared with 18% in historical controls cumulative risk of new thromboembolic complications was 6% with lepirudin and 22% in historical controls... 

E. Therapeutic response Thrombin-dependent tests show dose dependency [aPTT rise proportionally to dose of Refludan]. The key criteria of efficacy in two pivotal clinical trials from a laboratory standpoint were platelet recovery and effective anticoagulation. Seven days after the start of treatment with Refludan in patients with HIT, the cumulative risk of death, limb amputation, or new thromboembolic complication was substantially lower than in a historical control group. 

The key parameter for any drug product is its efficacy as demonstrated in controlled clinical trials. The time and expense associated with such trials make them unsuitable as routine quality control methods. Therefore, in vitro surrogate tests are often used to assure that product quality and performance are maintained over time and in the presence of change. A variety of physical and chemical tests commonly performed on semisolid products and their components (e.g., solubility, particle size and crystalline form of the active component, viscosity, and homogeneity of the product) have historically provided reasonable evidence of consistent performance. More recently, in vitro release testing has shown promise as a means to comprehensively assure consistent delivery of the active component(s) from semisolid products. 

Historically, steroids and ACTH have been used in the treatment of MS relapses. While both suppress cell mediated and humoral immune responses, the major effect in MS acute relapse is to suppress inflammation. A meta-analysis of randomized controlled clinical trials (Brusaferri and Candelise, 2000) indicates that any type of steroid or ACTH treatment significantly accelerates short-term recovery from an acute MS relapse. However, there is no evidence that steroids reduce the risk of an MS relapse. A randomized trial of oral versus intravenous (IV) methyl prednisolone for treatment of acute relapses of MS shows no clear advantage of either treatment route (Barnes et al., 1997). Currently methyl precbisolone is considered standard of care for acute MS relapses. Methyl precbisolone (Solu-Medrol) is used with IV treatment for 3-5 days at 500-1000 mg/day. Methyl prednisolone IV therapy may be followed by a oral prednisone taper. The use of low dose oral precbisolone is also effective in conjunction with INFp therapies when flu-like side effects persist. 

Although randomized, controlled trials form the basis for some of the most reliable assessments of drug safety, pregnant women usually are not eligible for participation in clinical trials. Other types of data often are used to estimate the risk associated with medication use during pregnancy, such as animal studies, case reports, case-control studies, prospective cohort studies, historical cohort studies, and voluntary reporting systems. 

B. J. Kaplan, et al., Effective Mood Stabilization with a Chelated Mineral Supplement An Open-Label Trial in Bipolar Disorder. Journal of Clinical Psychiatry 62 (2001) 936-944 A. B. Mayer, Historical Changes in the Mineral Content of Fruits and Vegetables. British Food Journal. 99 (1997) 207-211 C. W. Popper, Do Vitamins or Minerals (Apart from Lithium) Have Mood-Stabilizing Effects Journal of Clinical Psychiatry 62, no. 12 (2001) 933-944 S. J. Schoenthaler and I. D. Bier, The Effect of Vitamin-Mineral Supplementation on Juvenile Delinquency Among American Schoolchildren A Randomized, Double-Blind Placebo-Controlled Trial. Journal of Alternative and Complementary Medicine 6 (February 2000) 7-17. 

Legend Hcoh Historical cohort study Pcoh Prospective cohort study RCT Randomized controlled trial Average mobility was calculated from the reported data [25] Overall clinical success was defined as patients having >25% improvement in ODI score at 24 months compared with the preoperative score, no device failure, no major complications, and no neurological deterioration [26], Five-year followup of this series have been reported in conference presentations [15], but these results have not yet appeared in the peer-reviewed literature. 

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