Comparator trials

Torpex, Sensitivity to S.A. Fire. Results of Comparative Trials with Various Types of Explosives Attacked by 20mm Projectiles , BritOrdnBoardProc 31986 (August 1945) 43) W.P. 

Although comparative trials have not been conducted, recombinant growth hormone products appear to have similar efficacy for treating growth hormone deficiency. 

Omalizumab is substantially more costly than other AR treatment options and must be administered in the clinic setting.28 Comparative trials are needed to determine the role of omalizumab in AR. 

Several randomized trials have demonstrated that leuprolide and goserelin are effective agents when used alone in patients with advanced prostate cancer.19 Response rates around 80% have been reported, with a lower incidence of adverse effects compared with estrogens.19 There are no direct comparative trials of the currently available LHRH agonists or the dosage formulations, but a recent meta-analysis reported that there is no difference in efficacy or toxicity between leuprolide and goserelin. Therefore, the choice between the two usually is made based on cost and patient and physician preference for a dosing schedule. 

Sneed, Joel R., Bret R. Rutherford, David Rindskopf, David T. Lane, Harold A. Sackeim and Steven P. Roose, Design Makes a Difference A Meta-Analysis of Antidepressant Response Rates in Placebo-Controlled Versus Comparator Trials in Late-Life Depression , American Journal of Geriatric Psychiatry 16, no. 1 (2008) 65-73... 

Gianguzza and Orecchio [147] have carried out comparative trials of various methods for estimating nitrites in seawaters. These workers compared a method using sulfanilic acid/a-naphthylamine complexes with a method using sulfanilamide/N( 1-naphthyl) ethylenediamine complexes for the determination of nitrites in saline waters. The second method has the greater sensitivity and lower detection limits. The former method is subject to interference from chlorides, and this interference can be completely eliminated by the coupling diazotisation procedure of the latter method. 

Despite these potential advantages, clinical experience with vasopressin is limited and comparative trials with epinephrine have produced mixed results. Overall, these studies suggest that vasopressin is effective as part of ACLS after cardiac arrest, but its superiority to epinephrine remains questionable. 

Nonimmunocompromised host Comparative trials for amphotericin Bc versus azoles not available... 

Cerebrospinal fluid shunt procedures 5. aureus, S. epidermidis Cefazolin 1 g every 8 hours x 3 doses or ceftriaxone 2 gx 1 No agents have been shown to be better than cefazolin in randomized comparative trials. IA... 

There are no comparative trials of LHRH agonists, so the choice is usually based on cost (Table 65-1) and on patient and physician preference. Leuprolide acetate is administered daily. Leuprolide depot and goserelin acetate implant can be administered monthly, or every 12 or 16 weeks. 

No direct comparative trials have assessed the effectiveness of one agent over another. Donepezil, rivastigmine, and galantamine are indicated in mild to moderate AD, while donepezil is also indicated in severe AD. 

Results of four placebo-controlled comparative trials have not been as favorable, finding no significant clinical or urodynamic effect for oral estrogen compared with placebo. 

In 1995, Prescrire International, a French journal that evaluates pharmaceutical products, published a review that concluded "As homeopathic treatments are generally used in conditions with variable outcome or showing spontaneous recovery (hence their placebo responsiveness), these treatments are widely considered to have an effect in some patients. However, despite the large number of comparative trials carried out to date there is no evidence that homeopathy is any more effective fhan placebo therapy given in identical conditions." ... 

Ct 1.53 to 1.68 1.41 comparative trial 1980-91, differences already in initial values... 

All relevant comparative trials and on-farm investigations conducted either to observe soil processes after conversion or to improve plant nutrition strategies found ... 

A further example of the ability of doxycycline to penetrate into secretions is provided by a report [53] of a comparative trial of the drug and ampicillin in acute exacerbations in chronic bronchitis. It was found that 100 mg doxycycline daily and ampicillin 250 mg four times daily were clinically equally effective. Bacterio-logically, however, it was found that H. influenzae re-appeared in sputum more often during ampicillin therapy than y ith doxycycline. This was attributed, following earlier workers, to the failure of ampicillin (in the dose used) to reach adequate levels in sputum. By inference, therefore, doxycycline (at one tenth of the daily dosage) achieves adequate levels more readily. 

Comparative trials have shown that each genotoxicity test can generate both false negative... 

Finally, a randomised comparative trial with one alternative marketed medicine can only address the choice between the two. Other comparative trials with other treatments build up a picture of overall therapeutic benefit and risk, and these trials may help to define groups of study subjects who differ in their response from the general population. 

Some disease states or trial conditions militate in favour of a high placebo response rate and lend support for the inclusion of placebo in a comparative trial. These include long treatment periods, previous treatments and response to them, innate characteristics of the study subjects (e.g. social class, educational level and personality t)rpe), influence of medical staff, environment and supervision during the trial, appearance and taste of trial drugs, and presence (or absence) of imwanted pharmacological effects. 

If only active comparator trials were available, then the trial objectives would have to be very precise from the beginning of a trials programme as to whether superiority, equivalence or noninferiority is being tested. Demonstration of... 

There are three possible specific objectives for comparator trials to show superiority, equivalence or non-inferiority of the new active substance. Each is governed by statistical and regulatory guidelines. - 2... 

Fig. 6.5 Power curves this is an illustrative method of defining fhe number of subjects required in a given study. In practice, the actual number would be calculated from standard equations. In this example, the curves are constructed for 16, 40,100 and 250 subjects per group in a two-limb comparative trial. These graphs can give three pieces of information the number of subjects that needs to be studied, given the power of the trial and the difference expected between the two treatments the power of a trial, given the number of subjects included and the difference expected the difference that can be detected between two groups of subjects of given number, with varying degrees of power.

The size of the order for clinical trial medication can be immense, equalling the order for start-up stock for the product when it is eventually launched. It is therefore a major undertaking if the whole requirement for the clinical development programme is ordered at one time however, this is more efficient than placing smaller orders for supplies at irregular intervals. It is also sensible to anticipate the clinical-trial needs after the laimch, when other comparative trials may be sponsored and independent investigators may ask for trial stocks. 

Comparative trials, needed to compete in the marketplace, may require larger populations and longer durations to have sufficient power to determine equivalency or superiority. 

An outline of the data from non-clinical studies must be submitted to the PMDA with the protocol for the proposed clinical study before commencing the clinical trial. A notification is required for each protocol. The list of items required for Clinical Trial Plan Notification is shown in Table 23.4. Furthermore, supplementary data must be added on entry to subsequent clinical phases, that is, general clinical trials and comparative trials. Such data are reviewed by the PMDA, and for this purpose the sponsor must wait for 30 days after submitting the initial notification before executing a contract with the medical institute. For a subsequent notification, the review period is reduced to 14 days. The notification also... 

Yoneda S, Hibino S, Gotoh I, et al. A comparative trial of induction chemoradiotherapy followed by surgery or immediate surgery for stage III NSCLC (abstract 1128). Proc Am Soc Clin Oncol 1995 14 367. 

Fox W, Scadding JG. Medical Research Council comparative trial of surgery and radiotherapy for primary treatment of small-celled or oat-celled carcinoma of bronchus Ten-year follow-up. Lancet 1973 2 63-65. 

GITSG, A multi-institutional comparative trial of radiation therapy alone and in combination with 5 -fluoro uracil for locally unresectable pancreatic carcinoma. The Gastrointestinal T umor Study Group. Ann Surg 1979 189(2) 205-208. 

Furukawa, C. T. (1988). Comparative trials including a beta 2 adrenergic agonist, a methyl-xanthine, and a mast cell stabilizer. Ann. Allergy 60,472-476. 

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