Equivalence therapeutic

80 and 1.25. This requirement applies to both AUC and A deviation from the rules for therapeutic equivalence is that 90 per cent confidence intervals are used rather than 95 per cent leading to a more relaxed requirement. 

The reason why ratios of geometric means are used in this context is as discussed in Section 11.4 the distributions of AUC and tend to be positively skewed and the log transformation is applied to recover normality. 

By taking logs, the above condition, 0.8 1.25, can be translated into the 

The rules for therapeutic equivalence are different from those for bioequivalence. The choice of margin will be a mixture of statistical and clinical reasoning. Strict equivalence is appropriate when we want to consider essential similarity or where the test treatment is to be used as an exact replacement for the new treatment. In these cases A should be chosen to be a completely irrelevant difference from a clinical point of view. Ebbutt and Frith (1998) based their choice of A= 15l/min on several considerations  

In the next section we will discuss the non-inferiority setting and many of the considerations there also apply to the situation of equivalence. 

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Approved Prescription Drug Products, with Therapeutic Equivalence Evaluations, Bureau of Dmgs, Pood and Dmg Administration, U.S. Dept, of Health and Human Services, Bethesda, Md., 1980. 

Levothyroxine (Synthroid , Levoxyl , Unithroid ), other brands, and generics Synthetic LT4 25, 50, 75, 88, 100, 112, 125, 137, 150, 1 75, 200, and 300 meg tablets 500 meg vial for injection 60 meg Gold standard for treating hypothyroidism products not therapeutically equivalent full replacement dose 1-1.6 meg/kg per day when switching from animal product, lower calculated daily dose by 25-50 meg intravenous form rarely needed... 

More important than bioequivalence is the therapeutic equivalence of LT4 products. Will patients have the same outcomes if bioequivalent products are used The study by Dong... 

Often it is unnecessary to calculate an exact value for an absorption rate constant. For example, when several oral tablets containing the same drug substance are all found to be completely absorbed, it may be sufficient to merely determine if the absorption rates are similar to conclude that the products would be therapeutically equivalent. In another instance, it would be possible to choose between an elixir and a sustained-release tablet for a specific therapeutic need without assigning accurate numbers to the absorption rate constant for the two dosage forms. 

T. B. Casale, S. M. Azzum, R. E. Miller, and J. Oren, Demonstration of therapeutic equivalence of generic and innovator beclomethasone in seasonal allergic rhinitis, Ann. allergy Asthma Immunol, 82, 435 (1999). 

P. A. Meredith, Generic drugs therapeutic equivalence, Drug Safety, 15, 233 (1996). 

Electronic Orange Book, Approved Drug Products with Therapeutic Equivalence Evaluations, [Internet]. URL http //www.fda.gov/cder/ob/default.htm, accessed 7-29-2000. 

There are three levels of equivalence for classifying products, each submitted to an identical maximum level of public financing chemical equivalence, pharmacological equivalence and therapeutic equivalence. The first level entails establishing groups for the same active ingredient, which at the same time include both generics and brand-name pharmaceuticals whose patent has expired. This is the system applied in Sweden, Denmark, Norway and Spain. It encompasses bio-equivalent products with identical qualitative or quantitative composition, pharmaceutical form, dose, administration method and presentation . 

Medical scientists mainly rely on the measurement of bioavailability of a drug as a positive indicator of therapeutic equivalence, because clinical efficacy for orally administered drugs depends on the degree of absorption and the presence of the active ingredient in the blood stream. 

Salvador M, Holzer H, de Mattos A, Solhnger H, Ams W, Oppenheimer E, Maca J, Hall M. (2004) Enteric-coated mycophenolate sodium is therapeutically equivalent to mycophenolate mofetil in de novo renal transplant patients. Am J Transplant 4 231-236. 

Orange Book means the FDA s publication entitled Approved Drug Products with Therapeutic Equivalence, in which the patents claiming a drug product approved through an NDA are listed. 

The Bureau of Competition and Policy Planning Staff of the Federal Trade Commission ( FTC ) submit this Citizen Petition to the Commissioner of Food and Drugs pursuant to 21 C.F.R. 10.25(a) and 10.30 concerning certain issues relating to patent listings in the FDA s Approved Dmg Produets with Therapeutic Equivalence Evaluations (the Orange Book ). We request that the FDA clarify these issues, on an expedited basis, via industry guidanee or other means that the FDA considers appropriate. 

See FDA, Prefece to Twenty First Edition of Approved Drug Products with Therapeutic Equivalence Evaluation,... 

Brand interchange - The metolazone formulations are not bioequivalent or therapeutically equivalent at the same doses. Mykrox is more rapidly and completely bioavailable. Do not interchange brands. 

Because of high bioavailability, oral and IV doses are therapeutically equivalent, so patients may be switched to and from the IV form with no change in dose. 

Bioequivalency The sprinkle formulation is bioequivalent to the immediate-release tablet formulation and, therefore, may be substituted as therapeutically equivalent. 

Premarin is derived from pregnant mare s urine Cenestin from yams and soy. Although probably therapeutically equivalent, they are not substitutable by the pharmacist... 

Bioequivalence problems have been documented in the past for products marketed by different manufacturers however, studies in patients have shown comparable clinical efficacy between brands based on the results of thyroid function tests brand interchange should be limited to products with demonstrated therapeutic equivalence... 

In therapeutic equivalence trials and in non-inferiority trials we are often looking to demonstrate efficacy of our test treatment indirectly. It may be that for ethical or practical reasons it is not feasible to show efficacy by undertaking a superiority trial against placebo. In such a case we compare our test treatment to a control treatment that is known to be efficacious and demonstrate either strict... 

Equivalence trials are, of course, routinely used in the evaluation of bioequivalence and the methodology there is well established, both European and FDA guidelines exist. More recently we have seen the need to establish therapeutic equivalence and Ebbutt and Frith (1998) provide a detailed case study in the development of an alternative propellant for the asthma inhaler. More usually,... 

Similar comments apply to therapeutic equivalence trials also. 

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