Equivalence clinical

Intranasal 17 /J-estradiol spray is given once or twice daily, and is clinically equivalent to oral or transdermal estradiol, but causes less mastalgia. 

In a cost-benefit analysis, both costs and consequences are valued in dollars and the ratio of cost to benefit (or more commonly benefit to cost) is computed. Cost-benefit analysis has been used for many years to assess the value of investing in a number of different opportunities, including investments (or expenditure) for health care services. Cost-effectiveness analysis attempts to overcome (or avoid) the difficulties in cost-benefit analysis of valuing health outcomes in dollars by using nonmonetary outcomes such as life-years saved or percentage change in biomarkers like serum cholesterol levels. Cost-minimization analysis is a special case of cost-effectiveness analysis in which the outcomes are considered to be identical or clinically equivalent. In this case, the analysis defaults to selecting the lowest-cost treatment alternative. Cost-utility analysis is another special case of cost-effectiveness analysis in which the value of the outcome is adjusted for differences in patients preferences (utilities) for the outcomes. Cost-utility analyses are most appropriate when quality of life is a very important consideration in the therapeutic decision. 

Fig. 8.9 Relationship between statistical and clinical significance in clinical equivalence studies.

However, another large meta-analysis study found no difference between different viability testing methods for predicting survival after revascularization, suggesting that decisions driven by viability studies are clinically equivalent and have similar outcomes, irrespective of the technique used [88]. While improved LV function is a major factor affecting... 

Tablets and solution are not bioequivalent (tab has 27% > bioavailability) however, 2-mg tabs clinically equivalent to 2 mg oral sol not known if higher doses of oral sol are clinically equivalent to higher doses of tabs... 

As seen in Figure 12.1, this confidence interval is completely contained between the equivalence margins —151/min to 151/min and all of the values for the treatment difference supported by the confidence interval are compatible with the definition of clinical equivalence we have established equivalence as defined. 

In this case, the alternative hypothesis states that the two treatments are clinically equivalent the null hypothesis is saying that the two treatments are not equivalent. Note that the alternative encapsulates the objective we are trying to disprove the null in order to establish equivalence. 

Kesselheim AS et al Clinical equivalence of generic and brand-name drugs used in cardiovascular disease. A systematic review and meta-analysis. JAMA 2008 300 2514. [PMID 19050195]... 

COMPARABILITY NEEDS Physiochemical Equivalence Biological Activity Physiochemical Equivalence Biological Activity +/- Animal PK Studies Physiochemical Equivalence Biological Activity Clinical Equivalence NONE... 

The sponsor may wish to make specific claims in the package insert that no drug-drag interaction is expected. In these instances, the sponsor should be able to recommend specific no effect boundaries, or clinical equivalence intervals, for a drag-drag interaction. No effect boundaries define the interval within which a change in a systemic exposure measure is considered not clinically meaningful. 

There are in general, two t5rpes of equivalence trials in clinical development, bio- and clinical equivalence. In the former, certain pharmacokinetic variables of a new formulation have to fall within specified (and regulated) margins of the standard formulation of the same active entity. The advantage of this type of trial is that, if bioequivalence is proven then proof of clinical equivalence is not required. Proof of clinical equivalence of a generic product to the marketed product can be much more difficult to demonstrate. 

Bioequivalence of metered dose inhalers and other inhaler devices may be established from data establishing physical and clinical equivalence. 

The role of solute removal in defining adequacy of PD is complicated by the concern that solute removal by PD may not be clinically equivalent to an equal quantitated solute removal by RRF. For PD, small solute clearance targets have often been established on the assumption that peritoneal and renal clearances are equivalent and therefore additive. However, most studies that exammed the relationship between small solute clearances and mortality rates noted that patient survival was directly correlated with renal clear-... 

Finally, apatient quality-of-life assessment should be performed regularly. Agents that appear clinically equivalent may differ substantially in resulting quality of life. Inquiry should be made regarding general well-being, emotional function, and social function. Social function may include assessment of the ability to perform routine... 

Mattsson LA, Christiansen C, Colau J, et al. Clinical equivalence of intranasal and oral 17/i-estradiol for postmenopausal symptoms. Am J Obstet Gynecol 2000 182 545-552. 

Carvedilol is clinically equivalent to isosorbide in angina of effort... 

A 1-year randomized double-blind study in 639 type 2 diabetic patients [13] showed clinically equivalent improvements in glycaemic control for the combination therapy of metformin and SU (HbAlc decrease 1.36%) or pioglitazone and SU (HbAlc decrease 1.20%). Pioglitazone addition to SU significantly reduced triglycerides (-16% vs. -9% p = 0.008) and increased HDL-cholesterol (14% vs. 8% p < 0.001) compared with metformin... 

These studies clearly have to be of sufficient size to avoid type II (statistical) errors and confirm that the two products are truly clinically equivalent. 

Differences in the formulation for HFC MDIs can lead to differences in the amount of drug deposited in the lung and also where it is deposited. Pharmaceutical data may not predict with precision the relative potency or the therapeutic ratio in patients. For example, Qvar (3M), the only formulated HFC beclomethasone with published information, has a smaller particle size, and radiolabeling data show that up to eight times the dose is delivered to the lungs, while three times less is delivered to the oropharynx (9). Clinical studies have shown that Qvar is equivalent to twice the dose of CFC beclomethasone (10,11)— i.e., the dose will need to be halved when transition occurs. In contrast, HFC fluticasone (Glaxo Wellcome) more closely resembles the CFC version, and studies have shown clinical equivalence at the same dose (12,13). 

Kampe S, Wolter K, Warm M, Dagtekin O, Shaheen S, Landwehr S. Clinical equivalence of controlled-release oxycodone 20 mg and controlled-release tramadol 200 mg after surgery for breast cancer. Pharmacology 2009 84 276-81. 

With the preparation of medicines the pharmacist has some freedom to choose excipients. The active substance should however be identical to those mentioned on the prescription. Sometimes there are pharmaceutical reasons, for example the stability of the product, to change the active substance for a more appropriate clinically equivalent substance. 

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