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Related Concept Videos

Bioequivalence Experimental Study Designs: Repeated Measures, Cross-Over, Carry-Over, and Latin Square Designs01:15

Bioequivalence Experimental Study Designs: Repeated Measures, Cross-Over, Carry-Over, and Latin Square Designs

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Bioequivalence experimental study designs play a pivotal role in testing the effectiveness of various treatments. Key among these are the repeated measures, cross-over, carry-over, and Latin square designs. In the repeated measures design, each subject receives all treatments, allowing for temporal comparisons. This type of design is useful in reducing variability but requires careful planning to avoid bias.The cross-over design, an economical method, involves sequential administration of...
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Bioequivalence Experimental Study Designs: Completely Randomized and Randomized Block Designs01:20

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Bioequivalence experimental study designs are crucial methodologies used in evaluating and comparing the bioavailability of different drug products. These designs are categorized into various types: completely randomized, randomized block, repeated measures, cross and carry-over, and Latin square designs.Completely randomized designs involve randomly allocating treatments to all subjects participating in the experiment. This allocation is achieved by assigning unique random numbers to subjects...
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Bioequivalence studies: Biowaivers01:13

Bioequivalence studies: Biowaivers

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In certain scenarios, in vitro dissolution tests can replace in vivo bioequivalence studies. This is particularly true when a drug product, though available in varying strengths, maintains proportional similarity in its active and inactive ingredients. In such cases, the need for in vivo bioequivalence studies for lower strength variants may be waived, provided dissolution tests and in vivo studies on the highest strength yield satisfactory results.Bioequivalence can be indicated through...
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Bioavailability Study Design: Single Versus Multiple Dose Studies01:11

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Bioavailability studies are essential for understanding how a drug is absorbed, distributed, metabolized, and excreted in the body. These studies assess the extent and rate at which the active pharmaceutical agent becomes available at the site of action. The design of bioavailability studies can involve single-dose or multiple-dose regimens, each with distinct advantages and limitations.Single-dose studies are the preferred approach due to their simplicity and reduced drug exposure for...
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Crossover Experiments01:16

Crossover Experiments

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Crossover experiments, also called the repeated-measurements design, is a study design in which all experimental units are exposed to all treatments in different periods. Crossover experiments are generally used in psychology, the pharmaceutical industry, agriculture, and medicine.
Crossover designs are performed even with smaller sample sizes since the samples can act as their controls. These are better than simple randomized trials since patients are exposed to all the treatments.
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Bioequivalence of Drugs: Drugs with Multiple Indications01:09

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The concept of therapeutic equivalence (TE) in drugs with multiple indications is complex. A generic drug may be therapeutically equivalent to a brand-name product for one specific indication, but this doesn't necessarily mean it's equivalent for all other indications. Evidence of TE in one patient group and bioequivalence shown in healthy volunteers can support—but not confirm—TE for other indications. However, definitive proof requires individual clinical studies for each...
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Related Experiment Video

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A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition
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Two-stage designs in bioequivalence trials.

Helmut Schütz1

  • 1BEBAC, Neubaugasse 36/11, 1070, Vienna, Austria, helmut.schuetz@bebac.at.

European Journal of Clinical Pharmacology
|January 22, 2015
PubMed
Summary

Non-fixed sample size designs, particularly two-stage adaptive approaches, offer ethical and economical alternatives for bioequivalence trials. These validated designs maintain statistical power and type I error rates, improving efficiency.

Area of Science:

  • Clinical Pharmacology
  • Biostatistics
  • Drug Development

Background:

  • Fixed sample size designs are standard in bioequivalence trials.
  • Non-fixed sample size designs, including adaptive approaches, are gaining regulatory acceptance.
  • Assessing the risks and benefits of these flexible designs is crucial.

Purpose of the Study:

  • To evaluate the current status of non-fixed sample size designs in bioequivalence trials.
  • To focus on the application and implications of two-stage adaptive designs.
  • To compare different methods for their impact on patient and producer risks.

Main Methods:

  • Comprehensive literature search of PubMed and Google Scholar (inception to October 2014).
  • Review of publicly available regulatory guidelines for bioequivalence studies.

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  • Monte Carlo simulations to compare various non-fixed sample size design methods.

    • Main Results:

    • Add-on, group sequential, and adaptive two-stage designs are regulated for bioequivalence.
    • Inappropriate application of these designs can increase patient risk.
    • Adapting based on the first-stage T/R ratio requires careful consideration.
    • Published two-stage designs generally preserve type I error and power.

    Conclusions:

    • Validated two-stage designs can be used without requiring sponsor simulations.
    • These designs offer improved power based on additional assumptions.
    • Two-stage designs present ethical and economic advantages over fixed sample size designs.