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The Benefits of Individualized Dosing

The Benefits of Individualized Dosing

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Individualized dosing has been shown to have such a significant effect on patient outcomes that it is recommended by the Australian Therapeutic Guidelines, and is supported by a Cochrane Review showing both increased therapeutic effect and decreased side effects.

The following papers are split into three sections: improved outcomes, reduced adverse events, and reduced costs.

IMPROVED OUTCOMES

The following papers are just some of the randomized controlled clinical trials that show the patient benefits of dose-individualization:

  1. Increased survival for childhood leukemia patients.
  2. Improved survival for septic patients.
  3. Increased patients in therapeutic range (chemotherapy).
  4. Increased proportion of patients in therapeutic range:
    1. Warfarin
    2. Enoxaparin1
    3. Vancomycin
    4. Aminoglycosides
  5. Decreased time to therapeutic stabilization.
  6. Shortened febrile periods:
    1. Gentamicin
    2. Aminoglycosides

REDUCED ADVERSE EVENTS

Dose-individualization reduces adverse events. The following RCTs demonstrate some of these benefits:

  1. Reduced risk of toxic drug levels.
  2. Reduction in bleeding events.1
  3. Reduction in bruising events.1
  4. Halve side-effects for chemotherapy patients.
  5. Decreased discontinuation due to adverse events.
  6. Decreased nephrotoxicity:
    1. Gentamicin
    2. Vancomycin

REDUCED COSTS

Improving patient outcomes and reducing adverse events is highly cost-effective. The studies below quantify the cost-benefits of individualized dosing:

  1. Cost-benefit ratio of between 4:1 and 52:1. (Review).
  2. Save $2,500 (USD, 2012) per patient.
  3. Substantial overall savings due to lowered mortality.
  4. More than 6 day reduction in hospital stay length.
  5. Halve the number of assays required.

“[Aminoglycoside Bayesian dose individualization] is a well-accepted practice… [Further studies] may not be feasible for ethical reasons.” – Ho et al.

Bayesian dosing has been shown to have such significant benefits that some leading researchers believe that further clinical trials may be unethical, due to the control arm being required to receive substandard treatment.

  1. Note that these studies were not Bayesian dose individualization, but a less-sophisticated method. Bayesian dosing compared to population-based methods has been shown to be significantly more effective. (van Lent-Evers et al. 1999; Matthews, I et al., 2004). ↩︎