Posology for Regenerative Therapy
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Sola dosis facit venenum (The dosage makes it either a poison or a remedy)
The science of dosage or posology (from Greek posos, how much, and logos, study) is a branch of pharmacology and therapeutics concerned with treatment dosage and dosage regimen. Establishing optimum dosage underpins every clinical development plan for novel therapeutic candidates. Failure to select the adequate drug dose is a leading culprit for regulatory delays or denial of initial applications for new drugs and, more generally, inadequate dose selection contributes to the high attrition rate of pivotal clinical trials.1
Article, see p 1279
Regulatory agencies are committed to facilitate the development and ultimate licensure of safe and effective regenerative therapies.2 To this end, dedicated programs applicable to stem cell therapies have been designed to expedite the advancement and approval of new products (eg, breakthrough therapy designation, accelerated approval).3 However, with limited grasp on the disposition (pharmacokinetics) and action (pharmacodynamics) of stem cells, posology applied to the development of cardiovascular regenerative therapies is still a nascent area of investigation.
Without the establishment of standardized dose regimens, clinical trials continue to evaluate wide dose ranges.4 A case in point are clinical studies that have shown rather paradoxical results about the relationship between the stem cell dose and clinical benefit in the setting of heart disease.5 Accordingly, scientific, regulatory and medical communities remain challenged with critical gaps …