A key aspect of clinical trial operational success is getting the right data. Dr Michael Silverman, principal at BioStrategics Consulting Ltd., discusses managing clinical assessments and laboratory procedures to ensure the quality of data acquisition.
Last week I discussed operational success from the viewpoint of Getting the Right Data and specifically choosing the right clinical sites. This week I would like to discuss Getting the Right Data from the standpoint of standardized clinical assessments, centralized laboratory procedures, managing clinical supplies, and managing biological specimens.
Standardizing Clinical Assessments
It is absolutely imperative that those clinical assessments that are critical to study outcome be measured the same way at every site, for every patient, at every time point. This requirement means that outcomes measures should be made objective to the extent possible; that all investigators will be trained to use standardized diagnostic techniques; and that, when relevant, the same diagnostic equipment be used at each site.
For example, in a clinical trial of glaucoma therapy, the primary end point of drug therapy is intraocular pressure. A variety of techniques exist for measuring pressure, and even the same technique may encompass several different machines having different calibrations, performance criteria, and normal ranges. Failing to standardize procedures across sites creates enough noise to obscure any signal coming from the drug. Standardization can be achieved relatively easily by providing the same model tonometer and the same training to all investigators.
Centralized Laboratory Procedures
Similar considerations apply to laboratory testing procedures, all the way from routine hematology testing to exotic genetic sequencing of, for example, an HIV isolate. Sponsors often utilize centralized laboratories for routine samples in clinical trials, a measure that not only ensures standardization of analysis procedures but also simplifies the statistical calculations at the end of the trial. Even if local laboratories are used for something as straightforward as determining hemoglobin and hematocrit levels in patients treated with recombinant human erythropoietin, care must be taken to ensure that data from all laboratories conform to the same analytical standards.
A closely analogous, but more complex, situation arises when the clinical end point relies upon a diagnostic parameter that includes human interpretation and, inevitably, a subjective component: histology, vascular imaging, electrocardiography, computerized tomography, and the like. In such situations, the most efficient and reliable route to standardization is the use of a centralized reading panel. In a study of cervical dysplasia treatment, three expert gynecologic pathologists were impaneled to read initial and final biopsy slides from all patients at all sites, thus ensuring that the same interpretive criteria were universally applied.
Managing Clinical Supplies
Integrity of clinical supplies is critical. In a blinded trial, poor labeling of clinical supplies can lead to the substitution of one dosage strength for another – completely confounding trial results and costing the sponsor significant loss of time and money. In another example, a delay in supplying some sites with -20 degree C freezers could result in unrecognized temperature-induced drug inactivation, an event whose effect on trial results would be disastrous.
Managing Biological Specimens
Just as management of clinical supplies ensures integrity of what goes into the patient, management of biological specimens does the same for what comes out of the patient – and may be critical to operational success of the trial. For example, in a first-in-man trial of a viral vector, a living biological agent with potential therapeutic effects, critical blood level data could be obtained only by culturing the vector from serum samples. Mishandling of the blood, by exposing it to heat or ultraviolet light, could inactivate the virus and render it nonviable on culture. Should such an event occur, an artifact induced by poor ex vivo study procedures would be misinterpreted as absent blood levels – severely skewing the interpretation of the trial.
Dr Michael Silverman is the principal clinical consultant at BioStrategics Consulting Ltd., a clinical development consulting company based in Marblehead, MA, with business interests around the globe. Dr Silverman would be delighted to hear your thoughts on today’s blog, your experiences, or anecdotes and of course, your questions. To make comments or ask questions, click on this link.
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