Traditionally the focus of pharmaceutical development has been on generating evidence to satisfy regulatory authorities’ assessments of efficacy, safety, and quality. There is increasing focus on the “4th hurdle to market entry” - the assessment by payers of newly approved products. This is based on cost effectiveness – assessment of the value of the incremental benefit provided by a product. One of the challenges in this area is the considerable variation in the evidence requirements across markets. Regional variation also occurs in assessments for the registration of pharmaceuticals, but here ICH does provide harmonisation across the major markets on key principles.
With the added weight of an FDA guidance document and the rapid advancement of the technology available for use, adaptive clinical trial designs are becoming much more appealing. In a nutshell, an adaptive trial involves the ongoing analysis and monitoring of unblinded data by a selected group of independent clinicians and statisticians at defined points during the trial, with the potential for study design changes. Utilising this approach, answers to questions not typically realised before the end of a study can be obtained. For instance; whether certain features of the trial need to be changed, whether the current enrolment target is sufficient to meet the defined statistical endpoints or, possibly, which dose amongst multiple treatment arms will be the most beneficial to the patient. The study team will, therefore, be in a position to propose and take counteractive steps much sooner. The decisions made based on these interim analyses can save on the potential failure of a study due to, for example, incorrect dose choices or miscalculated sample sizing and ensure that the chances of a successful study are optimised.
A common theme from this year’s PhUSE was how Pharma and CRO companies are implementing efficiencies to all programming functions. Much of this stemmed from the use of standardised database designs (including CDASH standards) to build a Meta-data Repository (MDR) which promotes reusability across studies from SDTM mapping to define xml generation and much more (presentations: SI01 / DS11 / DH05). Some of the processes involve bespoke in house tools and/or fulltime standards teams to make this work but the huge effort looks to be rewarded with efficiency on the various study tasks.
This year’s annual conference for the SCDM took place in Orlando. The venue was fortunately spared the forces of Hurricane Irma. Hurricane Maria had also threatened the area for the opening ceremony, but veered off into the Atlantic and left us to enjoy a very full programme of oral and poster presentations, panel and round table discussions and exhibitions.
The keynote presentation gave an insight into the FDA’s perspectives on clinical trials conducted outside the U.S. The talk discussed how European guidelines and directives and the GCP requirements for validation of data obtained through onsite inspections to assure data quality, integrity, and development of medical products were evaluated from an FDA perspective. The SCDM are actively widening their presence outside the US and, together with presentations of this nature, will undoubtedly bring a wider appreciation and understanding of managing international clinical trials to their predominantly US based membership.
SAS Programming Tip For Categorising Calculated Values
We derived a % result based on 2 values, using the simple formula based on a post and pre assessment:
For 2 patients, we ran into issues when the following values were used:
subject 001: AVAL = (0.84-0.75)/0.75*100 = 12
subject 002: AVAL = (1.38-1.2)/1.2*100 = 15