CROSS Research’ Biometry Unit provides in house Clinical Data Management and the full range of Medical Statistics, Biometric and Pharmacokinetic analysis.

The acquired expertise of its team allows undertaking statistical consultancy to manage projects across different study types and across a wide range of therapeutic areas.

Designing clinical trial is vital to ensure that the study leads to unbiased conclusions ending up with valid results and is compliant with ethical guidelines.

CROSS Research is an active member of the CDISC consortium (at present with a Gold Membership status) and can provide professional up to date advice on a wide range of aspects concerning clinical trial designs and data management.

Data Management

 

CROSS Research performs data handling using a fully validated, FDA 21 CFR Part 11 compliant, proprietary, ORACLE based clinical data management system, DM Services include:

  • CRF Design and Production
  • Database Design and Validation
  • Data Entry Screens
  • CRF Log and Tracking
  • CRF Review
  • Double Data Entry and Verification
  • Programming and Validation of Edit Checks
  • Data Clarification Forms Generation and Resolution
  • Data Clarification Forms Processing
  • Electronic Audit Trail Generation
  • AEs, Medical History and Concomitant Medication Coding
  • Data Quality Reviews
  • Database Lock and Freeze
  • Database Status Updates
  • SDTM programming
  • Archival
The accuracy of the data entry performed during the DM process is verified by an independent secondary entry and a subsequent comparison of the datasets generated to highlight discrepancies. The data are then validated electronically using validation check programs, and data clarification forms are produced and solved. At the end of the process the database is audited against the CRFs.

Statistics

 

After a Quality Control (QC) review, the database is exported to SAS (typically in SDTM domains) in order that the data listing, statistical summary and analysis programming can take place to produce the Tables, Listings and Graphs (TLGs) for inclusion in the Statistical Report (SR) and in the Clinical Study Report (CSR). TLGs undergo QC and validation by independent programming of the same summary statistics and analyses. Discrepancies are then resolved.

CROSS Research offers Statistical services which includes:

  • Analyses of parallel group  and crossover trials
  • Analyses specific to crossover designs
  • Longitudinal data analysis
  • Survival data
  • Comparative studies
  • Equivalence/non-inferiority hypotheses
  • Parametric and non-parametric analyses
  • Hierarchical modelling
  • Meta-analyses
  • Repeated measures analyses
  • Multiple regression
  • Analysis of Variance and Covariance
  • Survival/failure analysis (including Cox regression)
  • Generalised linear models
  • Logistic Regression
  • Multiple comparison techniques
  • Biostatistical modelling
  • Monte Carlo methods
  • Simulation
QC process in place for the statistical summary and analysis ensures that SAS programs are validated for the production of TLGs by checking that all the study requirements were addressed. QC also confirms that the statistical analysis plan (SAP) was written following SOPs and that all SAPs have the appropriate approvals.

Consulting Services

 

Besides the full range of DM and Statistical Services, CROSS Research provides a huge range of consulting services, which includes:

  • Protocol development and review
  • Sample size calculations
  • Randomisation list and envelopes and code break envelope generation
  • CRF advice, design and review
  • Working alongside EDC systems
  • SAP preparation, include table blanks
  • Executive and full statistical reports
  • Integrated summary of efficacy and safety
  • Post-hoc and exploratory analysis
  • Representative for client at Regulatory Agencies meetings
  • Safety and efficacy summaries for regulatory submissions
  • Performing interim analyses and defining stopping rules
  • Providing independent statistician

PK analysis

 

CROSS Research specializes in conducting pharmacokinetic data analysis for clinical studies. We perform either model dependent (Compartmental) or model independent (Non-Compartmental) analyses using a validated WinNonlin system.

Non-compartmental Analysis (NCA) of Phase I studies provides the PK results needed for a large array of assessments, Average Bioequivalence (ABE), Reference-Scaled Average Bioequivalence (RSABE), food effect, drug-drug interaction, special population PK, drug exposure and drug recovery data. Assessments of PK/PD relationships can be also provided.

Regulatory support in Pharmacokinetics

CROSS Research team, taking advantage of more than 20 years spent in drug development, can provide the advice and support necessary to move forward your pharmacokinetic programs. Solutions are provided through several possibilities: designing appropriate PK studies, performing predictive calculations or power analysis, properly evaluating guidelines, assessor’s requests and incorporating pharmacokinetic and clinical pharmacology technical summaries for regulatory submissions.

Pharmacokinetic Simulations

Basing on the existing PK data, simulation analyses to predict the plasma concentration profile of a drug under different conditions can be performed. This information allows previewing the potential effect of various routes of administration, multiple dosing regimens, and variable infusion schedules. These simulations can provide valuable insight into the design of preclinical and clinical studies.