PharmaceuticalOutsourcingQ42020 - 50

CLINICAL TRIALS

standard of care or self-administration of the investigational product,
data can be collected, where under the original protocol these data
would have been missing. These procedural changes will of course
have some impact on the data collected, and analyses may need to
be adjusted to take this into account. It is therefore critical that case
report forms are amended to capture changes to trial procedures at
each data collection, as well as reasons for treatment and/or study
withdrawal. This information can then be considered in the statistical
analyses so that it does not confound the treatment effect.
There is a further consideration in the scenario where there is an
unacceptably large amount of missing data when determining
the number of responders for the primary efficacy endpoint at the
point-in-time of interest. If the original analysis method was based
on a Generalized Estimating Equation (GEE), a weighted GEE could
be considered instead, which would make use of the data from the
preceding visits when computing estimates.

or may not be acceptable is still unfolding. Communication between
departments is therefore key; signals must be raised on anomalies
and they must be opened up for multi-disciplined discussion across
study teams.
One example of anomalous measures in sites which can be captured
by CSM is if a temperature measurement at a particular site differs from
the others due to, for example, incorrectly calibrated thermometers.
Tools such as CluePoints, and SAS JMP can pick up these differences
by analyzing means and variances of temperature readings and
comparing across sites. Without site visits, the need for this kind of
analysis is increased as such differences are less likely to be picked
up. And during these times, analyses should not only be carried out
across different sites but by also comparing, for example, traditional
patient visits to those where they are carried out at a different time or
place due to the pandemic.

Sensitivity analyses may also be included to assess the impact of
intercurrent events using techniques such as multiple imputation.

Conclusion

Improving Data Quality Through
Centralized Statistical Monitoring (CSM)

The COVID-19 pandemic is the biggest challenge the world has faced
in decades; for clinical trial sponsors it is impacting the integrity and
feasibility of ongoing studies as they are threatened by the outbreak's
continuous global spread.

It is likely that access to sites will be restricted for many months
regardless of the trial. This will necessitate the need for alternative
mechanisms to provide monitoring and oversight activities. More
than ever, there is a need for CSM - this is highlighted by recent
guidance from the FDA on conduct of trials during the pandemic: 'If
planned on-site monitoring visits are no longer possible, sponsors should
consider optimizing use of central and remote monitoring programs to
maintain oversight of clinical sites.'
While CRAs are no longer travelling to site, CSM will be required to
check for the usual data patterns and anomalies noted here:

*	 Identify missing data, inconsistent data, data outliers,
unexpected lack of variability and protocol deviations

*	 Examine data trends such as the range, consistency, and
variability of data within and across sites

*	 Evaluate systematic or significant errors in data collection
and reporting at a site or across sites; or potential data
manipulation or data integrity problems

*	 Analyze site characteristics and performance metrics
*	 Select sites and/or processes for targeted on-site monitoring.
However, sponsors must also examine areas not previously required,
e.g. traditional visits versus non-traditional visits and protocol defined
endpoint data collection versus updated endpoint data collection.
When analyzing at site or regional levels, it may be more important to
have some awareness or measure of how far the virus had progressed
at the time of reporting in that region, what measures were being
taken and how regional healthcare systems were coping. Patterns
must be monitored as the trial progresses but with an awareness that
full understanding of the situation, its impact and what results may
Pharmaceutical Outsourcing |

50

COVID-19 is highly disruptive to ongoing clinical trials. The
impact over the coming months and years will be widespread and
multifaceted and it is not possible yet to identify the full extent
and severity of its impact. It is however possible to examine each
study's core components on an individual basis and thus identify
the most affected areas. By putting mitigating strategies discussed
here in place it may be possible to salvage some of, if not all of, a
study's potential.
All the above areas impacted by COVID-19 call for updates to existing
study documentation. It is important to note that these updates can
be made in different ways and should be thought through carefully.
The rapidly evolving situation differs across regions and countries. As
such, protocol amendments or updates to the Analysis Plans will have
to account for this and factor in a level of uncertainty. Sponsors should
also consider the need to document changes to Protocol Deviations
Plans, Analysis of Safety Data and Data Management Plans.
These actions will need punctual documentation and constant
reviewing to ensure they are up to date and aligned with the constantly
evolving situation. This way it will be possible to demonstrate that
the highest standards were pursued and that scientific integrity
and patient safety were safeguarded. With support and cooperation
across the industry, ultimately patients and trial participants can
receive the best possible care.
Karen Ooms is responsible for overseeing the Statistics
department at Quanticate. Karen is a Chartered Fellow of the
Royal Statistical Society and has a background in biostatistics
spanning over 25 years. Prior to joining Quanticate in 1999
(Statwood), Karen was a Senior Statistician at Unilever.
| October/November/December 2020



PharmaceuticalOutsourcingQ42020

Table of Contents for the Digital Edition of PharmaceuticalOutsourcingQ42020

Editor's Message
Editorial Advisory Board
CN Perspectives
Social Media Connections
Insider Insight - Price
Insider Insight - Ventura
Contract Manufacturing
Supply Chain
Contract Manufacturing
Interview with Yourway
Supply Chain
Clinical Trials
Roundtable
Supply Chain
Analytical Testing
Supply Chain
Clinical Trials
Analytical Testing
Horizon Lines
Industry News
Advertiser's Index
PharmaceuticalOutsourcingQ42020 - Cover1
PharmaceuticalOutsourcingQ42020 - Cover2
PharmaceuticalOutsourcingQ42020 - 1
PharmaceuticalOutsourcingQ42020 - Editor's Message
PharmaceuticalOutsourcingQ42020 - 3
PharmaceuticalOutsourcingQ42020 - 4
PharmaceuticalOutsourcingQ42020 - 5
PharmaceuticalOutsourcingQ42020 - Editorial Advisory Board
PharmaceuticalOutsourcingQ42020 - 7
PharmaceuticalOutsourcingQ42020 - CN Perspectives
PharmaceuticalOutsourcingQ42020 - Social Media Connections
PharmaceuticalOutsourcingQ42020 - Insider Insight - Price
PharmaceuticalOutsourcingQ42020 - 11
PharmaceuticalOutsourcingQ42020 - Insider Insight - Ventura
PharmaceuticalOutsourcingQ42020 - 13
PharmaceuticalOutsourcingQ42020 - Contract Manufacturing
PharmaceuticalOutsourcingQ42020 - 15
PharmaceuticalOutsourcingQ42020 - 16
PharmaceuticalOutsourcingQ42020 - 17
PharmaceuticalOutsourcingQ42020 - Supply Chain
PharmaceuticalOutsourcingQ42020 - 19
PharmaceuticalOutsourcingQ42020 - Contract Manufacturing
PharmaceuticalOutsourcingQ42020 - 21
PharmaceuticalOutsourcingQ42020 - Interview with Yourway
PharmaceuticalOutsourcingQ42020 - 23
PharmaceuticalOutsourcingQ42020 - Supply Chain
PharmaceuticalOutsourcingQ42020 - 25
PharmaceuticalOutsourcingQ42020 - 26
PharmaceuticalOutsourcingQ42020 - 27
PharmaceuticalOutsourcingQ42020 - 28
PharmaceuticalOutsourcingQ42020 - 29
PharmaceuticalOutsourcingQ42020 - Clinical Trials
PharmaceuticalOutsourcingQ42020 - 31
PharmaceuticalOutsourcingQ42020 - 32
PharmaceuticalOutsourcingQ42020 - Roundtable
PharmaceuticalOutsourcingQ42020 - 34
PharmaceuticalOutsourcingQ42020 - 35
PharmaceuticalOutsourcingQ42020 - Supply Chain
PharmaceuticalOutsourcingQ42020 - 37
PharmaceuticalOutsourcingQ42020 - 38
PharmaceuticalOutsourcingQ42020 - 39
PharmaceuticalOutsourcingQ42020 - Analytical Testing
PharmaceuticalOutsourcingQ42020 - 41
PharmaceuticalOutsourcingQ42020 - 42
PharmaceuticalOutsourcingQ42020 - 43
PharmaceuticalOutsourcingQ42020 - Supply Chain
PharmaceuticalOutsourcingQ42020 - 45
PharmaceuticalOutsourcingQ42020 - 46
PharmaceuticalOutsourcingQ42020 - 47
PharmaceuticalOutsourcingQ42020 - Clinical Trials
PharmaceuticalOutsourcingQ42020 - 49
PharmaceuticalOutsourcingQ42020 - 50
PharmaceuticalOutsourcingQ42020 - Analytical Testing
PharmaceuticalOutsourcingQ42020 - 52
PharmaceuticalOutsourcingQ42020 - 53
PharmaceuticalOutsourcingQ42020 - Horizon Lines
PharmaceuticalOutsourcingQ42020 - 55
PharmaceuticalOutsourcingQ42020 - 56
PharmaceuticalOutsourcingQ42020 - 57
PharmaceuticalOutsourcingQ42020 - Industry News
PharmaceuticalOutsourcingQ42020 - 59
PharmaceuticalOutsourcingQ42020 - 60
PharmaceuticalOutsourcingQ42020 - 61
PharmaceuticalOutsourcingQ42020 - 62
PharmaceuticalOutsourcingQ42020 - 63
PharmaceuticalOutsourcingQ42020 - Advertiser's Index
PharmaceuticalOutsourcingQ42020 - Cover3
PharmaceuticalOutsourcingQ42020 - Cover4
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