PharmaceuticalOutsourcingQ42020 - 49

SECTION
TITLE
CLINICAL
TRIALS

or predictive power, depending on whether you root for frequentist
or Bayesian statistics) given the current data. Using this information
(yet considering all available patient-level data) the Data Monitoring
Committee can make a better decision as to whether the study is still
likely to succeed or not.
The advantage of this approach is that only studies that are
reasonably likely to deliver positive results, and for which no
safety concerns arise, will continue, thus freeing up resources for
other projects and minimizing unnecessary efforts on all sides. It is
relevant to point out that going down this route has implications
on study design: if an unblinded interim is added, preservation of
type I error rate needs to be maintained via, e.g., alpha-spending
functions that ultimately imply an increase in the overall sample
size. While this might seem counter-productive, considering the
difficulties in achieving the planned, and lower, sample size, this
ensures that the efforts of recruiting additional patients are only
done for promising compounds.

Estimands and Missing Data: Is COVID-19
an Intercurrent Event?
In normal circumstances, intercurrent events should be outlined in
the protocol and the estimands defined to outline the approach to
each anticipated intercurrent event. In these extraordinary times it
is expected that protocol amendments will be written to document
changes to the design and conduct of studies. This acknowledges
adaptations to travel restrictions, limited access to sites, subjects and
site staff suffering from COVID-19. It therefore seems reasonable to
review and adapt study estimands as well.
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49

Protocols may be adapted to allow for a pause in treatment, an
alternative treatment, remote visits, larger visit windows and so
on. Subjects may miss visits due to logistical reasons or having the
virus. Each of these situations can be treated as an intercurrent
event and, for each, the most appropriate strategy selected. The
most suitable approach will depend on the details of the trial, the
study treatment and the indication, and will need to be agreed by
the whole study team. Consequently, adaptations may be required
to the planned analyses to ensure consistency with the estimands
defined in the protocol.
Depending on which strategies are used for COVID-19 related
intercurrent events, there will potentially be an increase in missing
data. Updates to the approach to dealing with missing data may be
required to ensure it is appropriately dealt with and consistent with
the estimands.
In the simplest scenario, where only minimal changes to the trial
conduct have been, or need to be, implemented, it might be
reasonable and acceptable not to treat events related to COVID-19
as intercurrent events. In this scenario, the practical impact would
simply be a larger than previously anticipated amount of missing
data, and this can be tackled by amending the missing data approach
outlined in the Statistical Analysis Plan, or by justifying the reasons
for no changes.
Trials are ideally designed with the intention of minimizing missing
data. In this situation, adaptations will be required as a reaction
to the pandemic, as the need to minimize the amount of missing
data is fundamental. By, for example, making some changes at the
procedural level such as making use of local labs or switching to
| October/November/December 2020


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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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