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Table 2 Summary of recommendations

From: Practical guidance for running late-phase platform protocols for clinical trials: lessons from experienced UK clinical trials units

Area in results section

Recommendation

1. Communication

Trial descriptions should be tailored to each audience and each occasion: this is to reduce the (perceived) complexity of a platform protocol where a patient may contribute to only one part of the trial

Clear diagrams are essential to express:

(a) Each individual comparison

(b) The currently-recruiting comparisons

(c) The changes to the open comparisons over time

All patient-facing and ethics committee text should clearly describe:

(a) The current trial

(b) The information which is relevant for the specific participant group

Avoid overloading participants and recruitment teams by using a staged consent process

A trial with a big central team should provide one person as a dedicated point of contact to each site

2. Funding

Funding is likely (to need) to come from multiple sources

Each contribution to funding should aim to include a contribution to the overall infrastructure and the common delivery of the platform

Express to funders both the savings (time, patients, cost) and/or gains (additional scientifically important questions) of using a platform protocol over separate trials

3. Protocol

Choose the most future-proofed option between modular or single approach to protocol development

When choosing whether patients not meeting the eligibility criteria for one comparison could be randomised to other comparisons, consider:

(a) Implications on recruitment

(b) Generalisability of findings

(c) Practical implementation at sites

Explicitly state in the protocol from the outset that future comparisons will be incorporated into the protocol if appropriate

Early engagement and ongoing communication with the regulator is essential

Aim for review by an ethics committee with previous experience and training in platform protocols

4. Database and randomisation system

The database needs to be flexible and scalable

Modular database design with shared elements is preferable if the current or future arms may differ in terms of the information required

Allow for sufficient data management time in each grant. Platform protocols are more efficient in real-time results and input may be required over a shorter time than for any one trial

Ensure choice of randomisation system can incorporate any necessary future amendment (e.g. to eligibility, weightings and stratification factors)

5. Patient and public involvement

Early PPI input improves the design

Support PPI to understand design implications, particularly in adding new comparisons

PPI participation helps the trial team with explanations to ethics committees

Comparison-specific PPI representation can give a more manageable workload for PPI members and enable trial teams to better support PPI members

6. Contracts

Contracts must allow for the longevity of platform trials

Platform protocols are likely to have more external collaborators so allow time for set-up and agreement

7. External trial oversight

Trial oversight committees must expect greater longevity and a considerable workload over time and per meeting, particularly if a platform protocol has many comparisons

Members must be experienced, and any handover should aim to include an overlap period

8. Trial Management Group

The responsibilities of large TMGs may usefully be delegated to specific sub-committees, each responsible for components of the platform

A dedicated lead for each comparison could better support the chief investigator and trial team in development, conduct, and reporting, e.g. comparison CI and comparison co-CI

9. Trial staffing

Flexible staffing allows for more staff at time of higher need

Allow more senior time to manage a bigger team

10. Data management

Data cleaning and checking must be an ongoing process rather than analysis driven, so that all arms are updated fairly

Create a dedicated site advisory team including site representatives

11. Statistical considerations

Choice of single or separate SAPs is driven by which comparisons will be analysed and reported and when they are to be reported (contemporaneously or at different times)

Need to have a senior statistician unblinded and involved in analyses during the trial and another senior statistician who is blinded and unaware of the accumulating data analysis

12. Safety

SAEs must be assessed against the expected events for each of the treatments. Multiple research treatments require additional time at sites and during safety review

Careful management of reference safety information is required with multiple treatments

Multiple groups often need to be notified of SAEs

13. Training

Regularly update training materials and documentation

Make training materials simple and inspiring to avoid site fatigue in long-term protocols with multiple new comparisons and amendments

Make clear to staff that recruitment need not be paused around intermediate analysis

14. Reporting

Aim to give results from across the protocol to all patients, with a contextualising preface specific to their allocation/comparison

Ideally ask whether participants want findings from only “their” comparison, from all comparisons, or no results

CONSORT extensions for multi-arm randomised controlled trials and adaptive trials provide pertinent guidance

Write a publication plan to minimise scheduling clashes for limited staff time

Discuss authorship principles at comparison set-up. Authorship need not be the same for each primary comparison but all relevant names, including all relevant funders, must be noted

15. Adding and closing comparisons

Adding comparisons requires agreement from oversight committees, regulators, and assent from sites

Consider using a checklist in deciding whether to add to the current trial or start a new trial [7]

Aim to close down elements of each comparison as soon as practicable rather than leaving all comparisons open

16. Maintaining relevant control arm treatment

Be prepared for the standard-of-care to change over the lifetime of a platform trial

17. Onward data sharing and re-use

Consider whether data from reported comparisons can be shared on appropriate data release request without compromising ongoing comparisons or planned analyses