All should be part of the study team or be at least informed before the kick-off. This ensures, that all relevant questions are asked and considered at the right time point. 

How much and how frequent the engagement amongst all internal departments is strongly depends on the company. However, all departments should be included at the beginning and then be invovled again, as soon as the respective questions arise and need to be considered at. 

If the design is novel Ethic Boards should be engaged as early as they can provide valuable insights and improve the submission and approval process. This should be considered on a study by study basis. Furthermore views may differ depending on different countries. So for global studies there may be value in egageing ECs in each country, even though this is labour intense.

All Ethics related questions that might come up within novel appraoches should be discussed to enable a proactive management of the study team towards potential ethical questions and challenges.

Engagement should ideally be frequent during protocol developement but defintley early in study set-up in order that their advice can be taken into consideration.

Regulatory boards should be contacted as soon as a pragmatic trial is discussed within a company to ensure full understanding and support. The latest timepoint should be during the early design phase.

Establish of a mutually agreeable plan: ensure that study will meet all necessary requirements and will be accepted by regulatory agency (e.g. safety monitoring). Also get the assurance that the execution of a pragmatic trial will not delay the approval process, ie that there will not be a retroactive request to include that trial data into the submission package.

Frequency of update depends on the demand of regulatory agency.

Depending on the country and study: ~ 1 year ahead of patient recruitment.

Ensure that data is actually meeting the needs and requirements of HTA agencies.

Frequency of update depends on the demand of HTA agency.

In the commercial sector the Market Access personel would obtain knowledge on what data payers want and when on an ongoing basis during asset development (this might be done in parallel to establishing contact to the HTA agencies).

What data to support pricing discussions and when is it needed.

In the commerical sector this would be on a ongoing basis. There would be shared learning's across assets and therapy areas and then specific feedback would be sought when needed.

At least 1 year ahead of study patient recruitment.

Often pragmatic trials require increased resourcing. CROs may be hired to take over study specific tasks, such as pharmacy and GP monitoring, training etc. They will need enough time upfront to build their capabilities and to build relationships etc. 

Continuously.

At time of concept/draft protocol.

Support on the operational level:patient management as described in the protocol should meet the standard of care in the specific country the study is executed in. To ensure meeting SoC, practitioners guidance and consultation is needed.

During protocol writing there probably needs to be continuous alignment to discuss and incorporate changes that are made to the protocol. After writing the protocol the study execution team will get feedback from participating practitioners, so extra engagement will probably not be needed.

Ideally, patient involvement should be sought for from the very beginning of the research process, so as to ensure that their input is used to identify research questions that matter to patients’ communities. That said, patient engagement should be nurtured throughout the whole process. To ensure that, a key role could be played by patients organisations, which might act both as first point of contact and gateways between the research team and the patient community.

Patient engagement can and should be pursued around multiple areas and questions.

Research Questions and Methods:
Patients need to be informed as to the objectives that a given research programme aims to achieve, the advancement it will bring along if successful, and how patients can realistically contribute to the development of the research process. Once these methods are identified, appropriate structures should be put in place to enable patients to make their contribution.

Expected benefits:
Absolute clarity is needed at the beginning as to the nature of expectations that patients should have when joining the trial. Also, equal clarity is needed with regard to who is going to most benefit from a specific trial (those who join or future patients?)

Recruitment and Randomization:
Adequate patient engagement can benefit recruitment rates. Adequate information should be provided about (and patients perspectives should be sought for in relation to) the way the randomization process is performed (comparator, implications, monitoring).

Post-trial stage:
If well-functioning mechanisms of researcher-patient accountability are to be in place, patient engagement should not finish once the trial has come to an end. IAPO focus groups reveal that patients are particularly unhappy as to the way in which post-trial communication is handled. Questions such as: What has the trial achieved? What improvements have the study participants helped researcher achieve? What are the practical implications of the trial? often remain unanswered. Yet these are crucial aspects at which patients look to develop an opinion on the degree of usefulness of research.

No suggested frequency as long as the conditions are created for patient’ engagement to take place at all levels and stages.

Depending on previous experience. In the abscence of experiences or advise at least 1 year ahead of patient recruitment. 

Including pharmacies is especially important if a pragmatic trial is run pre-licensing. Awareness needs to be raised and pharmacies need to be on board to ensure proper distribution of the drug that mimics a real life setting. Pharmacies can also support recruitment into pragmatic studies.

At the time of protocol writing continous alignment is needed to ensure feasibility. Prior to study exectuion participating pharmacies need to undergo training. Throughout the study ongoing feedback from participating pharmacies so no further alignment on top of that needed.

When idea for trial comes up.

The engagement of thought leaders in the respective country from the beginning ensures an independent view on the protocol, methodology, feasibility and external surrounding.

Continous consultation throughout the planning and execution phase.

Depending on the country and study: ~ 1 year ahead of patient recruitment, latest when feasibility study is run.

Groups that are overseeing the primary care and allocate money. As a pragmatic trial is usually performed (also) in a research naive setting,  the by-in of these groups is  needed, as it includes numerous important GPs that can advocate the idea of the study.

In advance of site feasibiliy as they can support idenficiation of new sites and support buy-in. Then as needed as the study progresses - they would appreciate regular updates on progress.

Depending on the country and study: ~ 1 year ahead of patient recruitment, latest when feasibility study is run.

This group is consisting of the ones that are doing the actual work on-site. They need to be on board to:
a) advise on feasibility at a site level
b) advocate the study 

As above, to improve site engagement, but also on-going if they are particpating in the study as they can help improve processes, for example. 

Depending on the country and study: ~ 1 year ahead of patient recruitment, latest when feasibility study is run

They can support the site recruitment by advocating the study within their practices. They need to be informed and feedback needs to be considered to ensure dedication by sites.

As above, to improve site engagement, but also on-going if they are particpating in the study as they can help improve processes, for example.