Scoping a regulatory document and running its kickoff
Much of what decides whether a regulatory document can be delivered is settled before it is drafted: what the deliverable actually is, what the timeline is agreed against, what a kickoff meeting has to fix, how the document's dates are held against the documents on either side of it, and how study deliverables are planned where they vary by modality.
Scoping the deliverable
Preparation is one of the important steps in developing a protocol, and writers can benefit from preparing thoroughly. One experienced regulatory writer counts determining the real scope of projects among the challenges of the job: people often say the scope will be small, and often it is not.
What scoping settles
Understanding the scope is the most important task to do before setting timelines and before the kickoff meeting. It starts from the basics, such as the phase, the indication and the product, and extends to what will happen while the protocol is developed and at its final stage. The items that typically need to be defined when starting on a protocol are the following, and other aspects may matter in the context of a particular writer's work:
- Gather the available material: the trial outline or synopsis, the investigator's brochure, the clinical development plan or target product profile, and anything that illustrates the quality indicators for the trial.
- Establish the target geography, because where the study is conducted affects the content. Most templates now already include EU-CTR content, for example, and there can be other regional differences.
- Identify the template and the style guide.
- Define the process: not only who contributes, but who signs off and who approves, involving them as early as possible so that late-stage reviewers do not add more comments.
- Identify the technology the team will use during development.
- Establish the target completion date, what is driving that date and whether it can move if challenges emerge, and the standard operating procedures.
- Anticipate the external influences on the protocol's execution.
- Identify the key risks to the deliverable's success.
Focusing the team on what is critical to quality can help make clear at the beginning what is needed and what is wanted, so that the team focuses first on the critical elements, the needs, and then on the wants.
Teams are starting to use many tools, such as AI software, that influence the protocol. Unlike team members, with whom there is open dialogue and whose progress can be seen, these tools can cause an abrupt shift in the content of the protocol. Understanding where a tool comes in, what it will be involved with and what it could change in the protocol therefore helps as well.
External influences on the protocol's execution, such as emerging data, patient input and regulatory input, are becoming more apparent, and there are also external committees and external reviews. Teams are not always purely in-house: external individuals such as key opinion leaders and consultants are becoming more apparent in them, especially in smaller organisations. Helping the team focus on the risks to the deliverable's success during development has become more significant for writers, because the risks can be numerous and a writer will not necessarily know at the beginning what they mean, so they need attention throughout.
One agency writer suggests asking the team for examples of similar, recently finished documents, and does so regularly, because each client has preferences that templates and style guides alone may not make clear; the examples help keep documents from the same client consistent and show what the client expects.
Drafts and the events that add to them
The scope of a protocol usually assumes a set number of drafts and a final, such as two drafts and a final, though organisations can differ, and that assumption does not always hold. In one worked example, planned events break it: a study design the team expects to change during the review of draft one, emerging data drawn in during development, which is becoming more commonplace, an organisational management review by senior leadership, typically independent of the team working on the protocol, and regulatory or patient feedback expected after that review. In that example the management review added reviewers, and new reviewers bring new changes, so the protocol could not go straight to final and another draft had to come first. A path that includes several extra reviews cannot fit within the original timeframe, so the writer has to be upfront and realistic with the team about the implications of what they plan.
When scoping is skipped
A protocol that is not scoped successfully is likely to lead to team dissatisfaction and potentially to failure. If progress towards completion stalls, the protocol can end in a stalemate of endless rounds of review, and the more reviews and revisions it goes through, the more likely discrepancies are to be introduced. The trial itself can also bloat in what it collects, which affects how it performs.
Teams generally want to move as quickly as possible: they have cleared several hurdles to reach this stage, they want to move forward on their critical path, they have many other things to do, and they want the first participant in within a defined period connected to milestones. They have a lot riding on the protocol, and however much the writer wants time to understand it, the writer has to help them reach what they want to do. Understanding the team's critical path for a few steps ahead, though not the whole way through, can help the writer appreciate the process the team has to follow and where the writer can support it in bringing the protocol to completion.
The kickoff meeting
Creating a regulatory document often follows a standard process of kickoff meeting, drafting, review and quality control of the final draft. A writer's interaction with clients and teams differs depending on the employer or on whether the writer is self-employed, and it helps to understand how that dynamic will be set; the kickoff of the project is the starting point, where expectations can be set.
What the kickoff is for
A kickoff matters most at the beginning of a project, when the team decides who is responsible for which content and agrees on timelines and other project details. Many writers advocate meeting face to face, which in a multinational company will often not be possible, and a video conference or a conference call with screen sharing can then be the next best thing. The meeting also generally sets the tone and gives the writer a feel for the team dynamic, for who will be cooperative and who problematic.
The complexity of studies is increasing. Teams have more members, a number that grows every year, with increasingly diverse expertise. The scope is larger, and most clinical trials are now multi-country; even within one country a trial may be multi-site, so the protocol has to reconcile different perspectives and be fit for all of them. Good planning, a good summary and a team focused in the same direction help deliver the protocol within the timeframe.
Who leads it
Teams cannot be assumed to know the writer's role or how the process works, so a well-structured kickoff at the start of every document puts the whole team on the same page and sets clear expectations. One writer holds that the lead writer should lead every kickoff for their document. In that writer's experience, joining a team only after its kickoff left the writer unable to establish themselves as process lead or even as an equal team member. Leading the kickoff lets the writer introduce themselves as process leader and main contact for questions, concerns or updates that may affect the document, and a well-planned and well-led meeting makes the team feel safe and trust the writer to lead them. Writers not yet experienced in leading one may ask a senior colleague to let them attend one of the colleague's kickoffs and see how the colleague leads the discussion and establishes a working relationship from the very start.
Preparing for it
Leading a kickoff is a bit of a black art, and writers may prefer different approaches, but one experienced writer believes it is important to prepare conscientiously. The writer should have read the background information and be familiar with the project, because nothing is more annoying for a busy person than attending a meeting and thinking they are wasting their time.
Meeting key stakeholders before the wider kickoff is particularly effective, to get earlier commitment and direction. With procedural questions such as which template to use and who signs off settled in advance, the kickoff can be presented to the wider team more formally, as what the team is going to do. Timelines in particular are a known pain point for teams, so a pre-read with someone from the team gets early buy-in, which means the timelines are at least plausible and that, if the timelines are challenged, there is some support for them.
The preparation can run in this order: meet the project leader, or whoever assigned the protocol, to understand the background of the study and their thoughts on when the kickoff should be, who should be invited, and what the target completion date is and why; complete the scoping task; set the kickoff date; meet the client and the project leader to confirm the kickoff details; then review the final slides and the risk assessment.
What it covers
A strong kickoff is crucial because it sets the parameters, and four key topics to include in it are the target patient population, the overall objectives of the study, the priorities among them, and the timelines and key risks.
The target population matters for any study that does not enrol healthy volunteers, who are a kind of professional participant population. With ICH E6(R3) and, by extension, E8(R1), a patient-focused protocol needs to start with the key demographic, who the study is looking to enrol. The team can also be asked whether any outreach was done before protocol development; sometimes clients or team members hold patient advisory group discussions about the product. Anything that informs the writer and the team as they start work helps make the protocol more patient-centric.
Setting priorities means asking what is critical and what is nice to have. The primary objective and its related activities are critical, key secondary objectives are critical, and exploratory objectives are often not critical but nice to have, though there can be surprises among them.
It is very important to focus the team on where a writer who has worked on such deliverables before sees the biggest risks. Bringing the team to an understanding of the risks, so that they can help and can understand the writer's perspective and position, makes things easier. Each risk is either mitigated with a solution or accepted and dealt with when the time comes. Regulatory input expected halfway through development, which could lead to significant changes, cannot be mitigated, because the feedback cannot be stopped, but there can be contingencies: one path if the changes are minimal and another if they are more substantial. Preparing the team in this way helps ensure that everyone understands and is not surprised.
One regulatory writer's tips for the kickoff are to get the team to agree on goals and the timeline, to give the reasons for tight deadlines, and to ask the team to respect everyone's time and not delay the process.
A kickoff agenda can cover the following topics:
- Background: Provide background information so that everyone has a clear understanding of the project and its scientific and regulatory environment.
- Team: Identify all team members by line function, including the lead writer and any supporting writers, and include all line functions the standard operating procedure requires. Clearly identify authors, reviewers, viewers, approvers and other tasks, for example in separate tables for each task. Give the team time to check the list for mistakes, missing personnel or potential delegates.
- Process: Give an overview of the process under the standard operating procedure. Clarify the roles of the lead writer, any supporting writers, and the other authors and contributors, reviewers and approvers. Clarify how the document will be drafted, reviewed, approved and published, including any specific software and document management platforms, if applicable. Establish a communication plan with preferred communication methods and, if needed, regular catch-up calls.
- Timelines: Include all tasks the standard operating procedure requires, including drafting, review and approval periods, slots for important meetings such as comment resolution meetings after each draft review, and publishing steps, if applicable. The team should confirm its agreement with the proposed timeline and its availability when needed, and delegates should be assigned for absences to ensure each line function stays involved.
After the kickoff
The writer should follow up after the kickoff with a summary of what was discussed and where the priorities lie, because team members are not necessarily experienced with kickoff meetings: someone assigned to a study might attend one to three of them every two years. The follow-up includes placeholders for the reviews and for the comment resolution meetings (CRMs), and the responsibilities, including who will find out the answer to anything still unclear.
It is important to communicate continuously after the kickoff, so that the project goes as planned and everyone is up to speed with any shifts in scope and timelines, because the plan can sometimes deviate. The writer should prepare and circulate the meeting minutes so that everyone, including non-attendees, stays on the same page.
Aligning timelines with neighbouring documents
Regulatory documents can depend on each other, and a document that informs another, or one that another informs, may be written by another writer with their own timelines. An investigator's brochure that must describe data from a clinical study report needs its writer to align with that report's writer on when the information is coming, and a protocol's writer may have another writer preparing the informed consent form downstream. It is important that writers of interdependent documents communicate and know each other's timelines so that the documents are on time, and where the timelines overlap, they need to align closely so that no time is lost and all of them can be met.
Playbooks for deliverables that vary by modality
Biotherapeutics exist as many modalities, such as antibodies, antibody–drug conjugates, peptides and oligonucleotides, and the studies needed to support first-in-human investigational new drug applications and, ultimately, marketing authorisation vary with the modality. That diversity is a challenge for a regulatory writer who supports biotherapeutics programmes and manages study components and submission contributions. One response, created by a pharmaceutical company's nonclinical pharmacokinetic and ADME group, is a generic playbook that defines the group's study deliverables at key drug development milestones for each modality, and so gives its writers basic information to help them plan study components for regulatory submissions.
Because each programme is unique, and the timing and the specific studies conducted vary with many factors, the same group was, in 2012, taking the generic playbook a step further with a historical playbook based on the company's own portfolio, maintained as a reference and archival system that captures what was learned in an evolving field. The group shared its approach to breaking down a complicated process for training, guidance and reference, to guide similar efforts by regulatory writers in any drug development discipline, such as drug safety and clinical pharmacology.