Patient input into the protocol
Patient input enters a clinical trial protocol as a question asked at the start of design, about who the participants are and what they need, and the protocol records the decisions that input shaped.
Why protocols are expected to include patient input
Patient centricity means treating patients as active partners rather than passive participants. The shift towards it is still in its infancy, although it is now part of all the key guidance. ICH E8(R1) and E6(R3) codify it, and patient engagement should be done as far as possible. The World Health Organization's best practice for clinical trials holds that potential participants and members of the relevant community provide valuable contributions to the design, execution and interpretation of the results of clinical trials. The biggest change in the SPIRIT 2025 statement, which revises the protocol items of the 2013 statement, concerns patient and public involvement and how protocols should mention it. The TransCelerate common protocol template, and templates derived from it, have included it for a number of years. Patient and public involvement and engagement has become an essential part of clinical trial development.
There is a demand, and a need, for patient engagement to improve trial performance. Trials struggle both to enrol participants and to keep them from dropping out, for example of overly complex protocols. Patient engagement overlaps with work on diversity, equity and inclusion, with decentralised trials and with regulations and guidance. Although the guidelines say that trials should be more patient-centric and the need is great, not all study teams recognise that need yet.
What patients weigh in a trial
In a choice experiment on what motivates people to take part in a trial, respondents separated into two groups. One group was influenced by the trial's design features, such as how long the visits are, how many there are and what the trial changes in daily life, and the other looked at the treatment, such as its dosing regimen, its safety and anything else about the product. So a product with a better dosing regimen than its comparators does not on its own make everyone want to join, since the trial also has to fit into the participants' lives. A participant asked to go to a study site two hours away asks who will take care of their commitments.
Ergonomic design of clinical trials is increasing, and regulators, clinical researchers and participants all support it. Exactly how it is incorporated, and at what cost in money and in development time, is still decided case by case.
Asking for patient input at the start of design
A protocol conversation that begins with the product and what the trial will do comes to patient input at section 4 of the TransCelerate template, which asks whether there was any patient input into the design. The writer can instead reframe the opening question away from the product and the design, such as what the product's indication is and what trial design will be used, towards who the target population is and what its preferences and needs are. Setting an expectation of some patient input at least makes clear that such input is now expected, as best practice says, and writers should help teams understand that it is relevant. Expecting the input by default changes the question from whether there will be any patient input into the design to when it is expected, so that the timelines can be planned accordingly. A team that has done no patient engagement and plans none will say so, and the expectation will not change that, but it has at least been presented as the position.
The supplementary research behind a protocol is often built from the product material: which sites, what will be done, and telephone visits where a visit is not enough to warrant going to a site. Reframed, it asks what can be reduced in order to increase technical success, meaning enrolment that is as fast as possible and participants who stay in the trial until its end. The aim is to tailor the trial as far as possible to its participants and to its sites.
To persuade investigators to include patient engagement in protocol design, the writer should at least ask about it. Where the subsection on patient input into trial design in section 4 of the common protocol template is a standard part of the protocol, the study team has to be asked what it has done. A team that chooses not to seek input will ultimately have to demonstrate to the investigators, the regulatory bodies and the ethics committees that the choice is justified. Raising awareness helps, and so does citing the ICH guidelines, and regional guidelines or guidance from national bodies are also very influential.
What a patient advocate can answer about a protocol
Patient advocates can define the endpoints and outcomes that are relevant to patients. They can inform the study design, for example by flagging where crossover in a treatment arm should be allowed and at what point. They can flag whether the sponsor is targeting the wrong population, which benefits and risks are the most important to measure, and whether the proposed inclusion and exclusion criteria will inadvertently exclude an important subgroup. They can also flag whether too invasive or too many procedures will discourage enrolment, increase the dropout rate or make full adherence difficult. They can give input on measures of adherence, and especially on quality of life. And they can review the synopsis and the protocol amendments for readability by patients.
Recording patient input in the protocol
In the protocol, the writer can make clear that patient input into the document is an expected part of the trial design. The trial team should expect it, because most protocol templates are based on the TransCelerate Common Protocol Template and include a subsection on patient input into the trial design. ICH E8(R1) and E6(R3) also highlight the need for a quality-by-design approach, in which quality factors are built into the scientific and operational design of the trial so that it meets its objectives, and patient input into the trial design is a fundamental part of that approach.
In line with that approach, the writer can ensure that patient input is included transparently in the protocol. The writer supports this by asking targeted questions while developing the trial documents and by ensuring that the insights are communicated throughout the trial lifecycle and its documents. What the protocol records can be reused or repurposed at later stages of the trial. Detailed and accurate reporting of patient and public involvement and engagement helps increase its visibility and promote its adoption by the clinical research community.
For each protocol element, the patient input that bears on it and what the writer should consider are:
| Protocol element | Patient input | Medical writer considerations |
|---|---|---|
| Trial objectives and endpoints | Unmet needs, disease burden, important endpoints | Clearly articulate patient-identified unmet needs and how trial objectives address them. Explain how objectives or endpoints that are important to patients have been incorporated. |
| Trial design | Concerns about travel, invasive procedures, technical support needs | Describe what patient input has been achieved and how the trial design accommodates patient preferences (e.g., decentralised visits, minimised invasive procedures). Explain any patient support systems in place. |
| Eligibility and participation | Representation, support during screening, withdrawal process | Highlight how eligibility criteria have been modified to encourage diverse representation. Clearly describe the informed consent process, including withdrawal procedures. |
| Trial drug | Administration concerns, expectations about side effects | Explain how patient concerns about drug administration are addressed. Clearly communicate expected side effects and their management. |
| Patient-reported outcomes (PROs) | Relevance, complexity, administration of PROs | Describe how PROs were selected or modified based on patient input. Explain measures taken to ensure PRO accessibility and ease of completion. |
| Trial results | How and when patients will receive results | Clearly state in the protocol how and when trial results will be communicated to participants. |
What involvement changed in a spinal muscular atrophy programme
Spinal muscular atrophy (SMA) is a genetic disease that affects the central nervous system, the peripheral nervous system and voluntary muscle movement. In a collaboration between Roche, PTC Therapeutics and the SMA Foundation that began in 2011, patients, caregivers and advocates were involved at every stage of the clinical development programme, from discovery through clinical trial planning and design to submissions to health authorities and access to treatment. The SMA Foundation, SMA Europe and Cure SMA helped set research priorities, gave input on draft study protocols and reviewed informed consent forms, assessment schedules and family guidance for self-administration. Their feedback led to broader inclusion criteria, less restrictive exclusion criteria, reduced trial burden on patients and families, and the seamless integration of the phase 2 and phase 3 trials into a single uninterrupted study conducted in two parts. The importance patients and caregivers placed on maintaining independence in everyday life led to the co-development of a novel SMA independence scale.