Pharmaceutical industry urges ICH to expand E22 guideline to cover caregiver input

The International Council on Harmonization (ICH) E22 guideline should incorporate caregiver feedback, according to responses submitted by industry groups and manufacturers to a US Food and Drug Administration (FDA) public consultation.

Caregiver feedback is particularly important in cases where patients are too young to provide their own input or are incapacitated and unable to do so, the commenters noted.

In addition, both the Biotechnology Innovation Organization (BIO) and the Pharmaceutical Research and Manufacturers of America (PhRMA) proposed including definitions for terms such as patient experience data (PED), patient-reported outcomes (PRO), and clinical outcome assessments (COAs).

The ICH E22, released in November 2025, includes harmonized considerations regarding the use, design, analysis, and submission of (PPS) to inform drug development. The guidance recommends that the PPS should be included in modules 2 and 5 of the Common Technical Document (CTD) (RELATED: ICH announces new topics, adopts harmonized template for clinical trial protocols, Regulatory Focus 26 November 2025).

FDA released the guideline for public comment in February 2026. The deadline for public comment was 7 April 2026.

The guidance states that common uses of PPS include identifying treatment priorities; informing the selection of endpoints for subsequent clinical trials; and determining what constitutes a meaningful change of an endpoint.

Twelve interested parties commented on the guidance.

Respondents recommend inclusion of caregiver preference studies

BIO, PhRMA, and Thermo Fisher Scientific recommended expanding the guidance to include caregiver preference studies when patients cannot provide input.

“The current scope excludes caregiver preference studies, despite their critical importance in disease areas where patients are unable to directly provide preference information. While this is particularly relevant in pediatric populations, it also applies broadly to conditions involving cognitive impairment or diminished decision-making capacity (e.g., Alzheimer’s disease and other dementias, certain psychiatric or neurological disorders, and severe disabilities). In these contexts, caregivers (including parents and study partners) frequently act as appropriate proxies or agents of the patient, and their preferences may represent the most relevant and feasible source of input,” BIO wrote in their comments.

According to comments from PhRMA, “there are many therapeutic contexts in which patients may be unable to provide preference information, e.g., due to young age, psychiatric disorders, dementia, or disability. In these instances, common practice—and in some cases, the only option for measuring preference—is to assess the preferences of parents or other caregivers in their role as agents of the patient.”

Thermo Fisher Scientific said that “scoping caregiver preference studies out leads to a lack of guidance on undertaking preference studies to inform the relative desirability of treatments in these contexts, which is potentially inequitable. Suggest including a more nuanced discussion on this and including caregiver studies in scope when caregiver preferences are relevant to treatment decisions. We agree that caregiver preferences should not be used in lieu of patient preferences when the patient is able to make their own treatment decisions and it is feasible to elicit their preferences.”

BIO and PhRMA suggest harmonized definitions

BIO and PhRMA suggested including definitions for terms such as patient experience data (PED), patient-reported outcomes (PRO), and clinical outcome assessments (COAs), as well as a glossary at the end of the guideline.

BIO states that “as the first ICH guideline focused on patient preference studies within the broader patient experience data (PED) landscape, the absence of a harmonized PED definition may limit clarity and consistent interpretation. Additionally, the distinction between PPS and other PED types, particularly PROs and COA, is not clearly described, making it difficult to understand scope boundaries and exclusions.”

PhRMA concurred on the need for a definition of PED.  “Given that this is the first ICH guideline to discuss a specific type of patient experience data (PED), we suggest that FDA and ICH consider including a harmonized definition of PED, drawing from existing definitions provided by regulatory bodies and consortia.”

Not requiring PPS studies in certain situations supported

Two respondents indicated their support for the guidance provision, stating that PPS studies may not always be necessary.

The guidance states that “although most studies are designed for a specific set of attributes and therapeutic context, there may be existing relevant PPS literature that can address the intended research objective and question(s). Ongoing and future studies should take existing relevant literature of sufficient quality into consideration to avoid unnecessary burden on the patient community.” 

Faegre Drinker Consulting wrote that “the guideline appropriately acknowledges that de novo patient preference studies may not always be justified, particularly when high-quality evidence exists. This principle is important for several reasons: It helps reduce unnecessary burden on patients and caregivers who may already be frequently asked to participate in research. It discourages redundant studies that provide little incremental value. It supports efficient use of limited research resources, especially in rare disease contexts where patient populations are small.”

The Lupus Foundation concurred. “The guideline appropriately acknowledges that de novo patient preference studies may not always be justified, particularly when high-quality existing evidence is available.”

BIO says PPS should be in the labeling

BIO further suggested that PPO information should be included in product labeling where relevant to prescribing decisions.

BIO states that “declaring labeling placement 'outside the scope of this guideline' means PPS evidence may be submitted to regulators, but never reach prescribers or loop back to patients. An ICH harmonisation guideline should not leave the most clinically impactful destination for PPS data unaddressed.”

The group said, “the FDA has demonstrated through the rituximab SC approval …. that inclusion of PPS data in labeling is feasible in some cases. Given this precedent, the guideline should address that this is a possibility.”

According to Genentech, which co-developed the drug with IDEC Pharmaceuticals, FDA used extensive patient information from nearly 2,000 patients in approving Rituxan Hycela (subcutaneous rituximab)in 2027.

BIO also suggested that the guideline be more tailored to drug development and to differentiate between early drug development, late-stage development, and in the postmarketing realm.

“The guideline applies a broadly uniform standard without distinguishing between trial phases or development stages. This creates two risks in practice: sponsors may cite early-phase context to avoid PPS altogether, while regulators may apply the same expectations to Phase 1 safety studies as to late-stage confirmatory trials. Neither outcome serves patients or science. PPS is valuable and most feasible at specific points in development (e.g., endpoint selection, benefit-risk assessment ahead of Phase 3, post-marketing label updates), and the guideline should reflect this.”

Thermo Scientific suggests inclusion of vaccines

In its comments, Thermo Scientific suggested that the guideline clarify that vaccines are in scope.

“We assume vaccines are in scope and would suggest explicitly stating this in the footnote (as an example of a preventive medicinal product). PPS can generate structured insights about the relative importance of characteristics, also referred to as attributes, that are considered by patients when making decisions about drugs (or other medicinal products). Suggest stating vaccine as an example of a preventive medicinal treatment in the footnote.”

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