Trial informed consent forms,the Declaration of Helsinki and the SPIRIT 2025 statement

The revised SPIRIT 2025 statement “encompasses and builds on recommendations” from both the Good Clinical Practice E6(R3) guidance and the 2024 Declaration of Helsinki (DoH). ¹ Good Clinical Practice guidelines are primarily intended for trials of investigational products intended to be submitted to regulatory authorities. However, the DoH principles should be applied to all types of trials conducted in medical research. ² When reviewing SPIRIT 2025 from the research ethics perspective, two omissions are of concern.

First, the 2025 revision deleted an appendix – included in the 2013 original version – on “informed consent materials,” without providing any explanation.^1,3 SPIRIT was conceived as a guideline “for the minimum content of a clinical trial protocol” for all trials worldwide. ⁴ In this sense, it was considered appropriate to include the “model consent form.” ⁴ Since the SPIRIT checklist will be used by many investigators to learn the items that ought to be included in the protocol, a reminder of the need to include an informed consent form seems crucial.

This deletion is even more surprising since 2013, two regulatory changes have happened: (a) all US federally funded trials must post informed consent forms on a publicly available federal website (e.g. ClinicalTrials.gov) ⁵ and (b) all drug trials conducted in the European Union (EU) must post informed consent forms on the EU Clinical Trials Information System. ⁶ Deleting an appendix on the informed consent form ignores recent US and EU regulations.

Second, there is no mention of the need for all trials to comply with the DoH principles. Although the declaration has always been directed toward human research conducted by physicians, the 2024 revision states for the first time that DoH “principles should be upheld by all individuals, teams, and organizations involved in medical research.” ² Why did SPIRIT 2025 not include an item that reminds many non-medical researchers conducting medical research of their obligation to follow the latest DoH tenets?

This omission is worrisome since non-medical investigators (e.g. psychologists, nutritionists, sport science specialists, neuroscientists) conducting trials on non-regulated interventions may not have been trained to comply with DoH principles. A recent systematic review of 499 registered, non-pharmacological trials conducted in Spain and published in 2009–2024 revealed that 67% of them claimed to have followed the principles of the DoH. ⁷ Most of these trials were conducted by research teams that included physicians among their members. Yet, 38% of trials were authored by non-medical research teams. ⁷ This highlights the need for all healthcare professionals conducting medical research to be aware of their duty to conduct their trials in accordance with the DoH, especially in countries where regulations are limited to drug and device trials. ⁸

SPIRIT plays a critical didactic role among clinical trial investigators. SPIRIT authors should consider issuing an amendment to include an appendix concerning the informed consent form and an item on the need to follow the DoH tenets. This will also remind members of research ethics committees and institutional review boards of the need for all trials, regardless of the interventions evaluated and the background of the healthcare professionals involved, to comply with the principles of the DoH.