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Research Methods & Reporting

SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials

BMJ 2013; 346 doi: (Published 09 January 2013) Cite this as: BMJ 2013;346:e7586

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Re: SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials

In your guidance you are presenting an example schedule requiring a written informed consent as the second-earliest action.
A global guideline should respect their US rule that the “prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence” [1]. While the WMA Declaration of Helsinki does not have a similar rule [2], regional physicians’ organisations have similar rules, namely to give the patient (at least for diagnostic or surgical interventions) sufficient time for consideration [3]. Also ICH GCP [4] calls for “ample time and opportunity ... to decide whether or not to participate in the trial” (§ 4.8.4) and prohibits to “coerce or unduly influence a subject to participate ...” (§ 4.8.3).
Because of these rules as well as general considerations I have difficulties in understanding why a written consent on participation in a randomised clinical trial should be obtained just during an initial visit. In fact, many patients (and maybe physicians) would refuse such coercion. I think that patients insisting on time for consideration are the reason for many violations in the dates when consent was in fact obtained [4]. Auditors and inspectors will criticise “wrong” dates as violation of the protocol. But why should the protocol always require written consent at that point?
So, please explain how to come to a written informed consent at the initial visit without coercion or undue influence?
Closely related to this concern is the rule expressed elsewhere in your guideline that “patients ... must provide written informed consent before any study procedures occur”. While I am unable to identify any guideline requiring such rule (although I know that this is “tradition”), I am aware of an FDA guidance on screening informed consents [6] that provide principles for having only a verbal consent for simple procedures at that time point. Would such verbal consent not be more realistic in many situations? And provide the patient indeed ample time to consider participation based on the written patient information until randomisation? Note that patient information sheets tend to comprise 10 to 20 pages nowadays.
So why should it be an imperative to get a written informed consent just during the initial visit?
I would recommend rethinking the procedures for obtaining informed consents. Maybe in the past too much emphasis was given on formalisms (“any study procedures”, data protection) rather than on the manifest risks of the participation in randomised research, namely the risks to get a possibly inferior (e.g. placebo) or a potentially harmful (active) treatment. I would prefer getting truly informed patients who participate on the own free will rather than (too) rapidly signed forms that might be followed by lack of compliance.

1. USA CFR - Code of Federal Regulations Title 21, Part 50, Protection of Human Subjects. Subpart B, 20: Informed Consent of Human subjects.
2. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects, amended by the 59nd WMA General Assembly, Seoul 2008.
3. Berufsordnung Landesärztekammer Baden-Württemberg. Status Dezember 2012
4. ICH E6: Guideline for Good Clinical Practice (Step 4: May 1996, step 5 (EU: CPMP/ICH/135/95: Note for Guidance on Good Clinical Practice)
5. Shapley SL. The most common findings in clinical trials inspections – an FDA perspective. 2009.
6. US FDA: Screening Tests Prior to Study Enrollment - Information Sheet Guidance for Institutional Review Boards and Clinical Investigators.

Competing interests: No competing interests

02 February 2013
Hans-Joachim Kremer
Medical Writer
Medical Writing Service
Alemannenstraße 101, 79117 Freiburg, Germany