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That’s the spirit – how to avoid the most common mistakes in study protocol
In medicine, authors should follow the EQUATOR Network-Guidelines to ensure that at least all essential information for the respective study type is available in the manuscript. The “Standard Protocol Items: Recommendations for Interventional Trials” (SPIRIT)-Statement is the internationally recognized standard for protocols of clinical studies. The 33 items on the SPIRIT-checklist cover topics from administrative information to methodical and ethical aspects. However, a publication by the “Trials”-journal has revealed that in 2019, only 57% out of 150 submitted study protocols adequately addressed all SPIRIT-checklist’s points. Why is that?
The authors of the aforementioned publication are SPIRIT protocol editors who examine and verify the SPIRIT-conformity of submitted protocols. After 2 years of experience and approximately 1900 reviews of 1100 study protocols, they summarized the most common protocol faults and named their pet peeves. As a first step, each author listed independently the 12 SPIRIT items that they have to correct the most, in their opinion. Then they aligned on a final list containing all items with double or triple mentions. So, let us walk the walk of shame together and look more closely at 5 interesting items. You can find a full listing here.
SPIRIT item 14: “Estimated number of participants needed to achieve study objectives and how it was determined, including clinical and statistical assumptions supporting any sample size calculations.”
Generally, most protocols indicate the key data for this item, i.e., the sample size, the level of significance, the statistical power and the underlying assumptions. Nevertheless, additional information is often missing, such as the software used, type of hypothesis tests, references, or if the sample size already takes into account a loss to follow-up. Authors should justify missing information for the sample size. If you want to check if your protocol delivers all relevant information on this item, ask yourself: “Is the information in the protocol sufficient for an uninvolved third party to (roughly) reproduce the estimated parameters?”
SPIRIT item 21b: “Description of any interim analyses and stopping guidelines, including who will have access to these interim results and make the final decision to terminate the trial.”
Who carries out the interim analyses? How will it be decided whether a study will be continued or terminated? Authors should check if their protocol addresses these questions and if the termination criteria are clearly defined. Authors should also consider whether a study will be stopped if the effectiveness of the intervention is so high that it would be unethical to withhold it from the placebo group.
SPIRIT item 25: “Plans for communicating important protocol modifications (e.g., changes to eligibility criteria, outcomes, analyses) to relevant parties (e.g., investigators, REC/IRBs, trial participants, trial registries, journals, regulators).”
Many protocols state “not applicable” on this item. However, the reviewers clarify that this point always applies – ultimately, nobody can predict the course of studies. Authors should also assure that all relevant instances are informed about protocol modifications according to protocol: many protocols do not mention investigators, which is somewhat embarrassing, especially in large-scale multicenter studies.
SPIRIT item 26b: “Additional consent provisions for collection and use of participant data and biological specimens in ancillary studies, if applicable.”
Many authors seem to overlook that point 26b concerns biological samples as well as data collected during the study that may be used in follow-up studies. The reviewers give 2 recommendations: First, if no biological samples are collected, authors should preferably write: “This trial does not involve collecting biological specimens for storage” instead of “not applicable.” Second, authors should state if they use the collected data for further studies and if they gathered the patients’ consent for it.
SPIRIT item 31c: “Plans, if any, for granting public access to the full protocol, participant-level dataset and statistical code.”
This is another point where protocols often state “not applicable” even though this is never correct. The reviewers speculate that some authors only think of the protocol’s release here, but of course they should state whether the study data will be made public or not.
Other annoyances for editors in clinical study protocols
Besides from the SPIRIT checklist, the publication provides further tips authors of clinical study protocols should pay attention to. A sample of 90 protocols points out that 14% of submissions provide no version number and date. Even such trivial aspects as incorrect page references or missing page numbers belong to the reviewers’ pet peeves. Furthermore, the reviewers recommend the use of professional editing and translation services, as the quality of the English language is often substandard.
Conclusion
The publication by Qureshi et al. is a must-read for authors of clinical study protocols. The numerous hints and recommendations could be decisive to tip the balance from “perish” to “publish.”
Source
Qureshi R, Gough A and Loudon K. The SPIRIT Checklist-lessons from the experience of SPIRIT protocol editors. Trials 2022; 23(1): 359.