Atul Gawande has made human lapses more understandable, if not acceptable, reminding us that "We miss stuff. We are inconsistent and unreliable because of the complexity of care," and making the idea of checklists mainstream, rather than a prop for failing memories.
One of the difficulties for any new researcher—and some experienced ones—is designing a protocol that is sound and practical. Because of the great variability in the quality of protocols—and thus the value of the data gathered—an international group developed the SPIRIT statement, a primer on developing a protocol. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) initiative began in 2007; their main publication recommendations were issued earlier this year.
The international group developing this model included clinical trial investigators and coordinators, journal editors, research ethicists, methodologists, statisticians, and regulators. Their strategy consisted of a Delphi consensus survey, systematic reviews of existing protocol guidelines, and consensus meetings.
The resulting product from standardization of protocols will eliminate the possibility of careless oversights and force attention to details of protocols before they are implemented. There is a 33 point checklist that includes many standard items, such as a descriptive title and acronym for the study, and a protocol version number. Item 2 promotes registration of the clinical trial, which will encourage transparency and discourage selective reporting of positive results.
Other items, however, are often not explicitly addressed and are welcome additions. For example,
5c: “Role of study sponsor and funders…in writing of the report; and the decision to submit the report for publication, including whether they will have ultimate authority over any of these activities.”
The rationale, 6a, should provide the “justification for undertaking the trial, including summary of relevant studies (published and unpublished) examining benefits and harms for each intervention.” Wouldn’t that be nice!
Similarly, 6b calls for an “Explanation for choice of comparators.” I wonder if anyone would admit to choosing a suboptimal dose for the comparator, in order to make their product look more successful, or if this format would discourage such shenanigans. There are too many studies done for marketing advantage rather than for truly furthering science, putting patients at unnecessary and unethical risk.
The protocol items go on to include standard sections of methods, participant selection (inclusion-exclusion criteria), study intervention, and outcomes assessment. But each of these, the group assignments and data analysis, are made more explicit, with explanations provided ahead of time explaining the rationale for each choice.
I am particularly happy to see additional patient protections:
26b "Additional consent provisions for collection and use of participant data and biological specimens in ancillary studies, if applicable"
27 "How personal information about potential and enrolled participants will be collected, shared, and maintained in order to protect confidentiality before, during, and after the trial
30 "Provisions, if any, for ancillary and post-trial care, and for compensation to those who suffer harm from trial participation"
For the protection of investigators, item 29 calls for an upfront statement as to who will have access to the trial data and whether agreements limit an investigator’s access. Authorship is also clearly delineated.
Further general background on protocols can be found at Clinical Trials for Beginners: Recipe for a new drug. Details of the SPIRIT13 can be found at:
SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials
SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials
and at the SPIRIT website, which also includes their checklist.
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