It is so exciting to see new CDKL5 research publications announced. But finding access to scientific journal articles, understanding the studies they describe and interpreting the results can be challenging. Sorting out the studies’ goals, size, and type is enough to make one’s head spin. We should understand how bias was minimized, identify potential conflicts of interest, and understand how the conclusions stack up to similar studies. And also, if it is statistically or clinically meaningful information.
Who has time for all of that?
Research ought to be made contextually available to the patient community so we can better gauge what it means and what the next steps to move it forward are. IFCR has committed to sharing our thoughts on CDD research. Our goal is to help you understand the strengths and weaknesses of the published work. We will also discuss what still needs to happen for the study to translate to actual human interventions when appropriate.
For now, we hope this resource will be a helpful guide as you skim any “hot off the press” CDD studies.
What is a preprint?
A preprint is an early version of a scientific manuscript posted on a public platform that has not yet been subjected to peer review. It is a case when scientists choose to share experimental results early to receive input from other investigators that they can incorporate into their final publication. In the rare disease community, preprints can accelerate the speed at which science moves forward.
Preprints as “workable manuscripts” are citable with their own unique DOI, thus, part of the scientific record. To view a recent example of a preprint funded by IFCR, click here. The availability of preprints is a fantastic resource for the patient and the scientific community. Still, we need to understand it comes with limitations. Not unlike conference presentations of new scientific findings, results are subject to change following peer review.
What is peer review and why do it?
The process of peer review involves a team of reviewers (or referees) selected by the journal editor for their expertise in the area of research reviewed. Several reviewers receive a submitted paper from the editor and provide individual critiques, which may not all be in agreement. The editor then makes the final decision on whether the paper will be declined for acceptance or what changes need to be made if it is to be accepted. Areas that reviewers comment on when critiquing a manuscript include:
- The quality of the science: Do errors exist in data analysis or the methods used?
- The significance or overall impact of the manuscript’s findings.
- How novel is the work, and will it advance the field?
- Finally, reviewers recommend the paper is rejected or accepted (this may include the contingency “with minor or major changes”).
Peer review can be likened to a quality-control system. When a team of reviewers approves a paper for publication, they are essentially stating that the science described has met community standards and is deemed valid.
Reproducibility and Validation
Concerns have been raised as to how effective the peer review process really is in detecting errors in academic papers. Reviewers don’t have access to the raw data on which facts in a paper are based. If a scientist knowingly falsifies data or if a scientist makes an understandably human mistake, reviewers may not be able to detect it.
A second quality-control mechanism is the ability of other scientists to duplicate or validate the results of published research beyond peer review. No single research paper can be considered the final word, and science moves faster by corroboration, that is when researchers verify others’ results. This is an essential step when interpreting the clinical relevance of and, hopefully, translating preclinical rodent studies to clinical application.
Other Helpful Resources
“I DON’T KNOW WHAT TO BELIEVE…”
Making Sense of Science Stories: This guide is for people who follow debates about science and medicine in the news. It explains how scientists present and judge research and the questions you can ask when presented with scientific and medical information.
Know the Science
9 Questions To Help You Make Sense of Health Research: Here are 9 questions that can help you make sense of a scientific research article.
Same Research Institution, Same Mouse Model, Different Results
Last, we need to look no further than CDKL5 studies to find examples of contradictory research conclusions. Below is a linked commentary discussing different results found in work using the IFCR funded R59X mouse model. It relates to two research studies at the University of Pennsylvania conducted in the Jensen and Zhou labs, published in different journals. Is it AMPA? Or is it NMDA? In the end, both studies, although at odds, are important steps forward in CDD research.
Here is the commentary publication, Reigning in Excitatory Signaling in CDKL5 Deficiency, that discusses contradictory results of synaptic alterations caused by CDKL5 gene mutations.
“… Two recent studies from the University of Pennsylvania have addressed these questions and come to slightly different conclusions.”
Here are links to the studies discussed in the commentary:
AMPA Receptor Dysregulation and Therapeutic Interventions in a Mouse Model of CDKL5 Deficiency Disorder
Yennawar M, White RS, Jensen FE. J Neurosci. 2019;39(24):4814-4828.
Altered NMDAR Signaling Underlies Autistic-Like Features in Mouse Models of CDKL5 Deficiency Disorder
Tang S, Terzic B, Wang IJ, et al. Nat Commun. 2019;10(1):2655.