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The phrase "a significant difference when it comes" is correct and usable in written English.
You can use it to highlight a notable distinction in a specific context or subject matter.
Example: "There is a significant difference when it comes to the effectiveness of various teaching methods."
Alternatives: "a notable difference regarding" or "a considerable difference in terms of".
Exact(1)
There was however a significant difference when it comes to the source of treatment chosen (p < 0.01).
Similar(59)
The findings of these studies revealed no significant difference when it comes to the impact of reading elaborated and unmodified content on L2 vocabulary acquisition, and between reading elaborated and simplified texts.
These algorithms have significant differences when it comes to their sampling strategy.
There are also significant differences when it comes to women and what level of education they have attained.
This makes a huge difference when it comes to concentration.
Milliseconds make a difference when it comes to chat.
The difference, when it comes to compensation, can be significant: One of the widows, Mrs. Herbert Jones, rejected the benefit, sued the state and was awarded $1 million for her husband's death.
Why the difference when it comes to expert testimony?
Oscar noticed a significant difference when he morphed into Oscar.
These differences can be significant, particularly when it comes to the nature of public health practice.
Such differences in income are very significant when it comes to predicting academic performance.
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Since I tried Ludwig back in 2017, I have been constantly using it in both editing and translation. Ever since, I suggest it to my translators at ProSciEditing.

Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com