FEM
Depends on the respective problem, your formulation, algorithm used, precision of desired results and optimization issues, if any.
In weak formulation fourth order will be second order then solution should be C-01 continuous. What are the difficulties for C-01 continuity.
No big problems !
Just one thing, instead of Lagrange Elements, you have to use Hermite finite elements which guaranty the $C^1$ condition !
Otherwise, you may use mixed formulation and then you don’t need to satisfy this differentiability condition.
Can you explain mixed formulation?
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Harmonic differential quadrature method
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While solving any BV problem using this methods.
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