There have also been methodological drawbacks in the studies that have examined the volume-effectiveness relationship, and several suggestions for methodological improvements have recently been pointed out [ 11- 13].
16 A review 17 examining trials of LA in a range of orthopaedic diseases was equivocal, but noted methodological drawbacks in the studies included.
In fact, beneficial effects of bone-acting drugs in OA are increasingly reported, but reliable conclusions regarding their efficacy are hindered by methodological drawbacks in study design [ 10].
However, it should be noted that methodological drawbacks in the design and reporting of PROs have often limited the use of PRO data in approval of drugs [ 7].
The aim of this review is to analyze the major methodological drawbacks in mouse models of depression with a focus on its principal feature, anhedonia, in a chronic stress paradigm, and to share with the reader several procedural modifications resulting from our own experiences with a chronic stress model in C57BL/6N mice.
Finally, we are aware of methodological drawbacks in using BiSSE models when the taxonomic coverage is not exhaustive or below 300 terminals ([ 83], see [ 84] for a discussion on model inadequacy), so further examination of these trends with other methods is necessary.
We acknowledge this methodological drawback and undertook manual searches and contacted recognized experts in pediatric endocrinology.
The methodological drawbacks of studies on diets in CKD are similar to those of dialysis: randomization of peritoneal dialysis versus haemodialysis is considered 'unethical and unpractical'.
In cancer RCTs methodological drawbacks have often hampered a critical appraisal of results [ 9, 10].
Previous studies of sexual dysfunction in women with diabetes are small in number and have significant methodological drawbacks, including small sample sizes and lack of adequate characterization of diabetes, particularly with regard to glycemic control, neurovascular complications, psychological adjustment to diabetes, and presence or absence of comorbid depression (6).
