A recent perspective article in the journal Alzheimer’s & Dementia, postulates that current Alzheimer’s drug trials do not yet provide convincing evidence that the treatments actually slow or change the underlying course of the disease. The authors suggest that, while these drugs have shown modest benefits in slowing cognitive decline over about 18 months, recent evidence from extension studies and sub-analyses call into question their disease modifying role. True disease-modifying treatments, they posit, should continue to provide a lasting benefit by changing the underlying disease process.
The authors synthesise recent reports and operationalise the data to demonstrate that proof of disease modification requires stronger clinical trial designs than those used so far. They recommend, amongst other things, a longer and more roust "delayed-start" trial (where one group starts treatment earlier than another). In this trial design, if the early-treatment group continues to do better even after the delayed group catches up on treatment, this would suggest disease alteration. They also stress that studies should clearly state their hypotheses in advance, report complete numerical results, and carefully account for patients who leave the study, as these factors can otherwise make treatments appear more effective than they really are.
The authors argue that the long-term extension studies reporting results from recent trials, do not meet these higher standards due to problems in a number of factors like randomisation and comparison groups. They conclude that these studies remain valuable for assessing long-term safety, but clinicians practicing in the real-world clinical setting should exercise interpretational caution until stronger evidence becomes available.
More information on this study is available here: https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.71643
