results in the observational studies (e.g. that the wrong type of adjustment had been used or the timing of initiating treatment mattered),119,120 but these were eventually refuted.121,122 Likewise, randomized trials have not confirmed the 30% increased risk of breast cancer found in observational studies of estrogen-alone preparations, although the results for combined estrogen-progestin preparations appear similar.123-125 Despite these discrepancies, the similarity of the direction but not – the size126,127 of the differences in the rates of stroke and pulmonary embolism – in observational studies and in randomized trials of hormone replacement therapy has been used to justify continued reliance on observational evidence,2 rather than as an illustration of the difficulty of determining which if any associations with – – treatment in observational studies provide a reliable basis for safe and effective care of patients and the public. A number of reviews have been conducted to compare the estimates of treatment effects from observational studies and randomized trials, but their methods have been criticized (chiefly because of concerns about the methods used to select the studies and compare the results) and their findings have been inconsistent.106 It has been concluded that these reviews identified many examples where the results of the same intervention were on average the same, but also many examples where the results differed. For example, there have been many claims about the benefits of various vitamin supplements based on observational studies128,129 that have been reliably refuted by large-scale randomized trials.130-132 Similarly, when compared with the results from randomized trials of the effects of treatments for several different cancers, observational studies have generated improbable results despite controlling for comorbidity, extent of disease and many other characteristics that were recorded in detailed databases133-135 (as is also the case for reported
results in the observational studies (e.g. that the wrong type of adjustment had been used or the timing of initiating treatment mattered),119,120 but these were eventually refuted.121,122 Likewise, randomized trials have not confirmed the 30% increased risk of breast cancer found in observational studies of estrogen-alone preparations, although the results for combined estrogen-progestin preparations appear similar.123-125 Despite these discrepancies, the similarity of the direction – but not the size126,127 – of the differences in the rates of stroke and pulmonary embolism in observational studies and in randomized trials of hormone replacement therapy has been used to justify continued reliance on observational evidence,2 rather than as an illustration of the difficulty of determining which – if any – associations with treatment in observational studies provide a reliable basis for safe and effective care of patients and the public. A number of reviews have been conducted to compare the estimates of treatment effects from observational studies and randomized trials, but their methods have been criticized (chiefly because of concerns about the methods used to select the studies and compare the results) and their findings have been inconsistent.106 It has been concluded that these reviews identified many examples where the results of the same intervention were on average the same, but also many examples where the results differed. For example, there have been many claims about the benefits of various vitamin supplements based on observational studies128,129 that have been reliably refuted by large-scale randomized trials.130-132 Similarly, when compared with the results from randomized trials of the effects of treatments for several different cancers, observational studies have generated improbable results despite controlling for comorbidity, extent of disease and many other characteristics that were recorded in detailed databases133-135 (as is also the case for reported
Revised%20paper%20on%20statin%20evidence%20interpretation_110716_CLEAN%2c%20Collins%20et%20al.docx