3 ms·

"One piece of evidence that preregistration can act as a strong corrective comes from clinicaltrials.gov, a registry of publicly and privately funded clinical s

"One piece of evidence that preregistration can act as a strong corrective comes from clinicaltrials.gov, a registry of publicly and privately funded clinical studies involving human subjects. Before 2000, when the site was established, 57 percent of large clinical trials funded by the National Heart, Lung and Blood Institute showed a significant benefit of drugs or other intervention, according to a recent analysis published in the journal PLOS One. After the registry was put in place, only 2 percent of such trials found a clear benefit."

jMyles 11y ago
I think it's healthy to suspect that the entire pharmacopoeia-industrial-complex has a similar rate of veracity.
- ArekDymalski 11y ago
  I'm absolutely sure about that. As a student I was working (as a technician) on many medical science conferences, so I had an opportunity to see the "bleeding edge" research presentations. I was shocked by the level of confidence demonstrated by "scientists" who promoted results of their N=5 experiments (without a comparison group) as "convincing". If all therapies are based on such research, we have to be happy that our bodies are impressively self-repairing machines.
var_eps 11y ago
I'd recommend Irving Kirsch's __Emperor's new drugs: Exploring the antidepressant myth__ as an accessible introduction to this topic. The book goes beyond statistics and draws attention to "clinical significance" that is crucial to keep in mind when evaluating drugs. Statistical significance helps to inform whether a metric has changed; clinical significance tells whether it actually mattered from a patient's perspective.
- keithflower 11y ago
  Dr. Kirsch's (a psychologist) work has been valuable, with some justified criticisms of antidepressant therapy and their trials. But his work did not show that antidepressants are clinically ineffective. Dr. Kirsch's analysis showed that for mild depression treated with antidepressants, there is in fact an improvement in symptoms of depression based on rating scales like the Hamilton Depression Scale - but for mild depression, this improvement in the numbers doesn't necessarily translate into what you correctly identify as clinical significance. However, Dr. Kirsch's own "cutoff" for whether or not such a numerical increase constitutes "clinical significance" or not is itself just an arbitrary number that itself has been criticized. Also, Kirsch's own metaanalyses (and other metaanalyses) show clearly that for moderate and severe depression (and other conditions), antidepressants are indeed clinically effective (in other words, yes, the benefits actually "mattered" from a patient's perspective), and, importantly, they are highly effective at preventing relapse. They work, and work well. In addition, there are a variety of reasons why many short-term clinical trials of antidepressants (which have made up the bulk of clinical trials of SSRIs, for example) are entirely different from the way physicians prescribe antidepressants (and other medications) clinically, and may underestimate their benefit even for cases of mild depression. The beneficial effects of antidepressants increase with longer exposure (i.e. exceeding the length of a six week clinical drug study), probably because of downstream neurotrophic factor(s) increases. Many trials of antidepressants limited dose adjustment or dose adjustment rate. Many clinical trials have excluded patients with severe symptoms or dual diagnoses because inclusion introduces a safety issue or may introduce too many variables. Also, physicians will switch patients to another antidepressant if there is no sign of early efficacy, and while one antidepressant may work very well (probably as a result of genetics), another will not work at all. Most studies focusing on one drug are not going to switch to another medication in the same class (for example, a serotonin reuptake inhibitor) during the trial, even though that's routinely done in clinical practice with good result. Antidepressants work. Psychotherapy can also be helpful as a sole treatment for mild depression (although please note that psychotherapy has its own set of risks, costs, and drawbacks), and patients often get additional benefit by engaging in psychotherapy along with medication treatment. However, a psychologist or counselor treating a moderately to severely depressed person who fails to refer that patient for evaluation for treatment with an antidepressant would be risking a malpractice suit.

jMyles 11y ago

I think it's healthy to suspect that the entire pharmacopoeia-industrial-complex has a similar rate of veracity.

ArekDymalski 11y ago
I'm absolutely sure about that. As a student I was working (as a technician) on many medical science conferences, so I had an opportunity to see the "bleeding edge" research presentations. I was shocked by the level of confidence demonstrated by "scientists" who promoted results of their N=5 experiments (without a comparison group) as "convincing". If all therapies are based on such research, we have to be happy that our bodies are impressively self-repairing machines.

var_eps 11y ago

I'd recommend Irving Kirsch's __Emperor's new drugs: Exploring the antidepressant myth__ as an accessible introduction to this topic. The book goes beyond statistics and draws attention to "clinical significance" that is crucial to keep in mind when evaluating drugs. Statistical significance helps to inform whether a metric has changed; clinical significance tells whether it actually mattered from a patient's perspective.

keithflower 11y ago
Dr. Kirsch's (a psychologist) work has been valuable, with some justified criticisms of antidepressant therapy and their trials. But his work did not show that antidepressants are clinically ineffective. Dr. Kirsch's analysis showed that for mild depression treated with antidepressants, there is in fact an improvement in symptoms of depression based on rating scales like the Hamilton Depression Scale - but for mild depression, this improvement in the numbers doesn't necessarily translate into what you correctly identify as clinical significance. However, Dr. Kirsch's own "cutoff" for whether or not such a numerical increase constitutes "clinical significance" or not is itself just an arbitrary number that itself has been criticized. Also, Kirsch's own metaanalyses (and other metaanalyses) show clearly that for moderate and severe depression (and other conditions), antidepressants are indeed clinically effective (in other words, yes, the benefits actually "mattered" from a patient's perspective), and, importantly, they are highly effective at preventing relapse. They work, and work well. In addition, there are a variety of reasons why many short-term clinical trials of antidepressants (which have made up the bulk of clinical trials of SSRIs, for example) are entirely different from the way physicians prescribe antidepressants (and other medications) clinically, and may underestimate their benefit even for cases of mild depression. The beneficial effects of antidepressants increase with longer exposure (i.e. exceeding the length of a six week clinical drug study), probably because of downstream neurotrophic factor(s) increases. Many trials of antidepressants limited dose adjustment or dose adjustment rate. Many clinical trials have excluded patients with severe symptoms or dual diagnoses because inclusion introduces a safety issue or may introduce too many variables. Also, physicians will switch patients to another antidepressant if there is no sign of early efficacy, and while one antidepressant may work very well (probably as a result of genetics), another will not work at all. Most studies focusing on one drug are not going to switch to another medication in the same class (for example, a serotonin reuptake inhibitor) during the trial, even though that's routinely done in clinical practice with good result. Antidepressants work. Psychotherapy can also be helpful as a sole treatment for mild depression (although please note that psychotherapy has its own set of risks, costs, and drawbacks), and patients often get additional benefit by engaging in psychotherapy along with medication treatment. However, a psychologist or counselor treating a moderately to severely depressed person who fails to refer that patient for evaluation for treatment with an antidepressant would be risking a malpractice suit.