4 ms·

it took a little searching, but I found one for an alternative manufacturing process of the measles vaccine. https://clinicaltrials.gov/ct2/show/NCT01536405?te

by viggity 10y ago

it took a little searching, but I found one for an alternative manufacturing process of the measles vaccine. https://clinicaltrials.gov/ct2/show/NCT01536405?term=AMP&rank=12 https://clinicaltrials.gov/ct2/show/NCT01536405?term=AMP&ran...

nonbel 10y ago
Thanks, it looks like this one was done after I was searching. This study doesn't really have the outcomes we need to measure though. There is no placebo group, they didn't check for measles diagnoses (by doctors who didn't know whether they were vaccinated), and they only measured antibody levels for 1.5 months after 1 vaccine dose in children 12-23 months old (ie before going to school when exposure usually occurs). Unfortunately, I really don't think this study offers us anything about whether "vaccines work". You can see that the main concern is whether doctors are much more likely to diagnose measles when they do not believe a vaccination occurred, and whether introduction of the lab tests made the diagnostic definition more stringent: “This was not a blind study, since the investigators knew which children had received measles vaccine. It seems probable that the occurrence of so much ‘measles-like’ illness in the vaccinated children was a reflexion of the difficulty in making a firm diagnosis of measles in the African child at one visit.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2134550/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2134550/ “A likely reason for this is that the case may have been misdiagnosed as a non-specific viral illness. Measles has become relatively uncommon in Singapore with two decades of widespread measles vaccination, and especially after the second dose policy was implemented in 1998. Many primary care doctors may not even see a single case of measles in a year. This makes diagnosis more difficult. [...] As only approximately 7% of the clinically-diagnosed cases of measles reported locally turned out to be measles by laboratory testing, there is a need for laboratory confirmation of measles to avoid misidentification of cases and improve disease surveillance.(2)” http://www.ncbi.nlm.nih.gov/pubmed/17609829 http://www.ncbi.nlm.nih.gov/pubmed/17609829
nonbel 10y ago
Here is another one, apparently we can get a drop of up to 99.5% just by switching to lab tests from clinical diagnosis: "Indeed, an average of only 100 cases of measles are confirmed annually [32], despite the fact that >20,000 tests are conducted [28], directly suggesting the low predictive value of clinical suspicion alone." http://jid.oxfordjournals.org/content/189/Supplement_1/S185.full http://jid.oxfordjournals.org/content/189/Supplement_1/S185.... I just don't think these alternative explanations have been investigated very well, and the blinded RCT (vs placebo) is missing. Another thing, the various proxies for "vaccine success" they use do not correlate with each other... "Our data demonstrate that regression analysis shows only limited correlation between NT results and the ELISA values. This is in agreement with other reports [4]. Similar limitations in the correlation were also reported for other viruses like Cytomegalovirus (CMV) [10]. In case of the gamma globulin samples, the low correlation might reflect the wider spectrum and heterogeneity of the involved or measured measles antibodies." http://www.ncbi.nlm.nih.gov/pubmed/17308917 http://www.ncbi.nlm.nih.gov/pubmed/17308917
- mattkrause 10y ago
  That's not a sensible interpretation of that measles data. Since measles is very contagious, there's a lot of effort putting into identifying and isolating cases. This necessarily involves screening many cases where the disease is only weakly suspected. On top of that, the current protocols cast a really wide drag net. Australia, for example, tests every susceptible patient who shared a waiting room with a measles patient, as well as those who entered less than two hours after the index case left. In a busy hospital or practice, this could be a lot of children. Thus, the high ratio of tested to confirmed cases doesn't mean doctors are bad at diagnosing measles; they may just be cautious.
  - nonbel 10y ago
    So how large do you think such a diagnosis effect may be? That other paper reported only 7% of clinical diagnoses were lab positive for measles in Singapore. And yet another effect to deal with is that people used to spread measles on purpose: “Before the introduction of measles vaccines, measles virus infected 95%–98% of children by age 18 years [1–4], and measles was considered an inevitable rite of passage. Exposure was often actively sought for children in early school years because of the greater severity of measles in adults.” http://jid.oxfordjournals.org/content/189/Supplement_1/S4.full http://jid.oxfordjournals.org/content/189/Supplement_1/S4.fu... I think for these reasons it is clear the effectiveness of measles vaccines has been overstated, it is only a matter of how much.

by viggity 10y ago

nonbel 10y ago

Thanks, it looks like this one was done after I was searching. This study doesn't really have the outcomes we need to measure though. There is no placebo group, they didn't check for measles diagnoses (by doctors who didn't know whether they were vaccinated), and they only measured antibody levels for 1.5 months after 1 vaccine dose in children 12-23 months old (ie before going to school when exposure usually occurs). Unfortunately, I really don't think this study offers us anything about whether "vaccines work". You can see that the main concern is whether doctors are much more likely to diagnose measles when they do not believe a vaccination occurred, and whether introduction of the lab tests made the diagnostic definition more stringent: “This was not a blind study, since the investigators knew which children had received measles vaccine. It seems probable that the occurrence of so much ‘measles-like’ illness in the vaccinated children was a reflexion of the difficulty in making a firm diagnosis of measles in the African child at one visit.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2134550/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2134550/ “A likely reason for this is that the case may have been misdiagnosed as a non-specific viral illness. Measles has become relatively uncommon in Singapore with two decades of widespread measles vaccination, and especially after the second dose policy was implemented in 1998. Many primary care doctors may not even see a single case of measles in a year. This makes diagnosis more difficult. [...] As only approximately 7% of the clinically-diagnosed cases of measles reported locally turned out to be measles by laboratory testing, there is a need for laboratory confirmation of measles to avoid misidentification of cases and improve disease surveillance.(2)” http://www.ncbi.nlm.nih.gov/pubmed/17609829 http://www.ncbi.nlm.nih.gov/pubmed/17609829

nonbel 10y ago

Here is another one, apparently we can get a drop of up to 99.5% just by switching to lab tests from clinical diagnosis: "Indeed, an average of only 100 cases of measles are confirmed annually [32], despite the fact that >20,000 tests are conducted [28], directly suggesting the low predictive value of clinical suspicion alone." http://jid.oxfordjournals.org/content/189/Supplement_1/S185.full http://jid.oxfordjournals.org/content/189/Supplement_1/S185.... I just don't think these alternative explanations have been investigated very well, and the blinded RCT (vs placebo) is missing. Another thing, the various proxies for "vaccine success" they use do not correlate with each other... "Our data demonstrate that regression analysis shows only limited correlation between NT results and the ELISA values. This is in agreement with other reports [4]. Similar limitations in the correlation were also reported for other viruses like Cytomegalovirus (CMV) [10]. In case of the gamma globulin samples, the low correlation might reflect the wider spectrum and heterogeneity of the involved or measured measles antibodies." http://www.ncbi.nlm.nih.gov/pubmed/17308917 http://www.ncbi.nlm.nih.gov/pubmed/17308917

mattkrause 10y ago
That's not a sensible interpretation of that measles data. Since measles is very contagious, there's a lot of effort putting into identifying and isolating cases. This necessarily involves screening many cases where the disease is only weakly suspected. On top of that, the current protocols cast a really wide drag net. Australia, for example, tests every susceptible patient who shared a waiting room with a measles patient, as well as those who entered less than two hours after the index case left. In a busy hospital or practice, this could be a lot of children. Thus, the high ratio of tested to confirmed cases doesn't mean doctors are bad at diagnosing measles; they may just be cautious.
- nonbel 10y ago
  So how large do you think such a diagnosis effect may be? That other paper reported only 7% of clinical diagnoses were lab positive for measles in Singapore. And yet another effect to deal with is that people used to spread measles on purpose: “Before the introduction of measles vaccines, measles virus infected 95%–98% of children by age 18 years [1–4], and measles was considered an inevitable rite of passage. Exposure was often actively sought for children in early school years because of the greater severity of measles in adults.” http://jid.oxfordjournals.org/content/189/Supplement_1/S4.full http://jid.oxfordjournals.org/content/189/Supplement_1/S4.fu... I think for these reasons it is clear the effectiveness of measles vaccines has been overstated, it is only a matter of how much.