3 ms·

So, we know people get Dengue fever and what it does to people. Why do you still need the placebo group in a study like this? I'm having a hard time seeing th

So, we know people get Dengue fever and what it does to people. Why do you still need the placebo group in a study like this? I'm having a hard time seeing the morality of such a choice when we already have plenty of data on Dengue fever.

bobbles 11y ago
"The purpose of the placebo group is to account for the placebo effect, that is, effects from treatment that do not depend on the treatment itself" https://en.wikipedia.org/wiki/Placebo-controlled_study https://en.wikipedia.org/wiki/Placebo-controlled_study
- protomyth 11y ago
  Yeah, I know the purpose, but I'm really still having a tough time seeing any actual justification when we know how bad a diseases is. I cannot think of a reason it is worth it. I worked in clinical trials briefly (9 months) and still think its a level of cruel that borders on inhuman. "I'm sorry, we know the disease / condition kills, but we gave your loved one sugar pills".
  - ekianjo 11y ago
    The dengue fever does not kill most of the time. It makes you paralyzed with high fever for one to two weeks, but usually it does not kill you, unless you are already old and weak. I'm pretty sure that the recruitment for the clinical trial can ensure that only healthy people with appropriate constitution would not die from dengue fever.
    - protomyth 11y ago
      Don't we actually have enough data on the dengue fever to tell exactly what will happen to the control group? I don't think this is an actual unknown anymore.
      - ghshephard 11y ago
        So - what would you conclude if both the control group and the vaccine group didn't contract dengue during the trial?
      - ekianjo 11y ago
        Again, it is probably known - You would need to ask an expert, but I wage there are probably good reasons for having a control group, that we may not be aware of. I think the ethical question you raised is a serious concern in any clinical trial, so I would be very surprised if it is not addressed at any point by the trials's sponsors.
  - wbl 11y ago
    "I'm sorry, we gave your loved one a treatment that's actually harmful, because we didn't compare to the right group".
    - protomyth 11y ago
      They were doing a study and were going to give it out. I just don't believe that we don't already have the dataset of the control group.
  - pak 11y ago
    For this trial, the placebo and treatment groups are both composed of healthy volunteers that are exposed to a controlled amount of an attenuated dengue virus (called rDEN2Δ30). All groups in the trial are told the risks of exposure to the virus. Because the virus is attenuated (weakened), the risk of severe sickness is very very low. The point of using an attenuated virus is that this is a "challenge model" that is supposed to simulate an exposure to the real virus closely enough that one can judge if the vaccine is likely working, without exposing the patients to the risks of infection by the full-strength virus. CNN did a much better job than Wired in explaining this. http://www.cnn.com/2016/03/16/health/dengue-vaccine-effective/index.html http://www.cnn.com/2016/03/16/health/dengue-vaccine-effectiv... Therefore, the fact that the placebo group had certain levels of various symptoms (according to the article, 80% had a rash, 20% had nausea, etc.) is still important data for other scientists who are trying to judge if they should use the rDEN2Δ30 challenge model in their candidate vaccine trials. It's not intended to provide data on what natural dengue fever is like, which I agree would be unethical and unnecessary.
- ekianjo 11y ago
  Placebo controlled groups are not used for Cancer treatments, though. So it's not an universal rule.
  - refurb 11y ago
    That's because there are current treatments that can act as the control arm. In a cancer trial you'd typically compare standard of care with the new drug.
    - ekianjo 11y ago
      No, there is also an ethical concern behind it. We already know the survival rate per months for most cancers so there is no need to have a placebo group anyway. For cancer patients on trial we only want to offer a potential upside (once the drug is confirmed to be safe for use). Plus, there are some cancers out there with very few working treatments (so no real SoC) - If SoC is not available you would not consider a placebo group anyway.
      - refurb 11y ago
        Can you give some examples of trials where there wasn't a control arm (e.g. placebo or SOC)? I agree actual placebos are rare since there is always something you can give to a cancer patient, even if it doesn't work well. What I haven't seen is a clinical trial without a control arm. In terms of the ethical considers it's not unusual to run a trial for a yeat and then switch every patient over to the new drug.
ekianjo 11y ago
That's a valid point - I don't now enough about the dengue virus, but one possibility is that some folks are naturally immunized for the dengue fever, and if that is the case you would need to have a baseline to ensure that the vaccination works beyond that level/ratio. Just a guess.
ghshephard 11y ago
First, and most importantly, the variant of Dengue that they infected the (presumably somewhat healthy) person with was a weaker variant that is highly unlikely to do serious harm, particularly in a hospital environment. Second, I know you probably know this, but the purpose of the placebo/control group is to understand if the vaccine is actually doing anything, or whether there is another common factor (possibly placebo effect, but possibly environmental, diet, poorly activated dengue virus, etc...) that is preventing Dengue from taking hold. I.E. if you have two groups one with the Vaccine, and one with just the Placebo, and both are injected with the dengue virus, and the group with the Vaccine and the group with the placebo both don't contract Dengue - then you have to consider the strong possibility that the vaccine didn't help, but some other factor prevented the two groups from getting dengue. And, it's far, far better that you try this with 10 people, with a relatively weaker version of Dengue, in a controlled hospital environment where the person can be taken care of, in an area where they are very likely to get the more dangerous dengue regardless of the study, than to come to the incorrect conclusion that you have a workable Vaccine, that you then spend many more hundreds of thousands (millions?) of dollars in broader clinical trials - only to discover the vaccine wasn't really doing anything in the first place.

bobbles 11y ago

"The purpose of the placebo group is to account for the placebo effect, that is, effects from treatment that do not depend on the treatment itself" https://en.wikipedia.org/wiki/Placebo-controlled_study https://en.wikipedia.org/wiki/Placebo-controlled_study

protomyth 11y ago
Yeah, I know the purpose, but I'm really still having a tough time seeing any actual justification when we know how bad a diseases is. I cannot think of a reason it is worth it. I worked in clinical trials briefly (9 months) and still think its a level of cruel that borders on inhuman. "I'm sorry, we know the disease / condition kills, but we gave your loved one sugar pills".
- ekianjo 11y ago
  The dengue fever does not kill most of the time. It makes you paralyzed with high fever for one to two weeks, but usually it does not kill you, unless you are already old and weak. I'm pretty sure that the recruitment for the clinical trial can ensure that only healthy people with appropriate constitution would not die from dengue fever.
  - protomyth 11y ago
    Don't we actually have enough data on the dengue fever to tell exactly what will happen to the control group? I don't think this is an actual unknown anymore.
    - ghshephard 11y ago
      So - what would you conclude if both the control group and the vaccine group didn't contract dengue during the trial?
    - ekianjo 11y ago
      Again, it is probably known - You would need to ask an expert, but I wage there are probably good reasons for having a control group, that we may not be aware of. I think the ethical question you raised is a serious concern in any clinical trial, so I would be very surprised if it is not addressed at any point by the trials's sponsors.
- wbl 11y ago
  "I'm sorry, we gave your loved one a treatment that's actually harmful, because we didn't compare to the right group".
  - protomyth 11y ago
    They were doing a study and were going to give it out. I just don't believe that we don't already have the dataset of the control group.
- pak 11y ago
  For this trial, the placebo and treatment groups are both composed of healthy volunteers that are exposed to a controlled amount of an attenuated dengue virus (called rDEN2Δ30). All groups in the trial are told the risks of exposure to the virus. Because the virus is attenuated (weakened), the risk of severe sickness is very very low. The point of using an attenuated virus is that this is a "challenge model" that is supposed to simulate an exposure to the real virus closely enough that one can judge if the vaccine is likely working, without exposing the patients to the risks of infection by the full-strength virus. CNN did a much better job than Wired in explaining this. http://www.cnn.com/2016/03/16/health/dengue-vaccine-effective/index.html http://www.cnn.com/2016/03/16/health/dengue-vaccine-effectiv... Therefore, the fact that the placebo group had certain levels of various symptoms (according to the article, 80% had a rash, 20% had nausea, etc.) is still important data for other scientists who are trying to judge if they should use the rDEN2Δ30 challenge model in their candidate vaccine trials. It's not intended to provide data on what natural dengue fever is like, which I agree would be unethical and unnecessary.
ekianjo 11y ago
Placebo controlled groups are not used for Cancer treatments, though. So it's not an universal rule.
- refurb 11y ago
  That's because there are current treatments that can act as the control arm. In a cancer trial you'd typically compare standard of care with the new drug.
  - ekianjo 11y ago
    No, there is also an ethical concern behind it. We already know the survival rate per months for most cancers so there is no need to have a placebo group anyway. For cancer patients on trial we only want to offer a potential upside (once the drug is confirmed to be safe for use). Plus, there are some cancers out there with very few working treatments (so no real SoC) - If SoC is not available you would not consider a placebo group anyway.
    - refurb 11y ago
      Can you give some examples of trials where there wasn't a control arm (e.g. placebo or SOC)? I agree actual placebos are rare since there is always something you can give to a cancer patient, even if it doesn't work well. What I haven't seen is a clinical trial without a control arm. In terms of the ethical considers it's not unusual to run a trial for a yeat and then switch every patient over to the new drug.

ekianjo 11y ago

That's a valid point - I don't now enough about the dengue virus, but one possibility is that some folks are naturally immunized for the dengue fever, and if that is the case you would need to have a baseline to ensure that the vaccination works beyond that level/ratio. Just a guess.

ghshephard 11y ago

First, and most importantly, the variant of Dengue that they infected the (presumably somewhat healthy) person with was a weaker variant that is highly unlikely to do serious harm, particularly in a hospital environment. Second, I know you probably know this, but the purpose of the placebo/control group is to understand if the vaccine is actually doing anything, or whether there is another common factor (possibly placebo effect, but possibly environmental, diet, poorly activated dengue virus, etc...) that is preventing Dengue from taking hold. I.E. if you have two groups one with the Vaccine, and one with just the Placebo, and both are injected with the dengue virus, and the group with the Vaccine and the group with the placebo both don't contract Dengue - then you have to consider the strong possibility that the vaccine didn't help, but some other factor prevented the two groups from getting dengue. And, it's far, far better that you try this with 10 people, with a relatively weaker version of Dengue, in a controlled hospital environment where the person can be taken care of, in an area where they are very likely to get the more dangerous dengue regardless of the study, than to come to the incorrect conclusion that you have a workable Vaccine, that you then spend many more hundreds of thousands (millions?) of dollars in broader clinical trials - only to discover the vaccine wasn't really doing anything in the first place.