HIV Vaccine!

[Puppycow]

Combo vaccine reduces risk of HIV infection, researchers say

Unfortunately, it's only about one-third effective, but it's a start.

Quote:

(CNN) -- A vaccine to prevent HIV infection has shown modest results for the first time, researchers have found.

In what is being called the world's largest HIV vaccine trial ever, researchers found that people who received a series of inoculations of a prime vaccine and booster vaccine were 31 percent less likely to get HIV, compared with those on a placebo.

"Before this study, it was thought vaccine for HIV is not possible," Col. Jerome Kim, who is the HIV vaccines product manager for the U.S. Army, told CNN.

Kim emphasized that the level of efficacy was modest, but given the failures of previous HIV vaccine trials, "yesterday we would have thought an HIV vaccine wasn't possible."

He called the results from the trial an important first step that will help researchers work toward a more effective vaccine.
. . .
"These results show that development of a safe and effective preventive HIV vaccine is possible," said Col. Nelson Michael, who is director of the U.S. military HIV research program.

[Kahalachan]

How are experiments like these carried out?

It's unethical to inject people with HIV.

[fls]

Originally Posted by Kahalachan

How are experiments like these carried out?

It's unethical to inject people with HIV.

You find a population which is already at higher risk for HIV acquisition - a rule of thumb is that you need to expect at least 50 cases in your control group.

Linda

[Lothian]

Originally Posted by Kahalachan

How are experiments like these carried out?

It's unethical to inject people with HIV.

The article suggests that no one was injected with HIV!

This study showed that 9 per 1000 people on the placebo got HIV compared to 6.5 per 1000 on the drug. 16,000 took part but only 125 caught HIV. I am no expert but wonder about the confidence level when so few went on to get the disease. There are no details in the article as to how many of each group were in high HIV risk categories.
While any improvement in preventing HIV is welcome we need to be sure that this drug does have the supposed effect.

[Darat]

Originally Posted by Puppycow

Combo vaccine reduces risk of HIV infection, researchers say

Unfortunately, it's only about one-third effective, but it's a start.

It is good news - just bad that it had to come out of socialist research (sorry I couldn't help myself).

[fls]

Originally Posted by Lothian

The article suggests that no one was injected with HIV!

This study showed that 9 per 1000 people on the placebo got HIV compared to 6.5 per 1000 on the drug. 16,000 took part but only 125 caught HIV. I am no expert but wonder about the confidence level when so few went on to get the disease. There are no details in the article as to how many of each group were in high HIV risk categories.

This would only matter if you had reason to believe that the group given placebo contained more people at high risk. Randomization should distribute the people who are in high HIV risk categories evenly between the groups. Alternatively, even if the distribution is uneven it is just as likely to be the vaccine group who is at higher risk than it is to be the placebo group (i.e. the vaccine works much better than indicated).

Linda

[fls]

Originally Posted by Darat

It is good news - just bad that it had to come out of socialist research (sorry I couldn't help myself).

I don't think this is the sort of research which Beerina is looking for. After all, it will preferentially affect morbidity and mortality in the disenfranchised and the poor. Those are not the deaths she/he has displayed concern about.

Linda

[Kahalachan]

Originally Posted by fls

You find a population which is already at higher risk for HIV acquisition - a rule of thumb is that you need to expect at least 50 cases in your control group.

Linda

Oh!!!!!!! Hah hah got it. Such a simple solution.

I should've figured this out.

[Lothian]

Originally Posted by fls

This would only matter if you had reason to believe that the group given placebo contained more people at high risk. Randomization should distribute the people who are in high HIV risk categories evenly between the groups.

It should, but there is a known link between high risk groups and getting the disease. Whether this treatment stops it is not known. The difference seems very low; 0.024% less chance of getting HIV in the treatment group. I wonder if it could be down to other factors than the treatment. I appreciate that there are limits to what can be done to ensure the two groups are similar and that with 16,000 starting this trial I can't really expect a bigger one. It is the confidence factor that I don't understand. Can we say as result of this that we are 100% certain that this treatment lowers the risk or a case where we are only 50% certain?

Quote:

Alternatively, even if the distribution is uneven it is just as likely to be the vaccine group who is at higher risk than it is to be the placebo group (i.e. the vaccine works much better than indicated).

Linda

Thanks. Never thought of that.

[Careyp74]

do the participants know what the trial was for? I think this could affect the outcome. Even more so than other trials, since HIV contraction relies highly on a person's actions. Sure, it has equal chance of affecting each group, but this would diminish the confidence level. I would expect that another trial with 100,000 would show no difference at all between inoculation and placebo.

[Jorghnassen]

Originally Posted by Lothian

Can we say as result of this that we are 100% certain that this treatment lowers the risk or a case where we are only 50% certain?

From simple stats, it appears to be the standard 95% confidence level. You never get 100%, and 50% is nowhere near statistical significance, thus studies with such "confidence" usually don't get published unless it's a large study that refutes previous studies that appeared more confident...

[Captain.Sassy]

Originally Posted by Careyp74

Sure, it has equal chance of affecting each group, but this would diminish the confidence level.

How so? If each group similarly engages in riskier behaviour, then the results of the experiment should still hold I think.

Also you could check to see if the participants in the experiment did actually engage in riskier behaviour by comparing infection rates in the placebo group to infection rates in the general population.

[McHrozni]

Originally Posted by Lothian

The article suggests that no one was injected with HIV!

This study showed that 9 per 1000 people on the placebo got HIV compared to 6.5 per 1000 on the drug. 16,000 took part but only 125 caught HIV. I am no expert but wonder about the confidence level when so few went on to get the disease. There are no details in the article as to how many of each group were in high HIV risk categories.
While any improvement in preventing HIV is welcome we need to be sure that this drug does have the supposed effect.

The study did say the difference could be due to chance. They will try to replicate the results now.

McHrozni

[Cuddles]

Originally Posted by Lothian

0.024% less chance of getting HIV in the treatment group.

No, 31% less chance of getting HIV.

Quote:

Can we say as result of this that we are 100% certain that this treatment lowers the risk

Of course not. A single un-replicated study can never give 100% certainty, even when the results are far more conclusive. But it's certainly a good sign.

[Segnosaur]

Originally Posted by Kahalachan

How are experiments like these carried out?

It's unethical to inject people with HIV.

They could use lawyers...

[Cuddles]

Originally Posted by Segnosaur

They could use lawyers...

It would be just as unethical to inject people with lawyers.

[Lothian]

Originally Posted by Cuddles

No, 31% less chance of getting HIV.

My choice of percentage was quite deliberate. I have just finished rereading Ben Goldacre’s ‘Bad science’ book. He suggests that comparative percentages can be misleading and it is far better to express them in terms of absolute risk.

Quote:

Of course not. A single un-replicated study can never give 100% certainty, even when the results are far more conclusive. But it's certainly a good sign.

Thanks, I realise that, and I realise that my 50% example was just as unrealistic. I was hoping someone would know how to work out the confidence from the numbers in the article.

[Lothian]

Originally Posted by Cuddles

It would be just as unethical to inject people with lawyers.

But injecting Lawyers with HIV is not so clear cut.

[volatile]

Might vaccination perhaps encourage risky sexual behaviour? Is there a "moral hazard" to rolling our this type of treatment, particularly as it's only 1/3rd effective?

[Jorghnassen]

Originally Posted by Cuddles

No, 31% less chance of getting HIV.



Of course not. A single un-replicated study can never give 100% certainty, even when the results are far more conclusive. But it's certainly a good sign.

No study, however replicated, can give 100% certainty.

[Lothian]

To expand on my comment above. Any Medical interventions can have a side effects and carry a risk. From the article some 7800 people were given 6 injections, that is nearly 47,000 injections. This appears to have prevented 19 people from developing HIV.

We do need to weigh up the benefits against the risk. Were this to stop a common cold, it would not be worth it. HIV is far more serious but the cost benefit analysis still needs to be done.

In respect of Ben Goldacre’s percentage point .

A treatment could give a relative 80% reduction in the chance of developing an illness.

If the chances of getting that disease are 1 in 2 then the treatment will reduce this to 1 in 10 and certainly looks worth it. The chance of getting the disease has dropped from 50% to 10% a 40% reduction in absolute terms.

If the chances of getting the disease are 1 in a million then a 80% reduction will make it 1 in 5 million. You have to go to a few decimal places of a single percentage before noticing a difference. In those circumstances people may chose to take their chances.

It is easier for people to decide by reviewing the absolute than the relative risks.

[Jorghnassen]

Originally Posted by Lothian

My choice of percentage was quite deliberate. I have just finished rereading Ben Goldacre’s ‘Bad science’ book. He suggests that comparative percentages can be misleading and it is far better to express them in terms of absolute risk.

Absolute risk is not particularly useful for comparing rare events with catastrophic consequences.

Quote:

Thanks, I realise that, and I realise that my 50% example was just as unrealistic. I was hoping someone would know how to work out the confidence from the numbers in the article.

Do your own damn p-value computation (I get 0.01945 or 98.05% "achieved" confidence).

[Careyp74]

Originally Posted by Captain.Sassy

How so? If each group similarly engages in riskier behaviour, then the results of the experiment should still hold I think.

Also you could check to see if the participants in the experiment did actually engage in riskier behaviour by comparing infection rates in the placebo group to infection rates in the general population.

That is true that you could check the placebos against the general population, but there is an expected difference there because of sampling, so it would be hard to tell if there is an effect from knowing you are in the study.

[whatthebutlersaw]

Will it be possible to design the attempts at replication using placebo? I mean ethically - are these results so small that there is not an ethical dilemma in giving placebo to participants?

Apropos the effect of participating in a study: I would have guessed that participating in a study could change the participants' behaviour so that they are less likely to engage in risk behaviour, just as easily as the other way around. To a lot of people the wish for their clinician to "look good" might be stronger than the "heck, I might be vaccinated, let's see if it worked" side of the coin.

The numbers are tauntingly small, but not small enough to be just brushed off. Since they are doing efficacy trials, I am assuming that safety and tolerability has already been ascertained, so it would be really interresting to see a huge study on this.

I am cautiously optimistic.

[Puppycow]

I expect further improvements in the future. Sure, 31% reduction in risk is not too impressive, but as a first step it's enormous. The first airplane was not very useful either, but you have to learn to crawl before you can walk.

[HansMustermann]

Originally Posted by Lothian

But injecting Lawyers with HIV is not so clear cut.

Good grief, man. Not so clear cut? Viruses can sometimes accidentally get a gene or two from a host too, and transfer them to the next host. It's one mechanism for horizontal gene transfer. Just the thought of using lawyers there gives me the creeps.

[Puppycow]

Originally Posted by whatthebutlersaw

Will it be possible to design the attempts at replication using placebo? I mean ethically - are these results so small that there is not an ethical dilemma in giving placebo to participants?

I think so. Tell everyone to assume that they are not protected and take reasonable protections. It's not worse than not participating in the trial at all.

[Careyp74]

Originally Posted by Cuddles

No, 31% less chance of getting HIV.

I don't like when stats are used like that. If the numbers were slightly different, say, 51/8000 and 102/8000 instead of 74, you could say you have a 100% greater chance of getting HIV without the treatment. That sounds drastic when it isn't at all.

Lothians way is more acceptable, to me at least, although the calculation is a little off I think, I got a difference of .2875%

[Careyp74]

Originally Posted by Puppycow

I think so. Tell everyone to assume that they are not protected and take reasonable protections. It's not worse than not participating in the trial at all.

That is the type of distortion I was talking about earlier. The study you are suggesting would give no usable data.

[shadron]

Originally Posted by Lothian

If the chances of getting the disease are 1 in a million then a 80% reduction will make it 1 in 5 million. You have to go to a few decimal places of a single percentage before noticing a difference. In those circumstances people may chose to take their chances.

That is true, but at least in the sample the chances of getting infected were somewhere in excess of 125/16000, or 1 in 128 (in the group for this study). A 30% reduction makes it 1 in 200. Obviously they aren't stopping there but want to do better, and now have encouraging signs. Your 80% means 1/640 or so. Still unwilling to take chances on that?

[Lothian]

Originally Posted by Careyp74

I don't like when stats are used like that. If the numbers were slightly different, say, 51/8000 and 102/8000 instead of 74, you could say you have a 100% greater chance of getting HIV without the treatment. That sounds drastic when it isn't at all.

Lothians way is more acceptable, to me at least, although the calculation is a little off I think, I got a difference of .2875%

I used 8200 placebo 7800 treatment.

Reading again

Quote:

The new study was conducted in Thailand, with more than 16,000 people between ages 18 and 30 participating. They were all HIV negative at the beginning of the trial.

Nearly 8,200 received a placebo and a similar number received a combination of six vaccines over six months. All were followed for three years.

perhaps it should be 8200 and 8200.

[Jorghnassen]

Originally Posted by Lothian

I used 8200 placebo 7800 treatment.

Reading again

perhaps it should be 8200 and 8200.

It's 8197 and 8198 to be exact

[Lothian]

Originally Posted by shadron

That is true, but at least in the sample the chances of getting infected were somewhere in excess of 125/16000, or 1 in 128 (in the group for this study). A 30% reduction makes it 1 in 200. Obviously they aren't stopping there but want to do better, and now have encouraging signs. Your 80% means 1/640 or so. Still unwilling to take chances on that?

80% was a hypothetical example. Here it appears to be about 1 in 110 (placebo) or 1 in 160 (treatment).

I think the true odds vary based on peoples lifestyle especially with STDs.

If it was another disease I worried about I would have to consider the pros and cons but would probably end up playing the "it won't happen to me" card.

[NobbyNobbs]

Originally Posted by Lothian

It should, but there is a known link between high risk groups and getting the disease.

You brought me up short here. This seems self-evident, redundant, and repititious. Isn't the very definition of a "high risk group" one that is linked to getting the disease?

[Lothian]

Originally Posted by NobbyNobbs

You brought me up short here. This seems self-evident, redundant, and repititious. Isn't the very definition of a "high risk group" one that is linked to getting the disease?

Yes, guilty.

[Careyp74]

ok, with the new numbers the difference is .2806%

Lo, I said a bit off because you had a decimal place wrong

The point is, I can't believe anyone is taking this study as meaningful in any way! The expectation of getting one result when compared to another is highly likely, 98% if I am reading it right?

What if it was a subject closer to many of your hearts?

Suppose I guessed the next card in a stack of 158 decks of cards. I got 51 right. Then I did the same thing, but this time with a Q-Ray bracelet on. Now I guessed 74 right. Anyone want to say that there is any effect at all from the bracelet?

[fls]

Originally Posted by Lothian

It should, but there is a known link between high risk groups and getting the disease. Whether this treatment stops it is not known.

This doesn't make sense to me. Why wouldn't it have been people at high risk of acquiring HIV which acquired HIV in this study?

Quote:

The difference seems very low; 0.024% less chance of getting HIV in the treatment group.

The difference was 0.28%, which is very low. But this is because the underlying rate of acquisition is very low. If you wish to compare the reduction in a way that does not depend upon the rate of acquisition, then you need to use the relative risk reduction, which is 31%.

Quote:

I wonder if it could be down to other factors than the treatment. I appreciate that there are limits to what can be done to ensure the two groups are similar and that with 16,000 starting this trial I can't really expect a bigger one. It is the confidence factor that I don't understand. Can we say as result of this that we are 100% certain that this treatment lowers the risk or a case where we are only 50% certain?

The probability that the vaccine is effective, based on this study, is 97% (if I understand your question correctly).

Linda

[fls]

Originally Posted by Careyp74

I would expect that another trial with 100,000 would show no difference at all between inoculation and placebo.

Why?

Linda

[Careyp74]

linda, your last statement may be backwards, 97% is the confidence that if the norm is 51 out of 8200, you can get 74 out of 8200. Therefore, ineffective. Another trial of 100,000 would bring the numbers closer together, showing how ineffective the inoculation actually is.

[fls]

Originally Posted by Lothian

My choice of percentage was quite deliberate. I have just finished rereading Ben Goldacre’s ‘Bad science’ book. He suggests that comparative percentages can be misleading and it is far better to express them in terms of absolute risk.

Not really. Sometimes absolute risk is useful, sometimes it's relative risk. There are substantial disadvantages to using absolute risk reduction, as it prevents you from being able to use the information on any group except the one represented by the study. In particular, it is very difficult to compare interventions like vaccination or surgery, which are used once, using absolute risk reduction, since the numbers will vary widely depending upon the base rate of your outcome and the length of the follow-up period - two factors which have nothing to do with the effectiveness of the intervention itself. Relative risk reduction does not suffer from those constraints. If you want to compare treatments or compare treatments in different populations, relative risk gives you far more flexibility. On the other hand, it is difficult to put the results into perspective if you use relative risk reduction when your outcome is rare (as in this case). It is best to simply report both.

Quote:

Thanks, I realise that, and I realise that my 50% example was just as unrealistic. I was hoping someone would know how to work out the confidence from the numbers in the article.

Using the study power, p-value, and study type (adequately powered RCT), one can calculate the probability that the study result is a true-positive using this model:

http://www.plosmedicine.org/article/...l.pmed.0020124

Linda