Clinical Trials

[+ WmClarke]

Do clinical trials always have placebos for some of the participants?

[whipped guy]

Do clinical trials always have placebos for some of the participants?

That is usually the case if the study is to be trusted as being statistically valid. That's were the term placebo effect derives from where an inactive substance seems to "improve" a patients condition. That more or less equalizes things and makes the results of the study more meaningful. In a nutshell it aids in determining the statistical results of the study.

 

Statistics was never my best subject so I defer to others to take it from here!

[+ WmClarke]

That is usually the case. That's were the term placebo effect derives from where an inactive substance seems to "improve" a patients condition. That more or less equalizes things and makes the results if the study more meaningful. It aids in determining the statistical results of the study.

Unless it's a standard lie (and I find it hard to believe that, given all of the other ethical issues the doc has brought up), it will be the real deal with no chance of a placebo. In this case, anyway.

 

Yay, science!

[whipped guy]

PS to the above: Studies are also "double blind" that way neither the participants or the persons administering the clinical trial have any information that may influence the results. As such nobody participating in the testing has a clue who is or is not getting the placebo vs. the actual drug being tested. That is revealed at the conclusion of the study.

 

PS to the PS!!!! So I'm not sure what to believe as I added the PS before reading your posting right above! ?!?!?

[+ quoththeraven]

Do clinical trials always have placebos for some of the participants?

 

If it's to be statistically valid and scientifically rigorous, yes, there will be placebos and the study will be double-blind, as WG discusses above.

 

With some classes of drugs (painkillers, IIRC), placebo effectiveness is so high that it's become difficult for manufacturers to demonstrate effectiveness of new drugs that exceeds that of placebos at a statistically significant level.

[whipped guy]

If it's to be statistically valid and scientifically rigorous, yes, there will be placebos and the study will be double-blind, as WG discusses above.

 

With some classes of drugs (painkillers, IIRC), placebo effectiveness is so high that it's become difficult for manufacturers to demonstrate effectiveness of new drugs that exceeds that of placebos at a statistically significant level.

 

Just to avoid confusion having been on the fringes of the medical profession over the years I had a certain number of patients who partook in various clinal trials. For some reason all seemed to think that they got the "real thing" as opposed to the placebo. I'm not sure how they got this impression, but that always seemed to be the case. Perhaps it was wishful thinking on their part.

 

Plus QTR is right. In fact we all had to take a course in statistics so that when confronted with clinical studies sponsored by drug manufacturers we would (hopefully) be able to determine if the claimed results were statistically significant. It is amazing the tricks that can be used to get something to seem statistically valid. My favorite is when they compare apples to oranges. As such the results seem to be valid, but are in essence worthless.

[+ WmClarke]

PS to the above: Studies are also "double blind" that way neither the participants or the persons administering the clinical trial have any information that may influence the results. As such nobody participating in the testing has a clue who is or is not getting the placebo vs. the actual drug being tested. That is revealed at the conclusion of the study.

 

PS to the PS!!!! So I'm not sure what to believe as I added the PS before reading your posting right above! ?!?!?

I know!

 

I'm going to go with "the doc doesn't lie" since he was upfront about so many things--so it wil not be a placebo. Can't really worry about it. You get a chance; you take it.

[+ Rickee]

The Randomized Control Trial is essentially the standard for medical research (and one of the defining aspects of the RCT is the control, or "placebo"). With that said, some medical practitioners question the ethics of withholding potentially life-saving protocols if they appeared to exhibit significant benefits in the earlier stages of testing (i.e., before getting to the clinical trail stage).

 

I would directly question the attending physician as to how/why this clinical trial is apparently not following the typical RCT path. There may be a very valid (and hopeful) answer!

[+ WmClarke]

If it's to be statistically valid and scientifically rigorous, yes, there will be placebos and the study will be double-blind, as WG discusses above.

That's what I thought I remembered from stats courses in grad school.

[+ WmClarke]

The Randomized Control Trial is essentially the standard for medical research (and one of the defining aspects of the RCT is the control, or "placebo"). With that said, some medical practitioners question the ethics of withholding potentially life-saving protocols if they appeared to exhibit significant benefits in the earlier stages of testing (i.e., before getting to the clinical trail stage).

 

I would directly question the attending physician as to how/why this clinical trial is apparently not following the typical RCT path. There may be a very valid (and hopeful) answer!

So many questions.......

[whipped guy]

I know!

 

I'm going to go with "the doc doesn't lie" since he was upfront about so many things--so it wil not be a placebo. Can't really worry about it. You get a chance; you take it.

Exactly!!!!! You got the chance! Take it! Run with it! Go for the max!!!

[gallahadesquire]

It sometimes depends on the drug and trial. Sometimes there will be an "active control", meaning it has similar effects to the trial drug, but without the therapeutic effects. Sometimes the study has to be open, and (for instance, in chemotherapy) the study drug is included / not included in the mix. To blind it to the practitioner, the side effects should be similar.

 

Sigh. I haven't read medical literature in five years, but it seems all the "statistical tests" (chi-square, t-test, Bonferroni correction for multiple comparisons, etc.) have gone the way of the odds calculation. This is especially true of meta analyses, which are increasingly necessary due to the small number of test subjects in any given group.

 

What is an odds ratio?

An odds ratio (OR) is a measure of association between an exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure. Odds ratios are most commonly used in case-control studies, however they can also be used in cross-sectional and cohort study designs as well (with some modifications and/or assumptions).

 

Odds ratios and logistic regression

When a logistic regression is calculated, the regression coefficient (b1) is the estimated increase in the log odds of the outcome per unit increase in the value of the exposure. In other words, the exponential function of the regression coefficient (eb1) is the odds ratio associated with a one-unit increase in the exposure.

 

Go to:

When is it used?

Odds ratios are used to compare the relative odds of the occurrence of the outcome of interest (e.g. disease or disorder), given exposure to the variable of interest (e.g. health characteristic, aspect of medical history). The odds ratio can also be used to determine whether a particular exposure is a risk factor for a particular outcome, and to compare the magnitude of various risk factors for that outcome.

 

• OR=1 Exposure does not affect odds of outcome
  
• OR>1 Exposure associated with higher odds of outcome
  
• OR<1 Exposure associated with lower odds of outcome
  

Go to:

What about confidence intervals?

The 95% confidence interval (CI) is used to estimate the precision of the OR. A large CI indicates a low level of precision of the OR, whereas a small CI indicates a higher precision of the OR. It is important to note however, that unlike the p value, the 95% CI does not report a measure’s statistical significance. In practice, the 95% CI is often used as a proxy for the presence of statistical significance if it does not overlap the null value (e.g. OR=1). Nevertheless, it would be inappropriate to interpret an OR with 95% CI that spans the null value as indicating evidence for lack of association between the exposure and outcome.

[+ quoththeraven]

The Randomized Control Trial is essentially the standard for medical research (and one of the defining aspects of the RCT is the control, or "placebo"). With that said, some medical practitioners question the ethics of withholding potentially life-saving protocols if they appeared to exhibit significant benefits in the earlier stages of testing (i.e., before getting to the clinical trail stage).

 

Clinical trials are cut short if the results are overwhelmingly positive because it is considered unethical to withhold demonstrably effective treatment that is superior to existing treatment, or if no treatment exists. But I would argue that even if no treatment exists, it is also unethical to skip clinical trials, and that any move to make a promising treatment for a condition without any available in advance of a clinical trial must be accompanied by rigorous disclosure, including of any financial stake the physician has.

 

That's assuming that making an experimental drug available at that stage is even legal. My concern is that since it won't be covered by insurance, the manufacturer will overcharge for it (i.e., prey on the desire for an effective treatment) and only the rich and well-connected will benefit.

[whipped guy]

It sometimes depends on the drug and trial. Sometimes there will be an "active control", meaning it has similar effects to the trial drug, but without the therapeutic effects. Sometimes the study has to be open, and (for instance, in chemotherapy) the study drug is included / not included in the mix. To blind it to the practitioner, the side effects should be similar.

 

Sigh. I haven't read medical literature in five years, but it seems all the "statistical tests" (chi-square, t-test, Bonferroni correction for multiple comparisons, etc.) have gone the way of the odds calculation. This is especially true of meta analyses, which are increasingly necessary due to the small number of test subjects in any given group.

 

What is an odds ratio?

An odds ratio (OR) is a measure of association between an exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure. Odds ratios are most commonly used in case-control studies, however they can also be used in cross-sectional and cohort study designs as well (with some modifications and/or assumptions).

 

Odds ratios and logistic regression

When a logistic regression is calculated, the regression coefficient (b1) is the estimated increase in the log odds of the outcome per unit increase in the value of the exposure. In other words, the exponential function of the regression coefficient (eb1) is the odds ratio associated with a one-unit increase in the exposure.

 

Go to:

When is it used?

Odds ratios are used to compare the relative odds of the occurrence of the outcome of interest (e.g. disease or disorder), given exposure to the variable of interest (e.g. health characteristic, aspect of medical history). The odds ratio can also be used to determine whether a particular exposure is a risk factor for a particular outcome, and to compare the magnitude of various risk factors for that outcome.

 

• OR=1 Exposure does not affect odds of outcome
  
• OR>1 Exposure associated with higher odds of outcome
  
• OR<1 Exposure associated with lower odds of outcome
  

Go to:

What about confidence intervals?

The 95% confidence interval (CI) is used to estimate the precision of the OR. A large CI indicates a low level of precision of the OR, whereas a small CI indicates a higher precision of the OR. It is important to note however, that unlike the p value, the 95% CI does not report a measure’s statistical significance. In practice, the 95% CI is often used as a proxy for the presence of statistical significance if it does not overlap the null value (e.g. OR=1). Nevertheless, it would be inappropriate to interpret an OR with 95% CI that spans the null value as indicating evidence for lack of association between the exposure and outcome.

Now I know why statistics was not my favorite subject. I recall getting this same headache forty some odd years ago when we took classes with medical students! . It was worse than pulling teeth from my perspective!!!!!

[+ purplekow]

Clinical trials do not always use placebos. If there is a standard treatment which is well established, that may serve as the baseline and the new regimen may be tested against that. So rather than getting an inert drug, one either gets the standard treatment or, the standard treatment and/or the test drug.

[+ quoththeraven]

Clinical trials do not always use placebos. If there is a standard treatment which is well established, that may serve as the baseline and the new regimen may be tested against that. So rather than getting an inert drug, one either gets the standard treatment or, the standard treatment and/or the test drug.

 

Wouldn't the study still need to be double blind?

[+ purplekow]

Wouldn't the study still need to be double blind?

Yes trials are usually double blind with a code so that results can be interpreted as the information comes in. Those calculations are not done by the people who are actually distributing the medication or performing the treatment. I have done a variety of clinical trials and i have never been informed which leg my patient is being randomized to join. I am told this patient gets a certain sample number without foreknowledge of what is in that sample.

[+ WmClarke]

So I did get an answer for this particular case. The doctor said that there was no chance of a placebo for two reasons.

 

First, this is not a trial for a drug to treat a specific disease. Since it is for any type of cancer (including leukemia) this design of this study does not use control groups.

 

Second (and I think this is a biggie), in the US it is illegal to withhold a drug treatment for a cancer patient. So even stage 1 clinical trials do not use placebos if it is a trial for a cancer treatment.

 

So that's what the doctor told us.

[+ quoththeraven]

So I did get an answer for this particular case. The doctor said that there was no chance of a placebo for two reasons.

 

First, this is not a trial for a drug to treat a specific disease. Since it is for any type of cancer (including leukemia) this design of this study does not use control groups.

 

Second (and I think this is a biggie), in the US it is illegal to withhold a drug treatment for a cancer patient. So even stage 1 clinical trials do not use placebos if it is a trial for a cancer treatment.

 

So that's what the doctor told us.

 

So when there is a treatment, clinical trials test whether they're better than existing treatments. I should have realized that.

 

I knew a cancer patient eho was in a clinical trial, but he was dropped early on for not meeting clinical criteria. (I think his white cell count was too high.)

 

Thanks for letting us know.

[+ bigjoey]

So I did get an answer for this particular case. The doctor said that there was no chance of a placebo for two reasons.

 

First, this is not a trial for a drug to treat a specific disease. Since it is for any type of cancer (including leukemia) this design of this study does not use control groups.

 

Second (and I think this is a biggie), in the US it is illegal to withhold a drug treatment for a cancer patient. So even stage 1 clinical trials do not use placebos if it is a trial for a cancer treatment.

 

So that's what the doctor told us.

 

My mother had non-Hodgkins lymphoma and was in the first group of patients in a trial study for Rituxan at MD Anderson under Dr Michael Keating. As I recall, there were about 25 or so patients in the trial group. I do not remember a control group. I do not remember the exact time line now but if I recall correctly, the clinical trial showed such amazing results that the clinical trial was cut short and Rituxan put into general use and shortly became the main drug to fight that lymphoma. At least, that is my memory. My mother's doctor up here in Kansas City felt it was a "miracle" drug and it gave my mother an added ten years to her original prognosis time line.

 

[As an aside, the care at MD Anderson was beyond wonderful. My sister and I still send them donations each year as a "thank you" for the excellent care they gave our mother. Even the food was first rate which is unusual for a hospital. I can not say enough nice things about the staff at that hospital.]

[gallahadesquire]

Clinical trials do not always use placebos. If there is a standard treatment which is well established, that may serve as the baseline and the new regimen may be tested against that. So rather than getting an inert drug, one either gets the standard treatment or, the standard treatment and/or the test drug.

In this case, the placebo is "standard care" and the test protocol is "standard card plus [xx]

[MrMattBig]

A placebo tends to be used to test if the results are, or can be, brought on by a psychological means versus pharmacological. At any rate, in an experiment or clinical trial, there is always a control variable to compare the results of the treatment to and illustrate it's effectiveness.