What Comes After Phase III?

If you answered "Phase IV," you're sorta right.

In most cases, the results of a large Phase III trial are submitted to the Food and Drug Administration with all other available information by the sponsor of the drug or device being tested. The FDA considers all of the data and makes a determination regarding approval of the product for marketing.

For a number of reasons, it may be determined that further data are desired. Perhaps the sponsor would like to make a particular advertising claim about the product, but the existing data, while proving the safety and effectiveness of the product to the satisfaction of the FDA, do not fully support the claim. So the sponsor may decide to conduct another clinical trial to specifically demonstrate some feature of the product so that future advertising may include the claim, leading to increased sales. Such additional clinical research is sometimes referred to as Phase IV research.

Similarly, the sponsor may wish to carefully measure certain side effects of the product in wide use. In such a case, a Phase IV trial is conducted following the initial introduction of the product to the market. Also known as "Post-Marketing" studies, Phase IV data are also sometimes used to suggest improvements to be made in a product.

Whatever the motivation, all of the rules for Phase IV clinical trials are the same as for Phase I, II and III research. Participation is voluntary. And the data are collected and analyzed according to predetermined statistical models.

There is a role for Phase IV studies. The defining feature is that they usually occur after a product has entered the market.

-Joe

Related Topics: Sorting Through The Latest Studies, What is a Clinical Trial?

Technorati Tags: clinicaltrials, phase3trial, phase4trials

What's In a Phase?

We often hear of a clinical trial described as being a 'Phase I' (or 'Phase II or III') study. What does this numbering system mean?

First of all, the Phase nomenclature is only used in clinical trials -- research involving human participants designed to test a drug or device that is to be marketed for use in people. And clinical research doesn't usually begin until tests in the laboratory and tests using animals, known as 'pre-clinical' research, have generated promising results.

The Phases are really just steps along the way from early and scarce information to more complete and plentiful information about how a drug or device can be expected to affect patients. In order...

Phase I studies involve few participants and are primarily designed to test the safety of the product. They answer questions such as "Will the product make people sick? If so, how sick?" and "How much of the product can people take before they get sick from it?" Remember, there is already some evidence from pre-clinical studies to suggest that the product will work. The issue for the Phase I study is what doses are relatively safe to use in people.

Phase II studies involve larger numbers of participants. They continue to look at safety -- for effects that didn't show up in the relatively small number of participants in the Phase I trial. But they also are designed to demonstrate how well the drug works at various dosages. Sometimes referred to as 'Efficacy' studies, Phase II clinical trials show how effective the drug is in different doses.

Phase III studies usually include very large numbers of participants. Conditions such as dosages and drug formulation (what form the drug is in, such as a pill or capsule or liquid) are tested in lots of people. This gives a fairly good idea of how well the product will work, what the usual side effects will be (that's what the gazillion things listed on the warning label are), and sometimes longer term observations are made.

Next time: What happens following Phase III...

-Joe

Related Topics: FDA Approves New Angina Drug, FDA Approves Rotavirus Vaccine

Technorati Tags: clinical trials, phases

Results of the Low Dietary Fat WHI Clinical Trial

The news reports last week picked up on the surprising fact (surprising to many of us, anyway) that a low fat diet does not decrease the incidence of invasive breast cancer in post-menopausal women. The prevailing wisdom was, of course, that a low fat diet was good for, well... everything.

But the Women's Health Initiative Randomized Controlled Dietary Modification Trial, published in the Journal of the American Medical Association, measured no statistically significant reduction in invasive breast cancer between nearly 20,000 women who reduced their fat intake and 30,000 women who did not alter their diets. There was a slightly lower incidence, but not enough to be certain that the difference wasn't caused by random chance.

A closer look at the data, however, did provide some evidence for a benefit of a low fat diet. Those women who began the clinical trial with particularly high amounts of fat in their diets demonstrated a wider difference in cancer incidence between the experimental and control groups. This would suggest that dietary fat does play some role, but perhaps only when fat intake is reduced by a relatively large amount.

Does the seemingly "negative" result mean the clinical trial was not helpful? I don't think so. There were many other variables measured in this very important and impressive study. Because of the care with which it was designed and executed, much has been learned that will lead to further research. Equally significant, perhaps, is the spotlight it has focused on women's health.

-Joe

Related Topics: Healthy Eating, Cancer Information

Technorati Tags: lowfatdiet, cancer, women,

Designing the Low-Fat / Breast Cancer Clinical Trial

This clinical trial, known as The Women's Health Initiative Randomized Controlled Dietary Modification Trial, lasted twelve years and included 48,835 participants. Why so many and why so long?

Realize that this study was designed in the early 1990s which means, of course, that the investigators were using what was understood about dietary fat and breast cancer at that time. It was considered such an important question that the investigators were willing to devote more than a decade of their careers and the National Institutes of Health was willing to fund such a colossal project.

All of the women were observed for as long as they were in the study. Some were simply given the standard advice to watch their diet and were given some pamphlets on diet to take home. Others underwent what is known as an "intervention,' which had been proven effective in lowering dietary fat already. In this case, it was a series of intense training in low fat diets and regular meetings in groups to reinforce their low fat eating habits. The group that was only observed is called the "control" group; the one receiving the training and meetings is the "experimental" group.

Statistical calculations were made to determine how many and how long. It was decided that ten years would be long enough to follow these women, who ranged in age from 50 to 79 years. Previous research had suggested that ten years would be long enough for the dietary differences to have an effect. The study lasted twelve years because it took two years to recruit enough participants. The ten-year period, combined with the large number of participants, would also be long enough for some of the women in the control group to develop breast cancer - a morbid concept, but one that is tolerated in studies designed this way. Any decrease in breast cancer in the experimental group would be measurable by comparing the two groups.

Next time: Interpreting the Results

-Joe

Related Topics: The Sonoma Diet: Promoting a Lifestyle, 5 Super Nutrients for Living Longer

Technorati Tags: breast cancer, low fat diet

So Fat In Our Diet Is OK Now?

The news has been full of commentary on a clinical trial just published in the Journal of the American Medical Association (JAMA). It's in the news because the results seemed surprising. Apparently, lowering dietary fat doesn't significantly lower the risk of breast cancer. The study was done on post-menopausal women, a lot of them. Check out the abstract: JAMA. This clinical trial is an excellent example of how medical research is conducted, published and reacted to.

The first thing to notice is that the title does not say anything about the result. "Low-Fat Dietary Pattern and Risk of Invasive Breast Cancer" tells the reader what the study is about, not what the study shows. If this were a newspaper or magazine article, the title might be something like "Lowering Dietary Fat Does Not Reduce the Risk of Breast Cancer." That may be more of a hook, but it's not the way scientific results are published.

Next, take a look at the number of authors - I lost count after 40! Authorship in science is different that in the news media. Everyone who contributes substantially to the research is generally eligible for authorship. Everyone, that is, except for the research participants themselves. In this case, though, there would be an additional 48,835 author...

Next time: how the study was designed.

-Joe

Technorati Tags: lowfatdiet, breastcancer, postmenopause

Informed Consent -- A Process, Not a Piece of Paper

Before someone may be enrolled in a clinical trial, they must give what is known as their informed consent.

That is, they must be fully informed about the research they are considering participating in and they must be given the opportunity to choose freely to participate or not to participate.

It would be great if all clinical trials could be explained to potential subjects in a brief and easy-to-understand way. Actually, they are supposed to be explained as simply, but completely, as possible. But it doesn't always turn out that way.

Science is not simple. It usually takes many words to provide a full and comprehensible explanation to individuals who are not assumed to know the science or the medicine involved. That is why best practices include an oral as well as a written description of the clinical trial.

First, a member of the study team, often a nurse coordinator or a physician, explains the purpose of the research, what will happen to participants and what is known about the benefits and risks involved. This oral explanation could be a one-on-one conversation, a presentation to a group of potential participants, or a video or audio presentation. A key aspect of any oral explanation is that potential participants are given an opportunity to ask questions and have them answered before they make their decisions.

Next, the potential participant is given a written document, referred to as a Consent Form, to read and sign. This Consent Form is often rather long, primarily because it is supposed to contain the information needed to make an informed decision about whether or not to participate. It is signed because it documents the voluntary participation of the research subjects.

No one should agree to be in a clinical trial if they do not feel they know enough about what they are getting into. If you feel you have not received sufficient information to make a decision you are comfortable with and your questions are not answered to your satisfaction, then do not volunteer to participate.

If all goes as it should, the Informed Consent Process -- conversations with the study team and a review of the Consent Form-- should enable you to make a truly informed decision to participate or not participate.

-Joe

Related Links: FDA Approves New Vaccine for Kids' Diarrhea, Health Groups Want Tougher FDA

Technorati Tags: informed consent, consent forms, clinical trials