Understanding Clinical Trials


The more research studies that I read the more confused the issues become. Take my post from last week as an example: Asparagus & Cancer Cell Growth Even with my explanations some of you came away confused. I understand that. Because of that post, this week I am going to talk about how research, in particular clinical trials, are done.

The headlines in the news tend to be sensational & scare the **** out of us. I don’t think that the researchers are trying to upset us or confuse us. They are just reporting on their findings. We want to know that studies on mice show that some nutrients, given in larger amounts, will cause cancer or that some, given in smaller than normal amounts, may block the cancer cells ability to metastasize. But…before we go crazy trying to decide what this means to our diet, we need to take a breath & step away. We need to wait for several, not just one, clinical trials on humans to then make adjustments to our lifestyles. Even then we need to talk this over with our health care team to determine if the benefits outweigh the risks for us as an individual.

What is the difference between basic research studies & clinical trials? Research studies are experiments that have been conducted in a laboratory setting usually using non-human subjects. These experiments can be at a cellular level in a petri dish or done on mice/rats etc. 

Clinical trials are done with human volunteers in order to prove a theory that was developed in the laboratory about treatments for diseases. Your healthcare team may be aware of a Clinical trial being conducted that you could benefit from. Talk to them first. 

There are several governmental agencies which oversee clinical trials. They are in place for the protection of those volunteer subjects & also to list the clinical trials that have been done, are currently going on & those which need volunteers.

The U.S. Department of Health & Human Services has a watch-group called the Office for Human Research ProtectionsThe Office for Human Research Protections (OHRP) provides leadership in the protection of the rights, welfare, and wellbeing of human subjects involved in research conducted or supported by the U.S. Department of Health and Human Services (HHS). OHRP is part of the Office of the Assistant Secretary for Health in the Office of the Secretary of HHS.

OHRP provides clarification and guidance, develops educational programs and materials, maintains regulatory oversight, and provides advice on ethical and regulatory issues in biomedical and behavioral research. OHRP also supports the Secretary’s Advisory Committee on Human Research Protections (SACHRP), which advises the HHS Secretary on issues related to protecting human subjects in research.

On this page, About Research Participation, OHRP has the following information. If you have an interest in being part of a clinical trial this is a good place to start to understand the protections that are in place.

  • Informational videos about research participation. 
  • A list of questions to ask the researchers of the study you are interested in.
  • Information about the regulations protecting you as a subject in a clinical trial.
  • Resources outside of OHRP to help you in understanding research involving human subjects.

There is another safeguard that has been set up. It is called the IRB, Institutional Review Board. The FDA has a site that answers questions about the IRB if you are interested: Institutional Review Boards Frequently Asked Questions -Information Sheet. The first question is probably all you need to know 🙂

1. What is an Institutional Review Board (IRB)?

Under FDA regulations, an IRB is an appropriately constituted group that has been formally designated to review and monitor biomedical research involving human subjects. In accordance with FDA regulations, an IRB has the authority to approve, require modifications in (to secure approval), or disapprove research. This group review serves an important role in the protection of the rights and welfare of human research subjects.

The purpose of IRB review is to assure, both in advance and by periodic review, that appropriate steps are taken to protect the rights and welfare of humans participating as subjects in the research. To accomplish this purpose, IRBs use a group process to review research protocols and related materials (e.g., informed consent documents and investigator brochures) to ensure protection of the rights and welfare of human subjects of research.

Clinical trials are usually done in phases. I will use the word “drug”, but this applies to drugs, devices, procedures, nutrients, diets…you get the idea 🙂

  • Phase 0: This phase is more of an “exploratory phase”. Say a drug company wants to speed up the clinical trial process to get their drug approved. They would use this phase to try micro-doses on a few human subjects to determine if they should continue with a full clinical trial.
  • Phase 1: This phase is done on a group of healthy human subjects to determine if a drug is safe. It is also used to decide on the highest dose that causes the least side effects. This may take months.
  • Phase 2: They then move on to this phase to determine if the drug actually works on the targeted disease & its safety at this dose. It is given to human subjects with that particular disease. This phase can also have two groups. One that takes the drug & one that is given a placebo. This phase can last for a year or more.
  • Phase 3: When & if a drug gets to this phase, several hundred or even thousands of human subjects will be used. It is to obtain a more accurate picture of the drugs effectiveness & adverse affects on a broader range of people. 
  • At this point the company can apply to the FDA for approval of the drug.
  • Phase 4: The drug has now been approved for use in the U.S. This phase is used if the company wants to compare its new drug to other drugs that are on the market, look at the long term affect on a persons quality of life or look at the cost effectiveness. Thousands of people take part for many years. At this point the drug still may be taken off the market by the FDA after evaluating the above information.

***My resources for the above list:

  1. American Cancer Society: What Are the Phases of Clinical Trials
  2. Center Watch: Overview of Clinical Trials

If you are interested in participating in a clinical trial there are a lot of questions to ask. For example who is responsible for the cost of the trial & do you as a participant bear any responsibility. I found this next site from the NIH: National Cancer Institute, to be the best one to answer those questions. It also has a page to help you find clinical trials for cancer patients.

Clinical Trials Information for Patients and Caregivers  “Clinical trials are research studies that involve people. Understanding what they are can help you decide if a clinical trial might be an option for you. Or maybe you have a friend or family member with cancer and are wondering if a clinical trial is right for them.

We’ve provided basic information about clinical trials to help you understand what’s involved in taking part. This includes information about the benefits and risks, who is responsible for which research costs, and how your safety is protected. Learning all you can about clinical trials can help you talk with your doctor and make a decision that is right for you.

Find NCI-Supported Clinical Trials: You begin by entering your type of cancer, age & zip code to locate clinical trials in your area.  NCI-supported clinical trials are those sponsored or otherwise financially supported by NCI.

See our guide, Steps to Find a Clinical Trial, to learn about options for finding trials not included in NCI’s collection.” This page is very important if you want to find a clinical trial specifically for your type & stage of cancer. It shows you how to gather the information needed & how to find a trial.

On this next website you will be able to access clinical studies from the U.S. & other countries. You will choose all studies or current studies underway or those recruiting for a study. You will enter your type of cancer or any disease; any other term you want to search under, for example a particular medication; & then you choose a country. If you want to narrow it down more, then choose Advanced Search.

NIH: National Library of Medicine, ClinicalTrials.gov is a database of privately & publicaly funded clinical studies conducted around the world.” Not all of the studies on this site have been evaluated by the U.S. Government. 

As you can see, it sometimes takes years to get from the initial Phase 0 trial to the approval by the FDA. I also read that the time between the end of the Clinical Trial & the publication in a peer review, a conservative estimate, can be 2 years or more. I couldn’t find any time estimate from the initial idea & research on non-human subjects to the publication after clinical trials. It must be more than 5 years I would think.

I asked Google how much it would cost to get a drug approved from the laboratory to clinical trials to approval. The results referred me to an article in the Washington Post about a study asking that same question done by Tufts Center for the Study of Drug Development, a research group partially funded by drug makers. Does it really cost $2.6 billion to develop a new drug?  November 18, 2014  

The debate over the actual cost is in the article. Some people claim that this study was done to justify the high prices of drugs. Others say that the Federal Government has grants for studies that are paid for out of our taxes, and this money was not included. Regardless of who is right, it costs close to a billion dollars for drug companies to do these studies. They have a lot invested in the outcome. Hence the oversight committees that are put in place. 

When I look at a study that has made the news, I try to find the original paper. These are the points that I then look at…

  • Who conducted & authored the study. 
  • Where was the study conducted. University? Drug Company laboratory?
  • What country was the study done in.
  • If it was a clinical trial I check to see who the participants were, how many were in the trial & how long it lasted. I check for the gender & age group. I also check to see how it was done; self reporting is less accurate than monitored.
  • Who paid for the study. This is very important to find out. If it is a study on sugar & the sugar industry paid for the study, we need to know that.
  • I look at the purpose of the review. Sometimes the news media misinterprets this.
  • I check the Introduction to see what they have to say about this research.
  • I read the conclusions. Usually they say either there needs to be more studies done or that they are now going to clinical trials. 
  • At the bottom of an abstract paper is a section that shows “conflict of interest”. Here is an example from a meta analysis that the NIH & NCBI published in 2016 called: Relationship between Added Sugars Consumption and Chronic Disease Risk Factors: Current Understanding  Conflicts of Interest: J.M. Rippe’s research laboratory has received unrestricted grants and J.M. Rippe has received consulting fees from ConAgra Foods, Kraft Foods, the Florida Department of Citrus, PepsiCo International, The Coca Cola Company, the Corn Refiners Association, Weight Watchers International and various publishers.” Now you see why this is important to know.

I am also very selective about which news group I will read after seeing a headline. I am not going to even look at the National Inquirer for example, but I will read what BBC, CNN, a university or cancer center publication, or a trustworthy site that I like, has to say. Then I “fact check” by reading the original study. It is a lot of work, but it weeds out the **** from the the wonderful studies being done on cancer.

I hope that from this post you can see why, although interesting, results of research on mice should not determine how you eat or how you change your lifestyle. Especially if it means going on some fad restrictive diet or crazy exercise program. We need to wait for the clinical trials. Then, & only then do we check to see if these results apply to us. I am not going to get too excited about changing my diet if the clinical trial was done on men in their 30’s 🙂

Until next week…Mary:)