Glenn Ellis

*Clinical trials are a vital and necessary part of America’s medical research system. They have proven to be the best mechanism for testing potential drugs and separating the ones that work from the ones that are ineffective or potentially harmful.

It usually takes 12–15 years for a new compound to be approved as a medicine in the United States. On average, it costs $800 million for a pharmaceutical company to develop a new medicine. Typically, a pharmaceutical company recoups its development costs for only three of ten medicines.

Before 1938, manufacturers could market a drug without submitting any information to the FDA or any other agency; the Federal Food, Drug and Cosmetic Act (FD&C Act) of 1938 was passed when over 100 children died from taking a sulfa drug that had not been tested in people.

One of the major events that brought the issue of clinical trials to the public was the revelation of the Tuskegee Syphilis Study. The study was conducted by the United States Public Health Service. The Tuskegee study began in 1932 and continued till 1972, when it was revealed to the public. The purpose of the study was to examine the long term affects of syphilis. The subjects of the study were 400 African American males, who were primarily poor sharecroppers. These men all had syphilis, but were unaware of it. They were also unaware of the true nature of the experiment. The most horrifying aspect of the experiment was in the 1950’s penicillin was proved to be effective at curing syphilis. The researchers did not treat the syphilis and even prevented other doctors who saw the participants from treating the syphilis. As many as one hundred men may have died from complications from their untreated syphilis. The study was revealed in 1972 by a newspaper article shocked the country and caused the project to be shut down. It wasn’t until 1997 that President Clinton formally apologized for the study.

Many of the early advances in medicine were made at the expense of many marginal groups such as asylum inmates and prisoners. These test subjects were involved in these clinical trials without being informed, or even asked.

Informed consent is one of the most important “safety nets” in clinical trials. Doctors are obligated to make sure that a patient understands the risks and benefits of any medical procedure. Requiring informed consent protects many marginal groups from being forced to participate in medical studies without understanding the risks involved. Medical advances should not require some people to sacrifice their health and rights for the good of all. Informed consent is a key instrument in protecting these rights.

At the start of the four “Phase” clinical drug trial, developers concentrate on the tolerability of a new drug. These Phase I studies are usually carried out on a small number (20–100) of healthy volunteers. The aim of Phase II studies, which include 100 to 500 patients, is to determine whether the new drug is effective in the disease for which it is intended and what its potential side effects are. Phase II studies also serve to determine the dosage range, i.e. the highest tolerable and lowest effective doses, for the subsequent large-scale Phase III studies.

To this end, the patients are divided into two study groups. One patient group (the drug group) receives the drug being tested, while the other (the control group) receives a standard medication or placebo (placebo group). A placebo is a dummy pill, tablet, capsule, or solution that is identical in color and taste to the drug but contains no active ingredient.

For ethical reasons, in the case of severe and life-threatening diseases such as cancer and Aids, both groups continue to take their standard medications as well as the new drug or placebo.

Most clinical drug trials are based on a “blind” design, i.e. the patients are unaware which group they have been assigned to. In many cases, moreover, neither the patients nor the developers know who is receiving the test drug. Such trials are referred to as double-blind studies.

Phase III studies are carried out on large groups of patients (1,000 to 5,000) for whom the new drug is ultimately intended. The inclusion criteria that determine which patients can be enrolled in the study are often less stringent than in Phase II. Patients who differ in terms of gender, age, ethnic origin, lifestyle, diet, and state of health are randomly selected.

In order to recruit the large number of voluntary patients required, the studies are usually organized on at a number of hospitals and medical practices.

Once approval has been granted by the regulatory authorities, the pharmaceutical company is allowed to market the drug. Even then, however, the manufacturer has to submit to the regulatory authorities a precisely scheduled series of reports (phase IV) to document very rare side effects of the drug which occur in, say, only out one of 20,000 cases and which can therefore escape notice even in the Phase III trials.

As beneficial as clinical trials are, there are concerns. In all things you must “follow the money”.

Costing upwards of a half billion dollars, and taking up to ten years before any return on investment, the stakes are indeed high.  Private corporations, not the government, have been the largest sponsors of pharmaceutical research in both the United States in the last twenty years.

While doctors have a right to be reasonably remunerated for the work they perform, inappropriate remuneration raises the possibilities of:

• Erosion of the patient’s informed consent;

• Enrolment of ineligible subjects or subjects on the margins of eligibility;

• A coercive enrollment environment, e.g., patients agreeing to be subjects simply because they fear losing the caregiver if they say ‘no’; and

• Doctors, under pressure to increase their income, being inclined to perform research that they are not qualified to do.

Never feel pressured into joining a clinical trial. If your questions are not fully answered by the research nurse or doctor at the outset, discuss the benefits and risks of participating with your family doctor before signing a consent form.

If you have any concerns during the trial, contact the clinician in charge or the head of the institution’s ethics committee that approved the trial. (You should have been given the committee’s telephone number). If the ethical approval was by a for-profit company, seek advice from your family physician as to whether it’s advisable to continue in the trial.

You can withdraw from the study at any time for whatever reason. If you plan to stop participating, you might let the research team know why you are leaving the study, although you are not required to explain your decision for withdrawing to anyone.

 

Here are some other questions to keep in mind about clinical trials: Do they offer false hope? Do enough people take part? Is it better or worse if a study is funded by a large pharmaceutical company?

I don’t think much has been written about this topic, but it’s time we started talking… and thinking.

Remember, I’m not a doctor. I just sound like one.

Take good care of yourself and live the best life possible!

Glenn Ellis lectures and is an active media contributor nationally and internationally on health related topics, including health education and health promotion.

For more good health information, visit: www.glennellis.com