Clinical Trials - Should We Participate?

Some patients join clinical trials out of desperation, others to advance medicine, others are seeking therapeutic value...Only 5% of clinical trial patients will benefit therefrom; but 85% state their reason for entering the trial was expectation of therapeutic value. Who is to blame if they get sick--or even die? (6)

Forward

As Norman Schwarzkopf recently said in an interview, all of us agree that a ‘cure’ for cancer depends on medical innovation and research. Moreover, it is incontrovertible that successful development of drugs must involve their use on cohorts of living patients afflicted with the disease to which the drug is directed; and such ‘proof’ of the efficacy of a drug depends on our participation as experimental subjects. We can volunteer for any/all trials with the thought that we have a terminal disease and perhaps our unselfish participation will somehow benefit mankind. Or, we can become educated about the process of clinical trials, assure that the one we choose is congruous with our particular needs, and assure that we enter the trial with ‘eyes wide open’ as to what we can expect from our participation.

Your life and health depend on the content and conduct of a trial and your response (or lack thereof) to the trial agent(s)---in my opinion, a patient’s maximum due diligence is required before entering a trial because you are your only advocate in this setting. Below I propose a summary check list of those questions we should ask ourselves before signing a consent form to participate in a clinical trial:

1. What is the purpose of the trial-- to treat the disease, or is it a medical experiment?

2. What phase is the trial?--the earlier the phase, the more experimental.

3. What are the risks?--What are the rewards?--List all potential side-effects.

4. Are other doctors/institutions participating in the trial protocol?--Demand a synopsis of the results to-date in any other arms of the trial.

5. What happens if there are problems or ill effects?---Who is responsible and who pays?

6. What are the qualifications of the principle investigator?---Is he/she trained in the scientific method of conducting experiments?

7. Demand a complete written financial disclosure of all investigators/institutions.

8. Insist that a third party who is familiar with drugs, scientific methods of experiments, and medical protocols review the consent form with you.

...Clinical trials defined (6, 9):

What is a clinical trial? ----research studies to answer scientific questions re prevent, diagnose, or treat cancer; the trials can be for new agents addressing specific cancers, or combinations of new agents + conventional agents, or new combinations/dosing/scheduling of conventional agents.

Types of clinical trials--a) new treatment approaches, b) prevention trials; for agents/supplements applicable to people who have never had cancer, or to prevent recurrence, c) screening trials to discover cancer in its early stages, d) supportive care trials.

How clinical trials are supposed to work: 1) basic research = a hypothesis re why a new agent/procedure might be effective, 2) animal studies, 3) proposal to a review board for approval, 4) recruit patients, 5) inform patients by detailing all potential risks/benefits = signing a consent form, which is a complicated legal document that can be 30 pages, 6) PH I = safety study, dosing and scheduling; a few patients; about 70% of such studies make it to the next phase, 7) PH II studies; usually a few hundred patients; a control group is added to see if the experiment is having effect, 8) PH III; usually involves thousands of patients; usually compares the experiment to existing/conventional treatments and a placebo, 9) FDA approval, 10) PH IV; if the drug/protocol is approved, the applicant must report up to 10 years any unexpected reactions.

Summary

Medical research has expanded significantly in recent years and large clinical drug trials with human subjects are necessary to accelerate the process of getting the drugs to market and into clinical practice. But in the rush to attain large cohorts of patients enrolled for an expanding number of experimental drugs, many of the duties of research scientists have been transferred to clinical practitioners. The roles of research scientists and clinical practitioners differ significantly but are often blurred when considered from the viewpoint of the patients. This blur becomes more opaque as the academic/science research is increasingly influenced by commerce/finances. The burden of assuring high ethical standards and societal trust in these experiments is falling more on the patient to be vigilant in assuring that we are not just a sacrificed means to a financial end.

When recruited for a trial, we must become intimately familiar with the goals of the experiment and realize that they inevitably differ considerably from clinical care for our disease. We must assure that we understand the Consent Form and receive full disclosure of the financial aspects of our participation in the experiment. We must demand that the experiment investigators reveal their remuneration for having recruited us, as well as the details of their relationship with the drug companies and institutions sponsoring the experiment. Moreover it is incumbent on us, as participants in the experiment, to assure that the doctor/investigator is qualified in both the medical practice of the protocol, as well as being qualified as a research scientist; and that the program follows all aspects of research ethics and scientific methods.

Rest assured that you have the responsibility to fully understand the nature of the experiment and whether it might be beneficial for you; and also that the doctor who recruited you for the experiment is fully qualified as a research scientist in addition to being a clinical practitioner.

DISCUSSION

Two decades ago all clinical trials were performed in academic centers and fourteen years was required on average for a new cancer drug to develop from pre-clinical to Phase III human trials.

Much of the tectonic shift in clinical trials of the past few years is driven by the relationship between medical scientific research by drug companies and institutions and their need to accelerate drug development by recruiting large cohorts of patients for experiments. The natural needed expansion of efforts is to recruit our doctors to recruit us as experimental models and today 65-70% of clinical trial accruals originate from community hospitals. To provide this service to cancer science, our doctors receive considerable financial remuneration from drug companies and government agencies, both as a per-head recruitment fee (up to $6,000 per patient recruited), as well as bonuses and administrative costs.

Obviously this creates a conflict between clinical care and compensated research by a practicing doctor who is seldom trained in even the basics of proper scientific research methods; and community oncologists have no guidelines which serve in the approach to patients for participation in a scientific experiment. However, it is recognized that our community doctors have immediate access to the large cohorts of patients needed for the experiments. Notwithstanding the contracted time frame to rush drugs to human trials/market by utilizing community patient pools/doctors, only 3% of cancer patients participate in clinical trials.

Why are patients reluctant to enter trials? Some patients fear that the trials are to satisfy the need to publish, or financially reward the doctor/institution vs. trying to advance the medical science of cancer treatment. Some patients fear the placebo of randomized trials or a perception that they had rather seek standard treatments rather than experiments. Many patients are reluctant because their insurance refuses coverage for the experiment, or any adverse ramifications thereof. Other patients are reluctant to do the required ‘cleansing’ required for trial entry. (4) Also, many reports reflect that the patients who do enter trials are unclear about the objectives of the trial. Less than 5% of the patients in a PH I trial will receive any benefit; yet 85% of those patients stated their reason for entering the trial as expecting therapeutic benefit. (6) Do you agree that before entering a trial and signing the consent form, the burden is ours to perform the maximum due diligence in order to know every aspect of a trial and our exact expectations therefrom?

The professional and legal fiduciary duties of research scientists and medical practitioners are significantly different, as well as their formal academic training: research scientists generate knowledge that might result in drugs/agents that provide clinical therapeutic benefit; our practicing doctors are morally and legally required to focus on our health and welfare. To have our doctors fulfilling both duties simultaneously can certainly present a conflict of interests and can result in divergent objectives that are to our detriment.

Recent dynamic trend changes affecting clinical trials: ..R&D investment by the top 20 drug companies has doubled in the past 7 years...revenues are forecast to grow only 7%/year in the coming years...they must generate $25 billion additional annual sales to maintain current levels of profitability...this requires launching 24 to 34 new drugs per year that cost less to develop or sell at higher prices to maintain profitability... (1)

Academic/institutional centers are slowed by lengthy review processes and large overhead expenses...thus, the requirement for less costly and time-consuming venues...contracting to community-based practicing doctors for patient recruitment and experiments is faster, economic, and provides broad recruitment possibilities...the number of practicing doctors likewise conducting clinical research has increased 600% in 10 years...research in academic/institutional centers has decreased 80% in the past 10 years and shifted to medical practitioners...funding to community-based trials has increased 3-fold in the same time frame. (1) More than 80,000 clinical trials were conducted in the U.S. on 2001. (6)

This transfer of research efforts is accomplished by private organizations who advertise and recruit community hospitals and doctors for their access to the community’s patients. These private organizations are paid by the drug companies; their continued existence is dependent on positive trial results; and the financial viability of the entire chain of funding for the experiment could possibly be compromised by this conflict of financing/profit vs. research integrity and safety of patients participating in the experiment.

While most of the private organizations that recruit and conduct research in a community-based setting are subject to FDA regulation, they often contract to local private review boards for oversight of the projects and these second-tier organizations are not subject to FDA oversight. These secondary organizations are for-profit and their very existence depends on continuous flows of projects to review and thus, another conflict is created as they have the opportunity to use much less stringent review standards.

In 1999 two news articles (10, 11) revealed the result of some of these conflicts and patients were described as "...commodities, bought, sold, and traded by testing companies and doctors." They further revealed that recruiting doctors not even involved in the trial were paid to simply refer patients to the investigator. In some trials, finder’s fees and bonuses for reaching quotas amounted to several thousand dollars/patient. (1) This cascade of recruitment and financing removes the activity from governmental oversight and certainly can result in conflicts of interest that are not in our favor; in fact, it can make us irrelevant in the process, except as a commodity. Several recent clinical trials were suspended (some at prestigious institutions) for breaches of ethical standards, some of which resulted in patients’ deaths.

But, any oversight of the entirety of clinical trials is lost in the myriad of rules, regulations, and non-related government entities. The many government agencies that sponsor research rely on trust that the system will be followed and do not routinely audit programs. Each agency has its own rules and regulations: the NHI; the Office of Management Assessment which must refer violations to the Office of the Inspector General (OIG), which refers them to the Justice Department, who rely on the federal False Claims Act (FCA) for compliance guidelines. For Federally funded research, recipients thereof must agree to disclose ‘significant’ financial interests, establish review procedures for conflict of interests, create proper informed consent forms, and annual certification that the rules and regulations are being followed. But, there is nobody to review or assure compliance with these rules/regulations.

Moreover, once the projects are delegated to private organizations for funding and recruitment of investigators and patients, the research is subject to a completely different set of rules and oversight/review enters a new maze of different regulatory agencies and regulations, but all of these are considered to be in the sphere of the maze of the first agencies/regulations. All of these oversight/review agencies now say that given the increased commercialization of research and the vastly increased number of multicenter trials, an inordinate increase in workload has resulted and therefore, only minimal, sporadic review is possible.

Specifically, the job of the Office for Human Research Protection (OHRP)* is to oversee and monitor clinical trials. In 2001, OHRP had only two full-time investigators to monitor more than 4,000 federally funded research institutions; and each institution has numerous clinical trials in progress. Since 1980 the agency has audited, on average, just four sites per year. During the same time frame, the FDA made 200 site visits to the approximately 1,900 sites that oversee research on FDA-regulated products. (6)

If by chance a possible financial violation is discovered, then the Federal Anti-Kickback statute is relied upon. This generic arcane statute makes it a felony to accept financial incentives from commercial entities (drug companies), or paying trial participants, or paying for the referral of patients covered by Medicare/Medicaid.

Of the 80,000 clinical trials conducted in 2001, a quarter of them received no federal oversight whatsoever; and where oversight is mandatory it is applied loosely (if at all) due to the vast numbers of trials and multicenter locations. (6) I suggest that in no way are we protected by any of the myriad conflicting rules and regulations governing clinical trials and the system is free to conduct the trials in any manner they so desire. As we are recruited for trials, we will be very fortunate if we select and are accepted in one that is being conducted in our best interest.

To repeat, I suggest that it is incumbent on the cancer patient to use the utmost due diligence in researching a trial before we sign a consent form therefor:

1) Study the vast array of agents in trials and understand the generic classification thereof. Is it a vaccine?---Biological Response Modifier?---Signal Transduction Inhibitor (there are 300+ in development)?---Monoclonal Antibody (what is its purpose?; is it labeled with a treatment agent)?---Is the trial agent in conjunction with a treatment agent (chemo/RT)?---etc.

2) What is the cleansing requirement?---most trials require us to be ‘clean’ of treatments at least 30 days before trial initiation and during the trial---can you afford to be ‘clean’ without your cancer rapidly proliferating?

3) What previous treatments deny trial participation?---often, previous chemo, EBRT, or radioisotopes deny trial entry.

4) What disease conditions deny trial participation (bone mets/soft tissue disease, PSA rise/decline)?

5) What happens if you react negatively to the trial agent(s)?---are you summarily dismissed (often, you are dismissed and not even considered as a statistic = you never existed as a participant)?

6) Does the protocol provide for funding of medical care arising from complications associated with the research? What medical care can you expect if you are dismissed for adverse reactions to the trial agent(s) (most consent forms say you are on your own and often, your primary doctor does not have the vaguest idea what to do with you once you have the trial agent(s) in your body)?---Assure that your insurance coverage will respond to any treatments required as a result of the trial agent(s); (many insurance plans deny reimbursement for damage from experimental drugs).

7) Assure that the doctor/investigator who recruits you for a clinical trial is qualified in the practice of medicine specific to the trial.

8) Assure that the doctor/investigator has adequate training in the conduct and ethics of research methods and have him/her satisfy you that the research project protocol and proposed procedure conforms to government regulations.

9) If the recruiting doctor/investigator is also your treating/consulting doctor, assure that a third person (who is not financially involved) reviews the consent form and explains it fully to you before you sign it.

10) Insist that the recruiting doctor/investigator reveals all financial relationships with all parties and commits to the exact financial remuneration for recruitment and the chain of financial relationships with government agencies, drug companies, and private contract research organizations.

This proposed check list seems onerous---but your life depends on your own due diligence in assuring that you understand what to expect from participating in a clinical trial.

Bill Aishman August 2002 blaishman@worldnet.att.net

NOTE: I am not a doctor and can not render medical advice. I am not a medical researcher. I am a prostate cancer patient and I performed this layman’s analysis for my own decision-making purposes. In conjunction with a medical team, every cancer patient must make their own decisions regarding treatment options. I make no claim that this analysis is definitive or complete. I invite any and all additive contributions to my analysis that will provide patients a framework which will enhance their ability to make informed decisions regarding possible entry into cancer clinical trials.

* The Office for Human Research Protection (OHRP) is a result of: the national research Act of 1974 required institutional review boards to approve and monitor all federally funded research; the Department of Health and Human Services complied by creating the OHRP.

REFERENCES

This paper is a compilation of my opinions and my interpretation of :

(1) Morin K et al.; Managing Conflicts of Interest in the Conduct of Clinical Trials; JAMA January 2, 2002, Vol. 287, No. 1:78-84.

(2) Gelijins A, Their SO; Medical Innovation and Institutional Interdependence; ibid.:72-77.

(3) Kalb PE, Kocher KG; Legal Issues in Scientific Research; ibid.:85-91.

(4) Cohen GI; Cancer Clinical Trials: A Primer for Participation of Community Physicians; ASCO 2002 Educational Book; pp. 283-289.

(5) Abrams JS and Cummins C; Implementing Clinical Trials in Your Practice: Getting Started and What’s New; ASCO 2002 Education Book; pp. 273-282.

(6) Time Magazine; New Medical Testing Has Turned Us Into Human Guinea Pigs; 22 April 2002; Medicine Section.

(7) Los Angeles Times; Commentary; Lansing S and Schwarzkopf N; Greater Clinical Trial Participation Is Critical to Fight Cancer; 22 July 2002.

(8) Reuters Medical News; WMA Calls for More Action on Conflict of Interests; 5 April 2002; www.medscape.com/viewarticle/431342_print

(9) CURE; Spring 2002; pp. 50.

(10) New York Times; Eichenwald/Kolata, Drug trials hide conflicts for doctors; May 16, 1999; A1.

(11) New York Times; Eichenwald/Kolata, A doctor’s drug trial turns into fraud; May 17, 1999; A1.

Importance of Clinical Trials

By Maynard Berkowitz

Every procedure, every drug, after testing in test tubes, petri dishes, and on mice, rats, dogs, monkeys, etc. Has to be tested on real live people before it becomes an accepted procedure or approved drug. If no one ever volunteered as a subject in clinical trials, the art of treatment for any disease will be the same tomorrow as it is today. I think that today's treatments are lacking. Who among you wouldn't like to have a pill with less side effects, better outcomes, or perhaps a less invasive or quicker way to cure a disease.

A clinical trial is a research study done to find better ways to prevent, diagnose or treat a disease or condition. It may be done by doctors or researchers.

Usually when someone says clinical trials, they think of cancer. It's true that a good many trials are for cancer, but less than 50% of the clinical trials listed on the NIH web site are related to cancer. There are trials on almost every disease. More about this later.

There are four different types of trials. Treatment trials, prevention trials, screening trials, and quality of life trials.

Treatment trials test new treatments such as a new drug, a new surgical procedure, or new radiation techniques, or even combinations of treatment. This is the kind of trial that most people think about when using the term "Clinical Trials". In this type of trial, it is presumed that the participants have the condition the trial is aimed at. This is the type of trial that I will discuss mostly in this presentation. Other trials are sometimes referred to as Investigations.

Prevention trials test new approaches such as medicines, vitamins, minerals, diet, etc. in an attempt to prevent a certain type of disease or condition. Here it is assumed that the subject is not afflicted with the disease or condition, or perhaps had it, but was cured. Especially for those that are at high risk for the disease or condition. One of the largest trials in the country is the STAR trial. This trial is studying the effect of Tamoxifen and Raloxifene in reducing the incidence of Breast Cancer in post menopausal women, that are at high risk. In addition, it will evaluate the effect of tamoxifen or raloxifene on the incidence of intraductal carcinoma in situ, lobular carcinoma in situ, endometrial cancer, ischemic heart disease, fractures of the hip and spine, or Colles' fractures of the wrist. It will evaluate the toxic effects of these regimens in these patients and determine the effect of these regimens on the quality of life of these patients. This trial is being conducted at over 500 locations, and will eventually enroll 22,000 patients.

Screening trials test the best way to find a particular disease or condition. Obviously, a participant does not have to have the disease or condition at the time of his / her acceptance into the trial. Some do, Some don't.

There are also quality of life trials or supportive care trials that seek better ways to improve comfort or quality of life for affected participants. Some examples might be pain management, or hair growth, or even erectile dysfunction. These trials are not intended to cure a disease or condition, but to improve quality of life.

Most clinical research that involves the testing of a new drug progresses in an orderly series of steps called phases. Clinical trials are usually classified into one of three phases.

Phase I trials evaluate how best to administer the drug, such as Intravenous or intramuscular or perhaps by ingestion. To determine the safe dose, and how often it is given. These trials are sometimes referred to as dose escalation trials. An eye is kept on the safety of the drug to determine any gross problems, and what the side effects are. Usually the patients in Phase I trials are very closely monitored. After all, these patients are the very first humans to get this drug or treatment. Phase I trials are usually quite small, and may enroll as few as a dozen and seldom exceeds 100 people. These trials are usually the most risky.

Phase II trials continue to test the safety of the drug or procedure and starts to evaluate how well the new drug works. These trials typically involve a larger number of participants and there may be 50 to 500 patients. Usually, these II trials are safer than Phase I trials. They already know how to administer the drug, and they know what dose to give, and they have a good handle on most of the gross side effects.

Phase III studies, assess the value of the test drug against a placebo and/or approved therapy. The FDA likes these studies to be widespread geographically, and enroll numbers of patients that will yield unequivocal, statistically valid results. This is the all important phase that takes the studies from a few academic sites [usually], where the appropriate dosage/ use has already been determined, and now has to be transferred to 'real world' clinical usage. It is the step that precedes final approval to market the drug. Phase III trials involve a larger number of patients, and may have thousands enrolled in the trial.

Occasionally, two phases may be combined such as a trial that is both Phase I and Phase II. In these cases, the objectives of both phases are looked at simultaneously.

Sometimes a drug for treatment of a particular condition had a side effect that seems to affect some other condition far afield from it's original intended use. One such drug is Finasteride (Proscar). Finasteride is used as a cancer treatment drug, and one of its side effects was that it seemed to increase hair growth. The drug was again tested in a clinical trial. It is now marketed under the name Propecia. Some might ask, word would get around, and since it could be prescribed off-label, why bother? The answer is there is a distinct advantage in being able to advertise it on TV to the general public.

There are studies that are post marketing, and are meant to monitor for additional safety data and clinical use, requiring no comparison to other drugs or placebos. These are called Phase 4. The drug is approved, and in usage. It usually enrolls no patients, and all those taking the drug are potential participants and they seldom know that they are taking part in such a trial. Sometimes doctors take part of these post-marketing trials, and are usually paid for their effort in the extra paperwork required. If a problem arises, and it is deemed serious enough, the drug or treatment could be withdrawn. This happened recently when Rezulin, used for Type II diabetes, that was non responsive to insulin, was recalled because some users of Rezulin suffered liver damage.

In the time period 1976 to 1978, there were 174 clinical investigational New Drug Applications (NDA's) filed with the FDA. Of these, 150 (86%) made it to Phase I trials, and 124 (71%) made it to Phase II trials, and only 56 (32%) entered Phase III, only 35 (20%) made it to become approved drugs. The largest failure rate seems to be between Phase II and Phase III with less than 50% of those entering Phase II making it to Phase III. The reasons for this drop out rate are varied. It may be that the drug did not show as much activity as they expected. Perhaps the manufacturer is pursuing many potential drugs and doesn't have the capital to continue all of them, and they are putting their emphasis into one or two drugs that have the most promise (read most profit potential).

Most recently, a drug named Uprima was thought that it would give Viagra some competition was pulled off of trials because of side effects. Usually, unless you were involved in the study, you would never even know that a drug had failed.

Many trials are sponsored by the drug industry, and they won't sponsor a trial that will not yield a significant return on their investment. For example, no company would sponsor a trial on the use of Aspirin, since it is so cheap, and no company owns the rights to it. Any benefit aspirin might provide would not give the sponsoring company any additional profit, or even pay for the cost of a study. However, Universities and the Government will sponsor such trials. Aspirin is touted as an excellent immediate first treatment for heart attacks. This was found out not by drug companies, but by NIH sponsored trials. At the present time there are two trials on the use of aspirin, both sponsored by research organizations.

Clinical trials can be very expensive, sometimes costing over 100 Million dollars for just one trial. Pharmaceutical companies expenditure drowns out that spent by the federal government for clinical trials.

What the Government spends for research in cancer is a very small amount compared to that spent by pharmaceutical companies with a hope of recovering some of the costs of drug development.

From Robert Finn's book: "Cancer Clinical Trials" a good book and I recommend it highly, for those interested in clinical trials: "According to Ken Getz, president of CenterWatch, which publishes newsletters for the clinical trials industry, current estimates indicate that it will cost an average of 500 million dollars to develop each successful new drug entering research and development in 1998. For drugs coming to market now, the average development cost was 289 million dollars. It takes twelve to fifteen years for a drug to make it through the pipeline from discovery, through preclinical development, through clinical trials, through the FDA approval process, to market. These figures include the amortized cost of unsuccessful drugs that never make it market, but they do not include post-market costs, such as advertising and marketing."

Time is also very critical in drug development. The time required for a drug to go from Phase I to the time it reaches the pharmacist shelf could exceed 7 years. During this time, a drug company runs the risk of having another company come up with a competing drug that is just as good, or even better. In addition, the clock of exclusive patent protection is running, and any additional time added to clinical trials subtracts from the time of having the patent protection as an approved drug.

Every clinical trial has a document called an informed consent document. This document lists, in detail, the purpose of the study, the procedures that the patient must undergo, risks, benefits, costs, and a contact person. This document must be reviewed with the patient by the doctor or the investigator, in detail. At this time, the patient has the ability to ask questions, and go over the procedures. To participate, it must be signed by the patient. This is done even before qualifying tests are conducted.

The question of whether a particular person should participate in a trial is up to the person himself. Only he can make that decision.

The patient should study the consent form and make a decision about whether to join the study or not. He should be guided by his physician.

Some of the benefits of a study are that the patient may receive a type of treatment that is not generally available. He or she may have their condition more closely monitored than if they were not on a trial.

On the down side, it is possible that the treatment may not improve the patients' condition. In addition, it may result in a worsening of the condition, or perhaps a delay in getting recognized treatment.

After all, if we knew that the trial treatment would be better than standard treatment, we would not have to test it. We expect that it might be, but we really don't know.

Usually, the trial sponsor will pay the costs associated with the trial drug or procedure. However, in most cases, there are some costs associated with participation that are not paid, such as tests to determine the patients progress, and either the patient or his insurance company will be billed. This will all be spelled out in the consent form. Sometimes, these costs will exceed the cost to patients of using standard treatment. Some trials will actually pay the participant, or perhaps reimburse them for expenses.

Trials held at the NIH hospital in Bethesda, Maryland will not pay for participation, but they may reimburse participants for travel expenses, and room and board during their treatment. This means that the first visit is on the patient, but once he enters the trial, he may be eligible for reimbursement.

On June 17th, President Clinton issued an executive memorandum directing Medicare to revise its payment policy and immediately reimburse providers for the cost of routine patient care associated with participation in clinical trials. How this will affect what was said about costs that patients might have to pay is unknown. It seems that for those patients on Medicare, they would not have to pay anything except their own travel expenses, and Medicare's standard deductible.

In any case, if the patient determines that his participation in the trial is not in his best interests, or even for no reason at all, he may terminate his participation at any time. In these cases, it may be difficult for a patient to get on a clinical trial in the future. In addition, the investigator or sponsoring company may terminate the patient's participation.

There are thousands of clinical trials being conducted. The NIH lists 3975 trials at this time. While the National Cancer Institute list 1775 trials for cancer. There are trials for other agencies such as the CDC. And these are just those trials that are government sponsored.

Most people that qualify for these trials do not partake of them. Perhaps travel is a consideration, cost or even fear that they don't want to be guinea pigs, they don't want to be harmed, for whatever reason, about 3% of those that would qualify for a trial actually volunteer, and among seniors, it's about 1%. This lack of volunteers translates into a delay in approving new treatments. It also contributes to an increased cost of drug development. And people are dying that could be saved, if new drugs were available. In the 1950's, extending into the 1970's, and perhaps even into the 1980's, almost 99% of the children being treated for cancer were on clinical trials. Even today, this number is high, with about 75% enrolled in clinical trials.

No, not every patient you treat should be on a clinical trial. But, when a patient presents with a worsening condition in spite of getting the best treatment available, he should be informed about a clinical trial that could conceivably be of some benefit to him.

Much of the blame for a lack of volunteers for clinical trials must be laid on the medical community. You cannot expect patients to know what clinical trials are available, and even if they did know, how would they know which trials they might qualify for, or which trials might benefit them.

You as doctors should let patients know if they qualify for a trial, and if the trial will be of any potential benefit to them, and refer them to the researcher doing the trial. Not for every patient you see, but certainly for those that you expect will have a less than desirable outcome.

In a small hospital like Carson Tahoe Hospital, not associated with a teaching institution, there are no trials that are going on at this time. And some patients would probably balk at having to go somewhere like Bethesda, Maryland for treatment, and follow up exams. Some trials may allow the patient to go to them for the initial treatment, and have follow up treatment or follow up monitoring done at a patients local doctors office or hospital. Perhaps the patient may have to go to the main treatment center once every six months, or maybe once a year.

This is not mentioned in the consent form, and should be worked out with the principal investigator prior to applying for admission to the study.

There are some 10 cooperative research groups. These are institutions and investigators organized for the purpose of improving the survival of patients through clinical research. They make it easier to conduct multi-center trials. Some of these include Cancer and Leukemia Group B(CALGB), South West Oncology Group (SWOG), and others that coordinate research among their members.