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BMJ. 2007 September 8; 335(7618): 478.
PMCID: PMC1971171
Head to Head

Should terminally ill patients have the right to take drugs that pass phase I testing? Yes

Emil J Freireich, professor

The United States is considering allowing experimental drugs to be given to people at the end of life. Emil J Freireich believes patients should be able to judge the risks for themselves, and Dean Gesme counters that use of such drugs outside trials will damage both individuals and science

Around half a million people will die from cancer related causes in the United States this year. In the US, as in much of the Western world, patients know their diagnosis and are often given a hopeless prognosis. For most, the option of participating in phase I and phase II clinical trials of new drugs that offer some promise helps them remain optimistic. Clearly, they should have the right to take drugs that have passed phase I testing.

The problem is that most cancer patients cannot participate in phase II trials because they are either ineligible or they are unable to fulfil the financial and social requirements for participating in such trials, such as staying in the centres conducting these trials, sometimes for many weeks or months. The problem is clearly not one of safety because these drugs have completed phase I clinical trials and there is sufficient information about them to justify a phase II trial to determine efficacy.

Phase II trials are designed to give the highest probability of a positive outcome. Thus, they have patient eligibility requirements which assure that only the healthiest patients at the earliest point in their disease are entered. These decisions are not based on any reasonable evidence that patients who are ineligible would not benefit, but are strictly designed to fulfil the regulatory requirements established by bodies such as the Federal Drug Administration (FDA) and the regulatory components of industry and academia that govern these clinical trials.1 2

Compassionate prescribing

In the modern electronic era, most of the patients with hopeless cancer diagnoses have access through the media and the internet to information about promising new drugs that are in phase II clinical trials. These patients would like very much to receive these drugs to offer them some hope, but for the reasons mentioned above are unable to participate in those trials. So why not offer these drugs to these patients on a compassionate basis?

The first reason given is usually the safety concerns. Without knowledge about how renal function, cardiac function, age, etc affect the action of the phase I drug, side effects might occur that could be harmful to the patient or, perhaps more importantly, the continued development of the drug. I think this objection is relatively minor since it simply states the benefit:risk ratio problem—that is, these patients are prepared to volunteer to expose themselves to increased risk because of their hopeless prognosis and because of the promise of the new drug.

The second objection is that it will interfere with the development of the drug. However, in the past, the FDA and the National Cancer Institute have allowed compassionate use of drugs and have found that it actually accelerates development. This is because when patients are offered compassionate use of an experimental drug, their doctors have to collect information as systematically as in the research protocol and submit it to the sponsor. Information is therefore available about use of the drug outside trial conditions. For example, if patients with impaired renal function not only tolerate the drug but respond, it will assist in drug development to have that knowledge collected systematically.

Another objection is that the drug industry might use this device to profit from investigation of a phase I drug. I believe this is a trivial objection because the usual strategy for compassionate use is that the drug is provided at cost. The last, and perhaps the most serious, objection is that expanded access would interfere with the clinical trial process. This certainly should not be the case. The clinical trial process is governed by the regulatory bodies in government, in industry, and in academic institutions. The unfortunate consequence of this is that physician scientists, who have the most experience, the most training, the most knowledge, the most productivity, and the most creativity, are completely excluded from this process. Because of the relationship between the regulatory organisations of government, industry, and academia, the academic physician scientist can only implement protocols that have been developed by the drug developer with direction from the regulatory agencies. Expanded access would bring the doctors back into the drug development process and, rather than damage the clinical trial system, would greatly expand its effectiveness and value.

In summary, patients with advanced cancer and limited life expectancy should have the same privilege as all individuals in a free society—that is, to decide their own benefit:risk ratio. It is tragic that regulatory bodies have created a circumstance where people have to live in an aura of hopelessness even though they have the will, the resources, and the ability to expose themselves to the risk of participating in investigational studies and to enjoy the potential for benefit. The solution is legislation or judicial action to permit expanded access to experimental treatments for patients with limited life expectancy.3 4

Notes

Competing interests: None declared.

References

1. DeVita VT. Should the FDA be the doctor of last resort? Nat Clin Pract Oncol 2005;2:423. [PubMed]
2. Seeber S, Braun AH. Phase III trials in oncology: setting standards of care? Nat Clin Pract Oncol 2005;2:426-7. [PubMed]
3. Freireich EJ. The investigational new drug application—who benefits? Nat Clin Pract Oncol 2006;3:62-3. [PubMed]
4. Abigail Alliance for Better Access to Developmental Drugs. .www.Abigail-Alliance.org

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