Can medications be used pending regulatory approval or ‘off label’ for · Medical

10 Can medications be used pending regulatory approval or ‘off label’ for non-licensed indications to save the lives of military personnel?

Step 1 – IDENTIFY THE PROBLEM(S)

• Briefly state the Scenario

Can medications be used pending regulatory approval or ‘off-label’ for non-licensed medications to save the lives of military personnel?

• List the Issues that arise from the scenario

The balance of wanting to help the patient with their condition by prescribing a drug, but the risk of doing harm by giving a drug that may have risks alluded to the fact that it has not been formally approved by the MHRA.

• Identify Critical Information required and Assumptions to be made

Step 2 – ANALYSE

Patient: What are the views of the Patient? (and ‘patient group’)? How do 4 principles of : Autonomy, Beneficence, Non-maleficence and Justice apply? Other perspectives?

In the case where a drug has been given off-label to a patient, informed consent must be given.

Clinical: What are the clinical diagnosis, prognosis, treatment options? Is this scenario covered by professional regulation or guidance? What are the views of individual members of the clinical team? Other perspectives?

The baseline of acceptable clinical practice is a doctor thinking in terms of a patient’s best interests.

And also balancing providing quality care with unique challenges of limited resources and instability of working in military environment.

Variations in clinical practice with the same patients but in different scenarios/resources/environments is acceptable. However this must be justified.

Pre-established standards of procedure can help minimize too much discrepancy in clinical practice.

Legal: Is scenario covered by IHL, Geneva Conventions, military law, other law? Other perspectives?

Off-label drug are drugs that have not been formally approved by the regulatory body for medicines in the UK which is the Medicines and Healthcare products Regulatory Agency (MHRA).

It is acceptable under specific conditions in military healthcare circumstances. This includes for populations not covered by regulatory trials such as children. Or when the benefit of treatment in emergency scenario in military environment outweighs the potential risk of giving the drug, that may or may not be the reason that drug has not been formally approved by the MHRA. This could be due to no alternatives due to limited resources in a military environment. Informed consent by the patient must be given in these scenarios.

Medical experimentation is allowed but with strict oversight.

The experimentation must be approved by regulatory bodies such as UK Ministry of Defence Research Ethics Committee (MODREC). Research plan is reviewed and third parties such as International Committee of Red Cross may observe and audit research to ensure that it complies with standards.

Societal/Military: Is there a military necessity? Is this scenario covered by military regulation or military perspective? Is this scenario covered by public health or societal ethics? Other perspectives?

There have been medical innovations that have been driven through military necessity, such as vaccines against typhoid and influenza that were prevalent in military environments.

Blood transfusions and also use of Factor VIII for coagulopathy emerged out of need to provide immediate care to soldiers on the battlefield.

Analgesics and antibiotics were also driven out of military necessity.

These all emerged because the conditions that were being treated whether infectious or trauma related were happening on a large scale in military environments.

An example where human experimentation in military healthcare has been done unethically is Tuskegee Syphilis Study. The study aimed to observe the natural progression of untreated syphilis in African American men, under the guise of providing free healthcare. 400 participants were falsely told they were being treated for "bad blood," a local term encompassing various ailments. In reality, they received no effective treatment for syphilis. Even after penicillin became the standard treatment for syphilis in 1947, the researchers deliberately withheld treatment to continue observing the disease's progression.

Military oversight bodies differ from civilian oversight bodies in that they approve research from a greater focus on military demands. Civilian oversight bodies approve research from the perspective of the individuals involved and the risk to them. International oversight bodies ensure that the research is compliant with international standards.

Step 3 – FUSE

· Summarise conclusions

· Insert citations to key reference sources for your analysis

· Determine the exact Decision(s) to be made

Off-label drug use in military healthcare is acceptable under strict conditions, such as for populations not covered by trials or emergencies where benefits outweigh risks. Informed consent is crucial. Medical experimentation is allowed with regulatory approval, oversight by MODREC, and audits by bodies like the ICRC. Clinicians must balance patient interests with military constraints, adhering to professional standards. Variations in practice are justified by context but must follow pre-established protocols. Military necessity has driven innovations like vaccines, blood transfusions, and antibiotics. However, unethical experiments, such as the Tuskegee Syphilis Study, highlight the need for strict oversight by military, civilian, and international bodies.

Step 4 – DECIDE

• What is your Decision?

• Why (can you justify it)?

• Residual uncertainly, need for review?

Off-label drug use in military healthcare is allowed with informed consent in emergencies or unique populations, overseen by MODREC and international audits. Clinicians balance patient care with operational constraints, adhering to ethical standards. Military necessity has driven innovations like vaccines and blood transfusions but underscores the need for strict oversight to avoid unethical practices like Tuskegee.

Reviewed and formatted by: Yvonne Zhou MBBS Year 3 King’s College London Dec 2024