3) Sick Humans

Consent

The consent of patient to a therapy or any research must fulfill three different requirements in order to be considered acceptable. It has to be a voluntary action of the patient,the subject of the study must be competent to make such decision and the patient must be properly informed about what the trial entails. Even though all of these principles ensure the ethicality of the patient's consent for a clinical trial, their execution can be problematic.

The ability of the patient to decide whether is in their interest to participate in a trial is questionable in some cases, specially in patients that are seriously ill and have tried all conventional treatments. In these cases it can be argued that the subject is not in a right mental state to  decide. As the circumstances put them in a desperate state of mind,in which the experimental treatment can be presented as their only hope. Closely related to this point is the fact that the patients need to be able to make an informed decision,the application of this principle is often put to question because of the difficulty in determining which is a valid amount of information to accept the consent. The information that a patient needs to make an informed decision is generally thought to include:

1) An understanding of the risks and benefits that the treatment entails for the patient

2) Comprehension of the procedures that the patient may undergo and the awareness of the purpose of the research.

Despite of the possibility that the patients enrolling trials might have a therapeutic benefit during their participation in the trial, that is not the primary objective of the trial and the small odds of a recovery of improvement in their conditions may not be fully disclosed. Leading to the patient to believe that the trials are seeking their benefit is what is called therapeutic misconception in which medical investigators try always to run their experiment with a therapeutic goal. Ambiguity in the odds for improvement in the patients is another major issues specially when seriously ill patients participate in phase I clinical trials where the objective of the trial is to determine if the drug is safe or what side effects it may cause.

Informed Consent [10]

HMS Salisbury - No Risk No Reward?

One of the first clinical researches performed are believed to be aboard the British Royal Navy ship the HMS Salisbury in 1747 conducted by James Lind, the ship’s surgeon. Lind believed that some of the medical interventions such as sea water and vinegar being used to treat scurvy on the ship was having negative effects on the sailors conditions. Scurvy is a disease resulting from a lack of vitamin C which causes variety of symptoms ranging from weakness to gum disease, which can also eventually lead to death. Unlike other doctors in that time period, he did not assume whatever he was told was correct and thus decided to do a medical trial of his own. He divided a hand selected group of 12 sick sailors into 6 groups of 2 and assigned a different medical intervention to each group including feeding 2 oranges and 1 lemon each day to one of the groups and sea water to another. The group that received the orange diet had a full recovery in a week while the sea water group was dying. Using his findings, James Lind was able to save almost all the sailors on board his ship.

The Royal Navy did not adopt Lind’s medical findings as they believed it to be ridiculous for another 50 years. Once the Royal Navy adopted citrus rations, scurvy virtually disappeared. Scurvy is not well know any more because we are able to prevent it due to James Lind’s findings. However, if he did not conduct his medical experiments on these sick individuals, millions of more people could have died. 

HMS Salisbury [12]

Clinical Equipoise

Clinical Equipoise is the assumption that there is no better intervention present than the one that is currently being used. An equipoise exists when there is no good basis between two or more treatment options for a patient. Personal equipoise is when the doctor or clinical treatment provider has no personal preference as to which treatment may be a better option for the patient. [6] For clinical trails, it must be the case that there are no treatments available outside the trial that are better than those used in the trial. Satisfaction of these conditions seems to imply that the interests of research subjects will not be undermined in the service of collecting scientific information. If the available data do not favor any of the treatments being used, randomizing subjects (discussed later) seems as good a process as any other for choosing which treatment they receive.

Although clinical Equipoise sounds good on paper, it could constitute therapeutic misconception concerning the ethics of clinical trials. Therapeutic Misconception is the mistaken impression held by patients enrolled in medical research trials that the research in which they are participating is most beneficial to them personally or is their last best hope of a cure. It is sometimes hard to present all possible treatment options to a patient as there are many factors that can affect their treatment. Patients with a “last chance of survival” mindset are a lot easier to convince to take a non conventional approaches even if it has a smaller chance of recovery then other treatment options. This is why Clinical Equipoise is a concern as patients believe that they are getting the best treatment option possible for their specific case, and usually such clinical studies do not take personal details into account. An example of this would be where a specific patient may have reduced liver function which places her at greater risk of harm if she receives a treatment metabolized by the liver [7]

Clinical Equipoise [13]

Randomization

As mentioned before, in phase 1 of clinical trials, a drug is first tested in a laboratory to see if it meets basic medical safety standards. This early stage study is also called a preclinical trial and is where you learn what dosage to give to people and its side effects. Typically this phase is tested on healthy people. A drug is phase 2 of clinical trials means that it has already met basic safety standards. It is used to test the new drug in a larger group of people to evaluate the effectiveness of the drug for a particular disease. These trials usually involve 100-300 volunteers of both healthy and sick people. Phase 3 is usually a more large and complex phase. It usually involves multiple large groups that used to compare the drug to other treatments. In phase 3, usually a process called Randomization is applied for patients receiving the treatment. [8]

Randomization is a process in which patients are assigned to groups that receive different treatments. The unbiased process of assigning patients to treatments is called Randomization. Bias could occur when patient treatments are affected by human choice. For example, a doctor could assign his patients which he believes will likely be treated better with one treatment option, sometimes without even meaning to. This sort of bias could affect the trial results and Randomization ensures that this does not happen.  

If you are planning to join a clinical trial that includes Randomization, it is important that you understand these things. The best possible treatment option for your case might not be the one that is also selected for you during this trial. This is because most randomization is done via computer not on clinical judgement. [9]

The downfall of Randomization is that it appears to sacrifice the interests of subjects in order to collect valid data.  Patients should not be denied any other beneficial treatments that could help their case, just to insure the experimental results are not skewed. However this is not always the case because it can get overlooked in these experimental scenarios. It is not acceptable for a doctor to participate in a clinical trial unless it is consistent with the patient’s medical interests. [9]

Randomization [9]