Survey

Context and method

Working on a treatment by genetically engineered bacteria, we thought absolutely necessary to consult the hemochromatosis patients. Our survey aimed to give us an idea of how these patients perceive their disease, of what they could need, and if our treatment was an appropriate response.
We created an online survey, and we send it to the French associations of patients, and they respond massively. In France, there are 200 millions of people who have the mutation C282Y on HFE gene. However, the number of persons who develop symptoms of Hemochromatosis is low; The exact number of patients in France is unknown. There is about 3000 patients in the French associations and we have collected 270 answers.
Thus our survey is significant and representative of the French hemochromatosis patients.

In addition, we tried to consult English speaking patients, but we had too few answers to use them.

Nonetheless, before presenting the results, we must highlight some of the methodological flaws of the survey.
The patients are members of an association, so they could be more aware of the medical and scientific aspects of their disease than average patient: in other words they may be more probably expert patients. On the other hand, as hemochromatosis is a (rare) genetic disease, the difference between average patients and members of patients’ associations must be less important, because they all had to understand an unusual disease.
The patients are (mostly) not thalassemia patients, what means that they can be treated by bloodletting.
On the advice of one of our advisors, we did not explicitely tell that the bacteria was genetically modified. This choice was due to the strong distrust of the French society against GMOs: we feared that the patients could be negatively prejudice against our treatment, and we tried to obtain from them a more neutral point of view. This obviously modifies some of the responses, for example it probably reduces the fears, increases the will to test the treatment, and it makes the questions concerning the safety of others and the safety of environment unusable. Retrospectively this may have been a methological mistake: we should have neutraly explained how we changed the bacteria in order to get the informed point of view of the patients. Ideally, we should have done to parallel surveys, one using “modified bacteria”, the other using “genetically modified bacteria”, in order to mesure if the fear of GMOs plays a role in the patients’ perceptions. As we could not do it, we must keep in mind this uncertainty.

General results

Some unsurprising results

Significant rates of “no opinion expressed”

Concerning the questions about the bacterial treatment, a significant number of patients did not give any opinion. This reflects their difficulty to answer in situation of incertainty, and the caution due to the lack of information they were given: these explainations are confirmed in the remarks that the patients were free to formulate about our treatment. Far from being a problem for our survey, this points out the seriousness and implication of the patients that have answered our survey. It strengthens also the clearly expressed opinions: we can think that they are cautiously given.

A paradox

The most obvious result of the survey is a paradoxical: hemochromatosis patients are mostly satisfied of their present treatment, nonetheless they wish for a complementary treatment.
75% of the patients find their treatment effective, 57% do not complain about major trouble due to their disease. Thus 76% declare to be rather or quite satisfied of their treatment. In parallel 38% of the patients would be ready to take part in the clinical testing phase of the bacterial treatment: knowing that 67% of them declare that they fear ingesting a modified bacteria, it is a high number of volunteer. Moreover, 45% think that is is no ordinary treatment (38% think that it is). Last but not least, if it was authorized by a national agency, 56% of the patient would be willing to take this treatment (19% would not and 25% did not give any opinion).

The survey and the iGEM Iron Coli Project

Thus hemochromatosis patients do not objectively need a new treatment, because bloodletting is efficient, moreover they fear modified bacterais, and nevertheless we found a strong support for our potential treatment. Explaining this paradox is difficult, and this difficulty forced the team to rethink the strategy several times.
The first hypothesis of the team was that hemochromatosis patients would be unsatisfied with a treatment by bloodletting. That is why we tried to create a biosynthetic treatment in the first place. When we asked specialists and presidents of patients associations, we found out that bloodletting was a satisfactory treatment. Knowing the collective mistrust against genetical modifications in France, we thought that the survey would show at least uninterested patients, and more probably a reject of our potentiel bacterial treatment. We were partially right, because, even if we did not explicitely said that our treatment was genetically engineered, we have found a fear from the patient. But we have also find out that they had a real interest in our treatment.

In-depth analysis

The results will be analysed according two aspects: first the age of the patient, and then the time since the diagnosis. Our hypothesis is that life styles, life expectancy and hemochromatosis experience have an influence on how the patients perceive an alternative treatment.

Age categories

We separated the patients in three categories of age: people who are under 36 years old, people who are between 36 and 60 years old, and people who are over 60 years old.
People who are under 36 years old are young and thus will live with hemochromatosis for a long time. Moreover we suppose that they were diagnosed before the symptomatic phase of the disease, and thus have less health problems due to the disease, and maybe also a less heavy treatment.
Middle-aged people present a great variety of profiles: there are people with an already long experience of the disease and its treatment, others who just discovered it because they entered the symptomatic phase and who are still in the heavy first phase of the treatment, and there are all the intermediate situations.
People other 60 years old are most likely patients used to the disease and to the treatment. If they are retired they have more time, that is essential because blood-letting takes time and requires rest. This probably induces a different point of view on the disease. Of course these categories are statistical, that means they can not be homogeneous, they only help us to interpret our results.

We observe a clear difference of attitude concerning the clinical testing phase from the middle-aged patients. Unlike the other categories, the patients ready to participate to the testing phase are more numerous than those against. It must be noted that all three categories present almost the same significant number of “no opinion expressed”. Thus the middle-aged category presents proportions exactly inverted.

One explaination would be that the patients under 36 years old do not want to take a risk even if they think that a bacterial treatment would be beneficial, and that the older patients do not see an improvement sufficient to take the risk. Moreover a clinical testing is rather binding. On the contrary, middle-aged patients may perceive the advantage it would be to use both treatment strategies to improve their health state.
The patients over 60 years old are also less interested in the bacterial treatment if it is authorized by the national agency for drug safety (ANSM). Only 40% of them are interested against 60% in the two other categories. In all three categories, around 20% of the patients say to be uninterested by the treatment. Thus the patients over 60 years old are more numerous to be doubtful or without opinion.
We may suppose that this category of patients really does not see a major interest in the treatment, because we observe that they are less afraid of the treatment than the two other categories of patients. Indeed, the fear of a genetically engineered bacterial treatment decreases as the age of the patients increases (we must remain careful about this, because it can be due only to the fact that younger people understood more easily the implicit role of genetic modification).
This observation is particularly interesting, because it means that fear and interest in the treatment are not linked: the patients under 36 years old are the most worried about the risk, but they are also predominantly interested in taking the bacterial treatment.

Thus we can conclude that being worried about the risk is not deciding concerning the interest in the treatment, and this is more likely linked to the potential improvement it may give. It seems that people in age of employement are more aware of this potentiality. This can be explained by the side effects of bloodletting on time and energy.

Living with the treatment

We also separated the patients according to the time since their diagnosis: between 0 and 2 years since the diagnosis, between 3 and 10 years since the diagnosis, and over 10 years since the diagnosis. The first category of patients is characterized by the discovery of the disease, by the beginning of the treatment that can be very heavy, and by the necessity to learn to lie with all this. The third category of patients can be said to be used to the disease and the treatment. The intermediate category of patients is probably far more heterogeneous, and thus more difficult to interpret.

This categorisation makes very clear that the recently diagnosed patients are far more willing to participate to the clinical test phase than the others (more than 50% of them against around 30% for the two other categories). This can be partially explained by the fact that these recently diagnosed patients are also less satisfied or more doubtful about their treatment than the other categories of patients. But it does not explain everything, because they still are 60% to be satisfied with their treatment. Thus the difference could come from the fact that the recently diagnosed patients want to do everything they can to fight their disease. When they are used to it, patients seems to be less interested by an alternative treatment. This is confirmed by the fact that the longer the patients know their disease, the less they wish to take the bacterian treatment if it is allowed by the national agency for drug safety. The other results are almost the same from one category to the other.

A hope for substitution treatment

The survey confirmed an intuition: the more the patients are satisfied with bloodletting treatment, the less they are interested in another treatment. We can see an almost linear correlation between the satisfaction with bloodletting and the wish to take the bacterian treatment if allowed by the national agency for drug safety.
Keeping in mind that people unsatisfied with their treatment are far less numerous, we observe that they are far more willing to participate to the clinical testing phase. The patients who declare to be completely unsatisfied are unsurprisingly massively ready to test this treatment.

Conclusion

We learned three important informations with our survey.
Most patients are satisfied with bloodletting, and the more satisfied they are, the less they want another treatment. Despite this, they remain interested in a complementary treatment.
The most interested patients are the patients who would benefit the less from the bacterian treatment. Indeed this treatment would be most appropriate after the first phase of treatment, to help regulating iron absorption and diminishing the frequence of bloodletting.
Last but not least, our survey shows that a bacterian treatment would be a real help for working patients, who often have difficulties to leave their job to go to bloodletting.