Population Health

1.0 Introduction

1.1 Description of media report
‘Faeces cure for deadly bug’ is a media report from an online newspaper article, The Sydney Morning Herald which was published on 18th January 2013. The article is about a more effective way in treating Clostridium difficile infection compared to taking antibiotics which is by transplanting healthy human faeces into the patients that are affected by the condition using a colonoscopy or a nasal tube. The aim of the treatment is to replace the healthy bacterias in the digestive tract of the patient. However, the research was discontinued as the ethics committee deems it is unethical to withhold the transplant for some of the patients. Other challenges in the development of this treatment is to find a more pleasant method of administering the donors’ faeces, to search for appropriate donors and lastly, to study and analyse the different types of bacteria present that may cause a complication to the recipient.

1.2 Description of journal article
The title of the journal article is ‘Duodenal Infusion of Donor Faeces for Recurrent Clostridium difficile’ which is published in The New England Journal of Medicine on 16th January 2013. The main purpose of the study was to test the effectiveness of faecal microbiota transplant (FMT) in treating recurrent C. difficile infection. The study was done at the Academic Medical Center in Amsterdam which involved 43 patients who are of adult age (18 years and above), had a life expectancy of at least 3 months and had a relapse of C.difficile infection after at least one course of antibiotic therapy. The experiment started in January 2008 and was stopped in April 2010 after an interim efficacy analysis was performed.

2.0 Media Report

2.1 Purpose of the report
The journalist wrote the media report on faecal microbiota transplantation because of the unique modality of treatment and the almost complete cure for a condition which is severely debilitating and fatal to the patient. Many people are affected by the bacteria, Clostridium difficile, which can infect the bowel system, causing diarrhoea and death. Besides, current antibiotic treatments are not as effective in treating the disease. The tone of the report is clear and concise. It is a factual article and does not have any advertising content, sponsorship nor vested interest in promoting the claim. However, the report is bias towards the positive effect of FMT as it has no mentions of the adverse effect of the treatment. It does have a shock value as it makes an interesting reading material.

2.2 Main message of the report
The main message of the media report is that there is a new hope in treatment for patients who have Clostridium difficile infection which is better and more effective compared to taking antibiotics, specifically vancomycin. However, the method of delivering the treatment is unpleasant but there might be a better option to infused the healthy bacteria in donor’s faeces into the patient in the near future. The patient will also be aware about the peril of the disease as the number of people who are affected by it is high in the United States but is unclear as the disease is not commonly tested for.

2.3 Targeted patient group
This report would attract the interest from those who are at a high risk of getting the infection such as the elderly, those who are on frequent administration of antibiotics, those who are immunosuppressed, patients who have a nasogastric tube or who undergoing non-surgical gastrointestinal procedures, and those who are staying in the intensive care unit (ICU). This is because the issue is related to them and the article shows other options that are available to treat the disease as the current treatment is only 30% effective whereas this treatment is almost completely effective. Apart from that, medical doctors and personnel will also be keen on it to keep themselves updated on the advancement of medical technology.

3.0 Medical Journal Article:

3.1 Research question
The research question being tested in the study is the effectiveness of infusion of faeces from healthy donors into the duodenum of patients with recurrent C. difficile infection. The null hypothesis of this research study is that there is no difference in the rate of cure of C. difficile infection in patients who undergo infusion of faeces from healthy donors compared to those who only take vancomycin with or without bowel lavage. On the other hand, the alternative hypothesis is infusion of faeces from healthy donors is more effective in treating C. difficile infection compared to those who are on an antibiotic regimen with or without bowel lavage.

3.2 Type of study design and methodology
Open-label randomised controlled trial (RCT) is the type of study design used in the research on which the medical journal article is based. The participants of the study was divided into three groups, each receiving a different treatment. Firstly, an initial antibiotic regimen with bowel lavage and faecal microbiota transplant (FMT). Next, the standard antibiotic regimen and lastly the standard antibiotic regime with bowel lavage. A patient is considered cure if there is cessation of diarrhoea caused by C. difficile infection without relapse after 10 weeks.

3.3 Is the study design appropriate?
This study design is appropriate because a RCT is an experimental study design which enables the investigator to control the exposure that affect the result of the experiment. In this case, the factor that is manipulated is the treatment that is given to the patients to test the effectiveness of the different treatments in treating C. difficile infections. There is also a control group which enables the investigator to compare the effect of the exposure on the patient. Hence, it is possible to state that there is a direct causal relationship between the cause and the effect. Apart from that, RCT helps to reduce selection bias by randomly assigning patients to a treatment and detection bias by using a blinded adjudication committee to decide which patients are cured.

3.4 Weakness of the study design
The weakness of this study design is that the result of the experiment might not always represent the population in real life treatment situation even though it has a high internal validity. The limited external validity may be due to the exclusion criteria which excludes patient who are immunocompromised, pregnant, critically ill and admitted to the ICU and those who are taking additional antibiotics to treat other infections. This decreases the sample size of the study and compromise the study’s generalizability. For instance, in this study, 102 patients were assessed for eligibility but only 43 patients were included in the research.

There is also a risk of loss to follow up (LTFU) due to the long study period. In the study, one patient were excluded from the analysis as he is taking a high dose of prednisolone because of a rapid decrease in renal graft function. This reduces the power of the study as fewer subjects can provide the data for analysis.

There is also bias in this RCT as it is open labelled so all the participants of the study knew beforehand the treatment that they are given so the data collected might affected. However, blinding is difficult to perform as the patient will know whether FMT is performed on themselves or not. Thus, the result of the study may be bias towards the beneficial effects of the treatment.

The efficacy of vancomcycin is lower than normal as many of the patients have more than one relapse and are treated using antibiotics. Thus, the results have to be adjusted as the efficacy of antibiotic on patient with only one relapse is higher compared to those with multiple relapses.

3.5 Alternative study design
A prospective cohort study can be done to investigate the research question. Firstly, individuals who are already undergoing the treatment are chosen. Then, the researcher will periodically follow up on the patient and determine who is cured and those who are still sick. Based on the data collected, the relative risk (RR) can be calculated. If the RR is equals to one, the null hypothesis is accepted while the alternative hypothesis is rejected. This study is weaker than RCT because confounding factors can affect the RR calculation and produce an inaccurate result. Cohort study does not have control of the variables that affect the outcome as it is an observational study and there is no control group. Hence, the strength of the evidence is low.

A case series study which is also an observational study can be done instead of a RCT. One of the advantages of case series study is that it is low cost and less time consuming. The researcher will identify patients who had undergone FMT by examining their medical records to determine patients’ outcome after been given the treatment. However, case series studies are weaker than RCT because they cannot infer causation as there is no control group and is used to generate a hypothesis for initial reporting on novel therapeutic studies which can be further tested by higher evidence study.

3.6 Purpose of using a RCT
RCT is the gold standard for clinical research as it is at the top of the hierarchy of evidence which makes the result of this study reliable. It is also the most definitive method of investigation and experimentation to establish the effectiveness of a new treatment. In addition, it minimises selection bias which reduces confounding factor. The study is able to prove causation and have a high internal validity.

3.7 Results of the study
The main results of the study showed that FMT is highly effective in treating recurrent C. difficile infection compared to vancomycin therapy. 81% (13 out of 16 patients) of the patient who has FMT are cured after the first infusion. Two of the three remaining patients are cured after a second infusion. Overall, FMT cured 94% of patients with C. difficile infection. For the study group who only takes antibiotic, 31% of them are cured whereas only 23% of the patient receiving antibiotic and bowel lavage are cured. This shows that duodenal infusion of donor faeces in patients with recurrent C. difficile infection is more effective in treating the condition compared to using antibiotics with or without bowel lavage.

3.8 Presentation of the results
The results of the study was presented in the form of percentage, rate ratio and p-value. Patients who undergo FMT had 3.05 times the rate of curing compared to those who take vancomycin alone (99.99% confidence interval [CI], 1.08 to 290.05) and 4.05 times the rate of curing compared to those who take vancomycin with bowel lavage (99.99% CI, 1.21 to 290.12). The overall cure rates of donor-faeces infusion compared to the other two control groups have a p-value of 0.001 and the null hypothesis indicator is 1 which does not fall in the CI which shows that the results were statistically significant and the null hypothesis is rejected as the p-value is below 0.05.

3.9 Ethical issues
There is no ethical issue in the study as all participants has given written informed consent before the start of the study. As this is an open label study, the patients knew beforehand the treatments that are performed on them and the possible adverse effect of the treatment such as cramping, belching, constipation and worsening diarrhoea. The study was approved by the ethics committee at the Academic Medical Center in Amsterdam and the study is constantly being monitored by the data and safety monitoring board.

Alternative study design such as cohort study cause no ethical issue as long as the participants are willing to participate in the study. Furthermore, it does not involve interventional trial, thereby it minimises the occurrence of ethical issue. In case series studies, there may be a breach in confidentiality as the researcher needs to refer to the patient’s medical record to obtain the data for the study.

4.0 Comparison between the media report and the journal article

4.1 Consistency of the media report with the results of the journal article
The information provided in the media report is consistent with the result of the journal article. Both articles reported on the effective use of healthy donor’s faeces infusion into patient who has C. difficile infection. However, the media did not mention that the treatment was given to a specific group of patients with recurrent C. difficile and there were a high amount of patients and doctors who were reluctant in taking the treatment in the early stage of the disease. As a result of the omission, the public may be misled that FMT is the cure for all stages of C. difficile infection

4.2 Advice on the implications of the results for the patient
Firstly, I would read and analyse the journal article that is cited by the media report before conferring with my patients. I shall brief them on the disease process of C. difficile and inform them on the pros and cons of faecal implantation. I shall impressed on them the high success rate of cure with no major adverse effect noted in the article.

4.3 Effects of the findings on health policy making
Further studies have to be carried out to ascertain the questions that are unresolved in the study such as the optimal protocol for donor-faeces infusion, the efficacy of bowel lavage in treating the condition and outcome of the treatment in other centres around the world. As this modality of treatment is relatively new and unheard of in public and even among medical practitioners, the health policy maker should educate the medical practitioners and the public first before offering the treatment to the public. A clear, standard and precise protocol of treatment should be drafted for all practitioners before the treatment could be offered to the patients.

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