The Bolam test for medical negligence in England is determined by establishing that the doctors treatment was in line with the standard practice of a similar, reasonable practitioner. A documented and agreed informed consent between patient and practitioner that concludes that the benefits of the proposed treatment outweigh the risks is a central piece of this. In order for this consent to be informed consent, the highest standard, the benefits and risks much be adapted to the specific circumstances of that patient. By way of example Owlicity has dealt with a claim where a patient who was known to have autoimmune diseases was provided with straightforward aesthetics treatments. The practitioner made no assessment of the potential increased risk of the aesthetics products in the context of these autoimmune diseases and there was a subsequent flair up. The breach of duty occurred because there had been no assessment of the specific risk of the treatment to that patient with their auto-immune diseases.
The pinnacle of risk assessment for treatments is still large scale randomised controlled trials (RCTs). These generate both the overall risk assessment for the treatment and also the contra-indicators and associated risks. Contra-indicators are conditions where the risk is known to cause harm that outweighs any potential benefits. These enhanced risks and contra-indicators are still based on large groups showing the same result.
Personalised medicine is … personal. This means any trial has a sample size of one by definition. One such example is the use of the ketogenic diet (KD) in cancer treatment. The KD diet in cancer treatment is aimed at achieving a ratio of fasting blood glucose to fasting blood ketone of less than one. This requires highly personalised ratios of macronutrients (card, protein, fat) in the diet. Often a patient requires biomarker monitoring and specialist advice to achieve this result.
For example, the degree of personalisation with the KD, in 2017 led to an umbrella term “ketogenic metabolic therapy” (KMT) that includes long-term dietary, physical activity, and lifestyle modifications (requiring objective, measurable biological outcomes). These outcomes and the various levers which achieve them are highly personalised to the individual depending on the specific disease, metabolic health, fitness, age, and general well-being of the individual, among many other factors.
The possibilities for personalisation of KMT are even more nuanced when it is used as an adjuvant therapy with cancer treatments such as chemotherapy and/or radiotherapy. The relevance of KD in cancer treatment arises from the fact that cancer cells are unable to produce energy through oxidative phosphorylation from glucose in mitochondria, but are instead reliant on glucose fermentation and glutamate metabolism for energy.
The goal is to weaken the cancer by starving it of glucose as a substrate for energy and in this weakened state chemotherapy and/or radiotherapy should have increased efficacy.
The proposed ketogenic therapeutic zone is achieved once glucose levels are less than two-fold ketone levels, and is optimal when glucose levels are equal or lower than ketone levels. This ratio is known as the glucose-ketone index (GKI).
Achieving therapeutic ketosis requires highly personalised ratios of macronutrients (carbohydrates, protein, fat) in the diet. Monitoring biomarkers is essential and may require specialist advice to achieve this result. Typically, a KD is initiated via restriction of carbohydrates to between 20-50g/day with associated increases in fat to replace the lost energy from carbohydrates with exact amounts titrated by a therapist to achieve a personalised diet plan.
Personalisation of dietary protein intake requires specialist expertise due to protein having a trade-off as a ketogenic suppressant while also being muscle sparing. This is all the more crucial in cancer therapy because cachexia (muscle loss) is mediated by the disease and preservation of lean body mass is used as an indication of treatment prognosis by oncology teams.
Thus, on the one hand, lean body mass must be preserved by ensuring adequate protein intake, but as protein stimulates insulin production and insulin reduces ketone body output, too much protein may therefore thwart attempts to reach and maintain optimal GKI levels.
The result is from purely observed results there is some clinical evidence for the KD diet for the treatment of cancer, but this is not systemic or conclusive. In these situations it is useful to look to other areas of research. A fertile area is to understand the biochemical process. Research shows that in 50% of melanomas a mutation in the insulin signalling pathway causes malignant melanoma cells to become addicted to glycolysis (glucose metabolism) and this prevents cell death and increases its proliferation.
Drugs can block this mutation, but research also shows that an effective, and more natural, approach is to decrease glucose intake via the KD diet.
With this mechanism, and some its limitation, understood, combined with some clinical evidence that the KD diet is safe and improves quality of life, a robust case can be made for the use of the KD diet in treating cancer.
A number of different approaches can be taken to reviewing the benefits of a treatment. In “Wheel Rebalancing Pyramid: Better Paradigm Representing Totality of Evidence-Based Medicine”, Colleen Aldous et al. break these down into Structured Analysis; Mechanism of Actions; Non-systemic Reviews and Clinical Studies. Owlicity has been working on developing techniques for assessing treatments within this framework.
Treatments that have sufficient evidence of their potential for benefit can be defended under the Bolam Test and thereby can be insured. Owlicity is actively assessing dietary approaches to treating metabolic disease.