We are moving forward in respect of both prevention and treatment of Covid-19. Action is needed, as in the UK we have had 60,000 deaths attributed to Covid-19. There have been more than 1.6 million cases, but it never clear what a "case" means. Even deaths are not clear, and it is always stated on news broadcasts that "There have been 500 [or whatever number] deaths today in people who have tested positive for Covid-19 during the past 28 days". Road Traffic Accidents perhaps?
In the UK there have been approximately 25x more cases than deaths, whereas internationally it is 50x more cases than deaths. The geography of Covid-19 is another story, but the UK is not doing well. We have now reached in excess of 900 deaths per million, among the highest in the world.
How good have our interventions been? We cannot have confidence in our physical policies of distancing, closure of schools, universities, places of worship, workplaces, restaurants, sports venues, social occasions including weddings and funerals, family contacts etc. There has been a huge social and economic price to pay for little if any gain.
An immunological approach has always held more promise, with massive investment in the production of vaccines. However there has been complete neglect by governments of correcting wide-spread vitamin D deficiency. This is despite the knowledge that vitamin D is essential for unlocking defensive immunity, and ignoring several research observations of the bad outcome and death from Covid-19 in those deficient.
I will look at vaccines next time, but for today I will keep to vitamin D to explain how "efficacy" is worked out.
I have described in previous posts the powerful trial from Córdoba concerning the hospital treatment of patients with Covid-19 pneumonia. The study used the rapidly-acting part-activated form of vitamin D, namely Calcifediol, or 25(OH)D, a natural product. We have seen the pathetic superficial rubbishing by the UK National Institute of Health and Care Excellence (NICE), with instruction not to use Calcifediol. In contrast a detailed analysis at the Massachusetts Institute of Technology (MIT) identified no procedural fault and a less than 1 in a million probability of the positive result being due to chance.
I would like to analyse the results of the Córdoba study to assess the efficacy and economic value of Calcifediol.
There were 76 patients in the study, all admitted to hospital on account of Covid-19 pneumonia. They were randomised into two groups, 2:1 ratio treatment:control. Treatment was started on admission to hospital with standard high quality care with or without Calcifediol. The main outcome end-points were the need for admission to ICU and death.
Calculation of Efficacy
Placebo control group of 26 patients:
13 ICU transfers = 50% ICU transfer rate, 2 deaths
Calcifediol 50 patients:
Expected ICU transfers would be, from control group,
50% of 50 = 25
Observed ICU transfer was 1
Therefore ICU transfers prevented by treatment were
25 (expected) -1 (observed) = 24
24 out of 25 ICU transfers = 96 out of 100
Efficacy = 96%
Absolute or proportionate benefit
The reduction of ICU transfers was 50% to 2%
50% - 2% = 48% absolute benefit from Calcifediol
And for the usual amplifying spin:
48% of 50%
(48 x 100) / 50 = 96% proportionate benefit from Calcifediol
Calculation of NNT
In the Calcifediol treated group of 50
1 ICU transfer = 2% ICU transfer rate
50 patients treated with Calcifediol reduced ICU transfers by
25 expected - 1 observed = 24
50 Calcifediol treatments to prevent 24 ICU transfers
50 ÷ 24 = 2 patients needed to be treated to prevent
1 ICU transfer
number needed to treat to prevent on endpoint of ICU transfer
NNT = 2
Cost–benefit analysis Updated December 15th
The principle is that the cost of all the patients treated must be borne by the ones who benefit. Therefore with an NNT of two, the cost of twor treatments is the cost of preventing 1 ICU transfer
= 2 x cost of one course of Calcifediol
In Spain the price charged for Calcifediol is €10.32 for 10 softgels each containing Calcifediol 266 micrograms.
In the Córdoba RCT and on the package show, the dose is expressed as 0.266mg. Decimal points can be confusing and so the dose is better written as 266 micrograms, using full text for micrograms as abbreviations can also be confusing.
The course of treatment is:
day 1, 532 micrograms,
day 3, 266 micrograms,
day 7, 266 micrograms,
day 14, 266 micrograms,
This is 5 soft gels, a total cost of €5.16, £4.68, $6.27
The cost of one ICU transfer or one death prevented
= NNT x €5.16
= 2 x €10.32
= €11.32, £9.36, $12.53
Treatment with Calcifediol will result in substantial savings of money as well as deaths. One day on an ICU cost approximately £2,000.
What about deaths prevented?
In the control group there were 2 deaths, all in the ICU.
In the Calcifediol group there ware no deaths.
2 versus 0 does not lend itself to statistical calculation.We cannot assume a 100% reduction in deaths.
There was a 96% efficacy in the reduction of ICU transfer and the must have been an efficacy in the reduction of deaths greater than 96%.
Analysis will follow in the next post.