Seven patients discontinued or were otherwise lost to follow-up. Ten (11%) of 85 patients on combination treatment reached the combined primary endpoint compared with 20 (23%) of 85 on trandolapril alone (hazard ratio 0·38, 95% CI 0·18—0·63, p=0·018) and 20 (23%) of 86 on losartan alone (0·40, 0·17—0·69, p=0·016). Covariates affecting renal survival were combination treatment (hazard ratio 0·38, 95% CI 0·18—0·63, p=0·011), age (1·30, 1·03—2·29, p=0·009), baseline renal function (1·80, 1·02—2·99, p=0·021), change in daily urinary protein excretion rate (0·58, 0·24—0·88, p=0·022), use of diuretics (0·80, 0·30—0·94, p=0·043), and antiproteinuric response to trandolapril (0·81, 0·21—0·91, p=0·039). Frequency of side-effects with combination treatment was the same as with trandolapril alone.
Combination treatment safely retards progression of non-diabetic renal disease compared with monotherapy. However, since some patients reached the combined primary endpoint on combined treatment, further strategies for complete management of progressive nondiabetic renal disease need to be researched.
These are very disturbing reports of fraudulent publications in Japan relating to the efficacy and superiority of RAAS inhibitors whether Trandolapril in combination with Losartan on the progression of CKD (Nakao et al) or the Kyoto Heart Stduy on Valsartan cardioprotective effects independlently of changes in BP...so why is this taking place in Japan but undoubtedly elsewhere.
Back to Bad Pharma...and Bad Doctors....but alo Japan...
Most clinical traisl of new therapeutic agenst are sponsored by the Pharmaceutical Industry; Good Pharma, without it we wouldnt be treating many life threatening medical conditions.
1. Most clinical investigators in many emerging (and emerged as well...) countries are targeted by the Pharma industry; they are receiving remunarations for their involvement in such clinical trials; in the form of money, in the form of recognition, in the form of prominence and fame in their profession...doctors like all humans are responsive to such incentives...
Consequently, doctors and invetigators involved in clinical trials want to please their paymater...the Big Pharma who recruits them.
2. Pharma analyses the result of the RCTs they sponsor....statisticians and analysts employed by the Pharma company almost exclusively analyse the result and data of the study; they "clean" it..."process"...it and ultimately provide investigators with a sanitised version of the outcome of the trial...
This is dangerous as it invites manipulation of the data by the Pharma employees to please their paymaters....Bad Pharam!
This has come to light in the UK with a major Pharma company in a trial on osteoporosis where the raw data emanating of the trial were not shown or shared with the investigators but instead the sanitised version of the Pharma analysis leading to questions posed by the likes of Dr Aubrey Blumsohn (who wasnt paid by them) about the conduct of senior investigatores including Prof Richard Eastell (who was a senior consultant to the Pharma):
3. Next, why are these fradulent reports emanating repeatedly from Japan?
This brings to mind issues relating to Japanese culture, and the deferential approach to authority and seniority.
Dont challenge, dont question...authority; If the Professor says that the trial is positive....who is the junior investigator or company employee to challenge him (seldom her...). Whistleblowing is not yet part of japanese culture. Whistelblowers are fired...marginalised or even prosecuted...this was highlighted in the report by Michael Woodford, who was the Olypmus camera company Chief Executive Office (CEO), who reported alarmingly bad and fraudulent practices in the Japanese company he was head of; he was fired and sued by the company! he wrote "EXPOSURE" counterattacked and got vindicated as bad and fraudulent practices were confirmed and the company found guilty of malpractices...
He wrote a book: "EXPOSURE" that puts the fraudulent practice of Olympus in the context of the Japanese society and its culture. he attributed malpractices in Japan industry to over-deferential attitude to authority and seniority. This may also be symptomatic of japanese healthcare companies and medical investigations.
WHISTELBLOWING IS HEALTHY AND OFTEN JUSTIFIABLE....BUT THE WHILSTLEBLOWER SHOULD BE WILLING TO PUT HIS JOB ON THE LINE AS DR AUBREY BLUMSOHN AND MR MICHAEL WOODFORD DID...they both rendered a huge service to probity and transparency in Pharma and Industry in general!
BIG PHARMA needs to think again the conduct of their clinical trials....BAD DOCTORS need to be checked and challenged by those working with them and collaborating in their clinical investigations worldwide...as Scientifc Fraud is not a Japanese Exclusive....it is prevalent worldwide:
This is very nciely reviewed in this BMJ paper, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702092/?report=classic,
Lack of Ethics
Academic and Professional Rewards
But also Lack of Institutional monitoring and vigilance
A Must read for all clinical investigators!