On 2014 Apr 19, Karthik Balachandran commented:

The authors describe an industry sponsored and industry designed trial of saroglitazar- a dual PPAR alpha and gamma agonist, explaining establishment of safety and efficacy as the raison de etre. However, closer scrutiny raises several questions.

1.First of all, the value of triglyceride reduction has not been clearly demonstrated in patients with type 2 diabetes. In fact, the largest trial on lipid management in diabetes till date- the ACCORD LIPID trial shows that the additional triglyceride reduction with fenofibrate was not useful for CV mortality reduction. Thus targeting “residual cardiovascular risk” in statin treated patients is questionable, especially with the surrogate endpoints- lab values- instead of real world outcomes like mortality or cardiovascular events.

2.More importantly this trial includes patients whose triglycerides were not adequately controlled on statin therapy. The dose of atorvastatin used(10 mg) given for a period of 4 weeks, is hardly the maximum dose or the duration that can be called as “inadequately controlled on statin." 3.Furthermore, the authors compare saroglitazar with placebo for no sound scientific reason. The use of inappropriate comparator has the potential to make the study drug look superior because it has been compared with a dummy sugar pill!

4.The drug is declared safe with 12 weeks of data and a voluntary(read optional) 24 week visit. This is especially important as the predecessors of the drug(muraglitazar and aleglitazar) were discontinued due to increased all cause and cardiovascular mortality. It is unlikely that the cardiovascular safety of any drug can be ascertained in the short time of 12 weeks. One must bear in mind that drugs for dyslipidemia are taken life long.

5.The study was conducted in 29 centers across India to get a sample size of 302. As the cost of training personnel is less, the integrity of data is more and is eminently possible to get 300 odd diabetics from any single center of a populous country like India, it makes one suspect whether this was a seeding trial. A seeding trial is done with the express purpose of giving marketing advantage to the company and not to glean any useful scientific information. Use of prominent senior academics as the authors means their name exists for the purpose of giving the illusion of scientific rigor. This combined with manuscript preparation and editorial assistance by the company employees manufacturing the drug means, this could be a ghost written document- promotional material masquerading as an academic article.Although seeding trials or ghost writing  is not illegal, it is considered unethical.

6.The article also mentions that the trial was approved by ethics committee of individual sites, many of which are private clinics.It is difficult to believe that private clinics have independent ethics committees. So, the question remains - does the drug do anything that cannot be done at half the cost by existing medicines? Is it safe in the long run?

On 2014 Apr 19, Karthik Balachandran commented:

The authors describe an industry sponsored and industry designed trial of saroglitazar- a dual PPAR alpha and gamma agonist, explaining establishment of safety and efficacy as the raison de etre. However, closer scrutiny raises several questions.

1.First of all, the value of triglyceride reduction has not been clearly demonstrated in patients with type 2 diabetes. In fact, the largest trial on lipid management in diabetes till date- the ACCORD LIPID trial shows that the additional triglyceride reduction with fenofibrate was not useful for CV mortality reduction. Thus targeting “residual cardiovascular risk” in statin treated patients is questionable, especially with the surrogate endpoints- lab values- instead of real world outcomes like mortality or cardiovascular events.

2.More importantly this trial includes patients whose triglycerides were not adequately controlled on statin therapy. The dose of atorvastatin used(10 mg) given for a period of 4 weeks, is hardly the maximum dose or the duration that can be called as “inadequately controlled on statin." 3.Furthermore, the authors compare saroglitazar with placebo for no sound scientific reason. The use of inappropriate comparator has the potential to make the study drug look superior because it has been compared with a dummy sugar pill!

4.The drug is declared safe with 12 weeks of data and a voluntary(read optional) 24 week visit. This is especially important as the predecessors of the drug(muraglitazar and aleglitazar) were discontinued due to increased all cause and cardiovascular mortality. It is unlikely that the cardiovascular safety of any drug can be ascertained in the short time of 12 weeks. One must bear in mind that drugs for dyslipidemia are taken life long.

5.The study was conducted in 29 centers across India to get a sample size of 302. As the cost of training personnel is less, the integrity of data is more and is eminently possible to get 300 odd diabetics from any single center of a populous country like India, it makes one suspect whether this was a seeding trial. A seeding trial is done with the express purpose of giving marketing advantage to the company and not to glean any useful scientific information. Use of prominent senior academics as the authors means their name exists for the purpose of giving the illusion of scientific rigor. This combined with manuscript preparation and editorial assistance by the company employees manufacturing the drug means, this could be a ghost written document- promotional material masquerading as an academic article.Although seeding trials or ghost writing  is not illegal, it is considered unethical.

6.The article also mentions that the trial was approved by ethics committee of individual sites, many of which are private clinics.It is difficult to believe that private clinics have independent ethics committees. So, the question remains - does the drug do anything that cannot be done at half the cost by existing medicines? Is it safe in the long run?