Trials and Errors
A trial and error, the dictionary defines as a method of reaching a correct solution or satisfactory result by trying out various means or theories until error is sufficiently reduced or eliminated. There is, therefore, nothing wrong in a trial and error per se provided there is a method and logic to it. When you consider the clinical trials scenario around the world in general and particularly in India, there seem to be more errors than trials.
In a trial and error method of learning, you ask questions, create experiments to answer those questions, and modify your experiments when things go wrong. While you may obtain the best possible solution through this trial and error method, it could take a very long time. The cost of trials and errors is just too high and that makes it (the process) inefficient.
Computer simulation of clinical trials has evolved over the past three decades from a simple instructive game to full simulation models yielding pharmacologically sound, realistic trial outcomes. In addition significant advances are being made continuously over the years in our understanding of biology, physiology, and pharmacology. When you take all these into account the errors in clinical trials should be minimized as compared to the period when the understanding and accumulated body of knowledge in these fields was relatively lower than now. Increased knowledge and understanding should logically result in lower error-rates.
Why is it that there is a huge overcast of doubt on the industry-funded trials? In a study conducted by three researchers from Harvard and Toronto, they observed that 85 per cent of the industry-funded studies were positive as compared to the 50 per cent of the government funded trials.
Glen T. Clark, DDS, MS, and Roseann Mulligan, MS, in their January 2011 Journal of Prosthodontic Research article on Common mistakes encountered in clinical research. Here are the common mistakes novice researchers often make while planning, conducting, and writing a clinical research project. Most of these errors are avoidable.
- Failure to carefully examine the literature for similar, prior research
- Failure to critically assess the prior literature
- Failure to specify the inclusion and exclusion criteria for your subjects
- Failure to determine and report the error of your measurement methods
- Failure to specify the exact statistical assumptions made in the analysis
- Failure to perform sample size analysis before the study begins
- Failure to implement adequate bias control measures
- Failure to write and stick to a detailed time line
- Failure to vigorously recruit and retain subjects
- Failure to have a detailed, written and vetted protocol
- Failure to examine for normality of the data
- Failure to report missing data, dropped subjects and use of an intention to treat analysis
Matter of Concern
While trials and errors are a part parcel of the experimentation process, frauds are not acceptable. An error most often is unintentional whereas a fraud is intentional and deliberate for personal gain. Fraud is a dishonest calculation for advantage. It cannot be tolerated.
It is the increase in fraudulent behavior of Pharma that is a matter of great concern. It spans the entire gamut of product development and marketing. It happens in clinical research and marketing, the two most important areas of pharmaceutical business.
Fraud in Clinical Research
Fraud in medical research has a long and well-documented history. Classic episodes of fraud in contemporary research range from Gregor Mendel’s data on characteristics of garden peas to the whistle blowing of Dr. John Darsee’s, where he was caught faking data in a heart study at Harvard.
There seem to be at least three motives for committing fraud in clinical trials. The number one motive is monetary gain, and enhancement of prestige. Paying the investigators per subject recruited for the trial is a common practice. Therefore, the more subjects recruited, the higher the monetary gains and the investigator’s prestige among peers. The second motive is fabrication of the data essentially to cover up and compensate for laziness, and sloppiness in data collection. Including subjects who would otherwise be excluded is the third motive. Sometimes an investigator may feel that it is in the patient’s best interest to get medical care to be included in the trial irrespective of the exclusion criteria.
The most common fraudulent practices in clinical trials are fabricating missing measurements, falsifying eligibility and not reporting adverse events. Hiding and concealing negative data and publishing only the positive data seems to be on the increase. As recently as in April 2013, a British scientist convicted of scientific fraud for falsifying research data and has been sentenced to three months jail under the UK’s Good Laboratory Practice Regulations.
The fraudulent behavior in marketing areas include bribing the doctors, hospitals, regulatory authorities, and government agencies to get prescriptions and sales for their brands and for enhancing prices. Illegal promotion, which is promoting the products for UN-approved conditions is another example of fraudulent behavior.
Recent news out of China raises the doubt again whether one can trust any aspect of pharmaceutical business. Chinese authorities announced that they were investigating Glaxo SmithKline and other Pharma majors for bribing doctors, hospitals and government officials to buy and prescribe their drugs. Glaxo is accused of using a Shanghai travel agency to funnel at least $489 million in bribes.
Gao Feng, a Public Security Ministry official in China said at a July 15 briefing, “I need to remind foreign pharmaceutical companies that, because they occupy a leading position in the industry and reap huge amounts of commercial profits, they should also bear a great responsibility to society and the public. While we don’t expect them to set a moral example, we expect them to obey the law.”
Erica Kelton rightly asks in her Forbes article of July 29, Is Big Pharma Addicted to Fraud? How else can you explain the attitude of Pharma, which has paid more than $30.2 billion in civil and criminal penalties to the US and state governments in the recent past and continues to face more allegations of wrong doing?
Has fraud become too profitable a habit to kick that Pharma is unable to cure its own disease? If Pharma cannot find a cure for its fraudulent behavior it’s time for the regulators worldwide to find a remedy and stop this. It should be on top of their priority list.