We have come a long way since the discovery of electronic aspects of coronary activity in the mid 1800's.
We have learned a lot since the first ECG machines made their appearance and revolutionized basic concepts of monitoring and diagnostics.
However, from the initial phases of drug development to drug introduction in the general public, there is a missing link in the chain when it comes to safety.
What can ECG results teach us during the clinical trials phase for a safer outcome and more successful treatments? One aspect of clinical trials, and research and development (R&D) for that matter, that must be taken into consideration is the variables, the unknowns.
During the developmental and testing phases, control groups are typically well accounted for, thoroughly evaluated, and vigorously monitored.
After successful testing in the trial phase for the control groups, often times the preliminary field tests will show the adverse effects that a particular drug may have on patients.
While this information is very useful and certainly deserves attention it is not the end-all of what the healthcare industry or the FDA itself may otherwise believe is a perfectly safe drug.
Those aspects out of R&D's control are immediately a liability to the manufacturers the moment the drug hits the public market.
The unfortunate thing about humans is the fact that we make mistakes.
A physician prescribes a new medication that has successfully passed the trial phase with the good faith that their patient will take as instructed.
Patients make mistakes, ignore strict orders, lie about medical history, or simply misread warning signs.
Generally the majority of adverse effects of drugs are due to inappropriate formulations, or excessive exposure to the agents.
This does not even factor in the idiosyncratic reactions whereby a drug is taken as directed however the individual patient has unexpected differences in absorption, distribution, metabolism, or genetic predispositions.
Post-market surveillance is rigorous for new drugs as often times these unknown variables result in the undesired effects.
Globalization is an intriguing idea for tackling the idea of the unknowns.
Globalization and ECG have been working together to asses the results of cardio drugs in the early stages.
A global effort can certainly diversify the target population thereby theoretically honing in and better understanding the adverse effects that can be expected through demographics or individuals who are more likely to show signs of these effects.
Globalization has certainly not been the life saver that the industry had hoped for, but having a diverse target can certainly help solve some of the questions pending.
The key to innovation with global efforts, is doing things in a different way as David Lester explains, "The biggest concern with globalization is that if a research center opened in China, would they do research the same way they did it in Connecticut? If it's not working in Connecticut, why would it work better in China?" This provides some food for though for those R&D companies who may be considering an alternative to U.
S.
based populations and research.
Disruption of regular and rhythmic QT waves is the leading cause of drugs being removed from the market.
ECG readings provide early warning signs to undesired effects of test drugs and therefore must be preformed regularly to prevent wasted resources in later stages of development.
Learning about irregular QT readings at the approval stage is simply inadequate.
Regulartory guidelines have stipulated the importance of drug-induced delayed repolarization (prolonged QTc interval) in cardiac safety assessment.
It has been found that QT/QTc can report repolarization quickly and accurately.
This presents some pretty hard truths to drugs seeking market approval who must are forced by regulation to return to the Phase I testing stages of development.
Regulations such as this though imposing, in the long run offer many benefits including improved accuracy for drug targets, better responsiveness on the part of the patient, consistency among test subjects, and assurance of compliance.
Furthermore, drug ECG testing lends itself to qualified results thereby eliminating adverse effects and honing in on desired results.
David Lester reminds us to be wary of production pushes, "The question is, why do they have to make 40 new compounds? The answer is because they have a quota for revenue.
I suggest that they should make five good compounds.
That is just not the way they do things anymore, because the blockbuster days are over.
" Another way to combat unsuccessful drugs, which is still a problem with ECG testing, is the sample size of test subjects.
Often times drug developers are left to their own devices and must surmise what they can from the group they assume.
One reason for the lack of adequate sample subjects is the general public's opinion of the pharmaceutical industry.
It should not come as a shock that public opinion in the U.
S.
of the pharmaceutical industry is extremely low.
The pharmaceutical industry has the unique juxtaposition of being industry-push as opposed to market-pull.
Consumers of the products that the R&D manufacturers develop are prescribed their product; they do not choose the product from a variety of alternatives.
If the industry could improve its image, improve results would be the ultimate result.
Patients would be more willing to participate in clinical trials, they would be more knowledgeable about industry efforts, and manufacturers would see better accuracy and thus profits.
Again, public opinion is not the cure all of the pharmaceutical industry either, but it is an important characteristic.
The public certainly does not drive this industry, but it plays a key role in the industries success, both in terms of patient outcomes and overall profitability.
Measuring cardiac toxicity is an essential feature driving the increased interest in ECG testing.
However, regulatory compliance is what is making ECG testing essential.
The "Regulatory ECG Imperative for Cardiac Safety" has been the catalyst which has pushed ECG to the forefront of safety.
2 One key component of ECG and QT monitoring yet to be discussed is innovation.
As this has been a commodity rather than a requirement until recently, R&D and clinical trials organizations alike have had the luxury of trial and error on their side.
The difference now is that they are regulated and as such they are charged to come up with innovative techniques for drug development and subsequently, clinical trials.
Has innovation come from globalization? Perhaps to some extent.
Has innovation come from high throughput screening (HTS)? Maybe a little.
Will ECG turn this trend around? It is the question that is on the minds of developers, shareholders and investors alike.
One way that it is being answer is through application of ECG testing.
Two variations provide powerful insight into short-term and long-term effects.
It will be interesting to see if ECG testing proves to be an enabler or inhibitor of drug discovery, manufacturing, and clinical trials.
There are many unknowns with ECG diagnostics.
For every wrong answer there is a new possibility that presents itself.
For example, Drug X led to inconsistent heart rhythms, answer "why" and developers may be one step closer to a breakthrough.
New ideas and concepts are needed to answer these questions and therefore are forcibly approached; regulation is making sure of this fact as the FDA is a proponent of ECGs.