Late Phase Studies: The Possible Revolutionary Trails
The current late phase market in India is close to 60 million US Dollars which accounts for about 15 % of the total clinical research market. At present phase IV and Post Marketing Surveillance (PMS) studies mainly contribute to the late phase market in India. PMS market is likely to grow faster as DCGI is insisting to do PMS studies on new drugs, new biologics and follow-on biologics/biosimilars before or after launching in India. As health insurance is gaining wide acceptance, cost effectiveness and quality of life assessment studies like outcomes research is the new area which would gain momentum in few years.
Phase I studies are conducted to assess the safety and tolerability of a drug which can take several months and involves a small number of healthy volunteers (20 to 100). Phase II studies test the efficacy and further safety of a drug which can last from several months to two years and involves up to several hundred patients. Phase III Clinical trials conducted after efficacy of the drug is demonstrated, but prior to regulatory submission of an NDA which can last from several months to several years and involves several hundred to several thousand patients. Phase III B Clinical trials are conducted after regulatory submission of an NDA, but prior to the drug approval and launch. Phase III B and Post marketing trials are considered as late phase clinical studies which are conducted to establish long-term safety and efficacy of a drug in real-world conditions over an extended period of time.
Most of the clinical trials and post marketing drug safety data is collected from subjects who have been exposed to the drug for few years. But some health risks may not be identified unless a person has been exposed to a substance for 5, 10, 15 or more years. For example a chain smoker will not develop lung cancer until they have smoked for at least 25 years. So late phase studies are conducted to monitor a drug's long-term effectiveness and impact on a patient's quality of life over an extended period of time.
Early phase studies specifically address drug safety and efficacy but they do not detect unforeseen risks of a drug. Example: Nimesulide is a good example. It is an orally administered non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic and antipyretic effect .Nimesulide was first launched in Italy in 1985, since then it has been aggressively marketed in about 50 countries throughout the world. Safety data from clinical trials proven Nimesulide as a preferential COX-2 inhibitor and therefore, assumed to be safer in clinical use but selective inhibition of COX-2 effect on the GI tract was detected only after various epidemiological studies.
Late phase studies provide valuable ongoing safety information for risk management through long-term tracking of patients in a real-world clinical setting. Additionally, these studies can target particular therapeutic areas or specific populations where relevant clinical data are required to ascertain the effectiveness and utilization patterns of some product.
The information gained from such studies helps in bringing out the long-term risks of drugs which can play an important role in health promotion and disease prevention. The global regulatory bodies could use this data from long-term drug studies to make required changes in labeling and medication. guidance.
Late-phase studies correlate the drug with real life scenarios. For example - In a real-world setting, patients may take several therapies (Polyphramacy) for different diseases. So In addition to controlled pre-marketing clinical trials, it is important to monitor the safety profile of a new drug once it is widely available. This Study will also solve the food drug interactions and drug-drug interactions due to Polypharmacy.
Late phase illustrates the difference between efficacy and effectiveness. Example: Minoxidil was first used exclusively as an oral drug to treat high blood pressure. However long term studies shown its side effects as increasing growth or darkening of fine body hairs. From this result a topical solution that contained 2% minoxidil was produced to treat baldness and hair loss.
Efficacy is judged within the controlled environment of a clinical trial with strict inclusion and exclusion criteria and close monitoring and ensured compliance. Effectiveness is the real test of a drug when it is used in a much larger population, with varied organ system function, concomitant drugs and where monitoring and compliance are not always ensured. It is a non interventional study requested by regulatory authorities to vary the safety, tolerability, and effectiveness of a marketed drug in a particular population as per the locally approved label. In India, If DCGI suggests, PMS data should be submitted to the DCGI within 2 years of product launch.
Types of Late Phase Studies:
Late Phase Studies are an integral component of the commercialization effort for a product because it impacts multiple aspects of ongoing clinical and commercial support. Hence Late-phase studies provide more comprehensive data about overall treatment satisfaction and patient HRQoL (health related quality of life) in real-world settings over an extended period of time to detect any undiscovered effects, positive and negative, that may be associated with a drug which may not be possible in earlier clinical trials.Pharmaceutical companies need to get to grips with late-phase clinical studies if they are to differentiate their products and build a comprehensive value proposition in an increasingly saturated and payer-dominated marketplace.