Price of innovation; Why new drugs break the bank?
“Medicine is a science of uncertainty and an art of probability.”
– William Osler
Over the decades with the complexity of diseases becoming more perceptible, the amount of research, development and costs, pharmaceutical industry has to put in developing new drugs and therapy have spiked. The new molecules developed have to undergo a set of trail and error to pave it’s way into the market.
The below multiplex methodology makes it tedious and expensive;
- Length and costs; Drug development and research is expensive and long. It takes around 12-15 years and cost between $314 million – $4.46 billion.
- Phases of drug development:
Discovery and pre clinical phase: After the ideation of a compound, it is screened by various techniques for efficacy, toxicity, pharmacokinetic and safety information. Wide doses of the drug are tested using in labs in test tube or cell culture, that is known as in vitro experiments, next phase involves trying out in animals or the in vivo experiments, and it is also possible to perform in silico profiling using computer models of the drug–target interactions. The investigator then reports this data to the FDA as Investigational new drug application (IND), then the sponsor must wait 30 calendar days before initiating any clinical trials. Costs here, range from $15 million to $100 million.
Clinical trial phases:
- Phase 0: Involves 10-20 people. A small dose of drug is given to the patient to identify if the drug behaves as per the data from lab studies. The cost of the program is $0.7–1.25 M.
- Phase 1: Involves 20-50 people. This phase aims to evaluate the best dose, side effects and what the drug does to the body. The cost for this phase is estimated approximately $25 million. Length of the study lasts for several months and only 70% of drugs move to the next phase.
- Phase 2: This phase takes months to years. Study participants involve around 100 with the disease condition. The study aims to find the efficacy, dose and how well the treatment works. Additional safety data is collected, researchers use these data to refine research questions, develop research methods, and design new Phase 3 research protocol. Only 33% of drugs move to the next phase. The cost averages around $60 million.
- Phase 3: This phase tries to answer the hypothesis, the new medicine is better than the current treatment. The trail involves more than hundreds of participants who have the disease or condition and the lasts for 1-4 years. It’s the most expensive phase averaging at $350 million up to $1 billion for certain drugs. 25- 30% drugs move to the next phase.
Once phase 3 is completed the pharmaceutical company submits the New drug application (NDA) to FDA. The NDA carries all data of the clinical trail phases. On the basis of reports the FDA may grant approval for the therapy with respect to disease or if the evidence outweighs risk then the FDA may ask for further studies to ensure its safety and efficacy.
If the drug is approved, then it may become a standard of care for the disease. Further developments with reference to generic drug doesn’t have to undergo the non-clinical and clinical phases except bioavailability and bioequivalence. Then the sponsor needs to submit an Abbreviated New Drug application (ANDA). Unlike the NDA process this takes less time (1-2 years) and expenditure ($ 2=3 million). - Phase 4: Once the drug receives approval it enters this phase also called as post marketing surveillance . It involves pharmacovigilance . Due to the large exposure of the drug to the patients now, sometimes off label indications, or unidentified adverse events may get reported. It’s the responsibility of the pharmaceutical manufacturer to report it to the FDA and update the patient information leaflets respectively. The drug marketing and promotion costs $8.1 billion as in 2022.
- Patents: Pharmaceutical companies are provided a patent period of 20 years from the time of manufacturing. This allows the manufacturer to increase the price without competition from biosimilars Or generics. Further modifications of molecule or drug delivery system enhances the prices even after the patent expires.
- Economical and financial interests: Though the innovation of drug development and research is meant to meet health needs , ensure therapeutic efficiency, safety and better healthcare. The revenues, shareholders interest and market price doesn’t align with affordability, accessibility and availability.
- Precision medicine and limited competition: Therapies developed and available for rare or genetic diseases faces scarcity. The complex history of the disease and orphan drug designation are often exploited while the drug is exposed in the market.
Strategies for equitable access; Making life saving drugs affordable
Measures for Patient Accessibility Post-Phase 3;
- Pharmaceutical companies should try establishing polices to allow patients who participated in phase 3 access to have steady state supply of free drug or at subsidized cost. This would be beneficial especially for those suffering from genetic disorders where treatment lasts a lifetime.
- Adverse events coverage: The pharmaceutical company should lay out rules to cover any ADRs for those who signed up for trails which further strengths the trust of the patients.
- Early access to new indications; The pharmaceutical company should set polices to help the previously treated groups access to further advancements if any new indication studies are proven.
Patient advocacy groups, integration into healthcare programs and financial support programs are some other measures that can be taken to improve accessibility and healthcare.
The phases of drug development thus is an intricate process where each labyrinths undermines and strengthens the safety and efficacy of the molecule. These phases are essential to deliver quality healthcare to the public ensuring faith in healthcare innovations over year’s. The FDA ensures that these guidelines are followed over all regions of the world. The healthcare professionals and stakeholders should understand these phases, appreciate the complexities involved and should work to make these advancements available to the public, hence improving the health outcome. As rightly quoted; “Medicine is not only a science, it is also an art. It doesn’t consist of only compounding plasters and pills, it deals with the very process of life, which must be understood before they may be guided”.