In developed countries, the general consensus is that if you do not die of heart disease, then the next likely event is cancer.
As a condition that is bound to haunt a significant proportion of the population, we have been searching for cures for cancer for hundreds of years.
However, over 200 years later, exactly how effective are our drugs?
Effectiveness of DrugsFrom 1991 to 2019, mortality rates from cancer fell by 32% as cancer survival rates increased.
It should be noted that early prevention, detection, and other methods are also not perfect. They can cause overdiagnosis and overtreatment.
Additionally, some cancers progress slowly, and patients will have a longer survival period, which increases the numbers.
In that case, how effective are cancer drugs?
The study examined the drugs' response rates (RRs), a measurement that quantifies how well the patient’s tumors respond to the drug.
The authors found the median RR was 41%, meaning that, at the median, only 41% of patients’ tumors responded to the drug. Breaking the results down, of these 85 approved drugs, 14 (16%) had an RR less than 20% and almost half (47%) had an RR less than 40%.
This indicates that the 14% of novel drugs approved over 5 years, replaced standard lines of treatment.
However, the majority of the novel treatments were only approved add-on treatments (29%) which complemented the main treatment or as alternatives (42%) to the standard treatment.
Therefore, most novel cancer drugs are complementary, rather than a treatment that overturns the standard regime. The authors stated that while complementary treatments can be beneficial, the addition of another drug to the regime also generates more cost for patients.
Newly-approved drugs are either novel (a new molecules or acting on a new pathways) drugs or a generic version of a previously branded or patented product.
The majority of drugs approved by the FDA are generic drugs.
This is because generic drugs are not tested for safety, only for bio-similarity to the branded drug already on the market: such as the absorbance rates, the concentration of the active compound, and so on.
Generally these drugs are just as safe as the branded version, and are also significantly cheaper.
The Food and Drug Administration (FDA) has also previously banned generic medications manufactured at several Indian sites.
In contrast, novel drugs will generally go through a more stringent approval process; tested for safety and efficacy as part of the approval process.
However, novel drugs are not without risks either.
Many studies have found that though novel drugs are usually more effective, they are also more likely to be toxic.
Transparency, Data Protection, and Intellectual PropertyThe pharmaceutical and regulation sector is entrenched in intransparency and corruption.
Many research and media reports blame the lack of transparency, undisclosed clinical data as a sickness endemic to the oncology drug industry as well as the pharmaceutical sector in general.
In many cases, it is true: only a small number of people have the data and it can even be difficult for insiders to access critical clinical data.
However, the delicate balance between data transparency, compliance to data protection laws, and the need to protect intellectual property has made full disclosure of clinical data trials difficult.
In 2007, the Food and Drug Administration Amendments Act of 2007 (FDAAA) gave the FDA more power to require post-approval studies from drug manufacturers.
The regulatory body could also impose monetary penalties if manufacturers are noncompliant.
The FDAAA also required information on the design of all clinical trials, the summary of the results also had to be made public on ClinicalTrials.gov 12 months after study completion, as well as other changes.
However, much of the patients’ data from clinical trials for cancer drugs is not public, despite this legislation.
Studies evaluating transparency for pharmaceutical clinical trials often return with findings that leave much to be desired.
The authors found that of the top 10 anti-cancer medications in global sales, nivolumab (immunotherapy for melanoma), pembrolizumab (immunotherapy for many cancers including melanoma and breast cancer), and pomalidomide (chemotherapy for multiple myeloma) had less than 10% of their data eligible to be made public.
A major reason for controlled access to patient data and clinical study reports is because these data may contain sensitive data, and there are stringent legislations in place to protect such private data.
In 2018, the European Union (EU) enacted the General Data Protection Regulation (GDPR).
The GDPR is a legal standard that protects personal data of EU citizens.
It affects any organization that stores or processes their personal data, even if it does not have a business presence in the EU, encompassing data for health and medical fields, online industries, and many more.
HIPAA entails U.S. privacy laws on sensitive health information of patients and consumers. It generally is not applied to pharmaceutical firms, but becomes relevant in clinical studies.
Though some data may be suppressed due to unfavorable findings, often data is only made accessible to a very small number of people partaking in the research.
This can often leave people working in the firms and in drug development, in the dark.
Many large firms contract third-party research groups to conduct their trials, and this adds layers of complexity on who is able to control, analyze, and process the data.
Not to mention that the risk of intellectual property theft increases as more people are able to access the records. China, India, Iran, and Russia have long histories of intellectual theft, and in the era of technological advancements, these concerns become increasingly relevant.
Expedited ApprovalsThough it may seem easy to point the finger at Big Pharma, a study published by BMJ shows that drug regulatory bodies have also added fuel to the production pipeline that is delivering drugs at low clinical values.
Over the years, drug regulators have progressively lowered the bar on data quality for trials.
Surrogate markers are the easiest markers to use in clinical trials, they are also the most unreliable.
This is because they measure biological signs that may indicate improvements in disease rather than improvements in patients' symptoms and tumors or reported symptoms by patients.
The FDA has also increasingly given out expedited approvals.
Accelerated approval is supposed to be only granted to drugs that indicate a clinical benefit that gives significant advantage over available therapies. Though it is intended to give patients the best available treatment, the reality is the reverse of such intentions.
Since expedited approval is mostly based on surrogate endpoints, it has a lower data integrity. These drugs are therefore at a higher risk of having lower clinical values.
For the many oncology drugs that were fast tracked and approved, many post-market studies show that these drugs have no significant clinical benefit or advantage over available therapies and become a misallocation of money and resources instead.
Since the FDA introduced the expedited approval pathway in 1992, only 16 drugs have ever been withdrawn.
In some cases, confirmatory trials were never done.
Meanwhile, the FDA has also become increasingly less rigorous with their market withdrawal decisions.
“If the FDA feels an applicant’s processes, adherence to processes, or reputation is not pristine, the FDA will require additional support to prove lack of ‘guilt’. Many recalls are now based on ‘lack of assurance’ of GMP (good manufacturing practices), as opposed to the finding or likelihood of defects,” the authors of the report wrote.
Such is the FDA's blundering acts of a market takedown of JUUL in June 2022 over lack of evidence of product safety, only to lift the ban a month later after pressure from the public and legislators.
Pharmaceutical PatentsPatents, the exclusivity to manufacture and use a pharmaceutical agent, provide high profits for pharmaceutical firms.
90% of drugs fail in clinical studies, so patents maintain the competitiveness of pharmaceutical firms by preventing the theft of intellectual property and give revenue flow to finance research and development (R&D).
Since chemical products like pharmaceutical agents can be easily reverse engineered by basing it on the drug’s trials and research studies, trade secret laws cannot provide very meaningful protection.
Patents also come with negative consequences: including high market prices and overpromotion of patented drugs, as well as extension of successful patented products through evergreening (patenting “new inventions” that are really just slight modifications of old drugs).
Further, there are also costs that companies need to consider to register and maintain a patent. At minimum, companies will need to pay for administering a patent system for their agent, for litigation costs associated with determining the validity of a contested patent, for rent-seeking conduits to maintain or extend patents, for account costs that were misallocated during research and development, for engaging in cartel-facilitating conduct (such as striking a deal with other generic pharmaceutical companies to not make a generic version of the drug until a certain date), and so on.
Legislative efforts to control drug prices have often been met with industry objections that those efforts would lead to less cutting-edge technology. Though there is no question that some of the patent-generated revenues are reinvested in R&D for new drugs, companies also spend very substantial amounts—often even more than R&D—on advertising and promoting patented drugs.
The FDA gives a patent term of 20 years from the day the company applies for a patent on the molecule and before they start R&D. Therefore, once the drug makes it into the market, the patent period is significantly less than 20 years.