Cancer is a disease that starts at the molecular level, creates uncontrolled cell growth, and ultimately spreads over the entire body where it can kill the host. Logically, diagnosis and treatment go back to this molecular level in the hope to find a cure or at least to extend meaningful life. The molecular perturbations can be found in cancer tissue itself through a never seen before and rapidly developing technological excellence. Billions of DNA mutations can be found in one working day and per machine. And there is ambition to go down the process of epigenomics, RNA control, and protein characterization and quantification. All with the intend to fully characterize the aberrant metabolic pathways of the individual cancer.
The demand for pretreatment tissue specimen has never been so critical. There is evidence that the need for samples will steadily grow as the impact of molecular biology in oncology increases. Treatment decisions based on personalized predictive and prognostic tests largely depend on this elaborate assessment of biological behavior. The data is almost exclusively obtained from the individual cancer tissue and is, for example, also requested for scientific insights, compliance with international guidelines, up to reimbursement compliance.
New treatments, either immune or targeted, in general, cost well above the Qaly, the budget that can be spent for one extended year of quality life. Almost all Western countries have contemplated about the Qaly and would spend 50000 Euro for a supplemental quality year. But don’t new treatments easily cost 50000 up to 500000 Euro nowadays? The response rates seldom are beyond 20% with an added disease-free survival of barely 3 to 6 months. Not one country can afford them for all their affected citizens. For the health care system to remain affordable, patients and treatments need to be selected through tests that indicate the right anticancer products. But also, predictive and prognostic tests, most of them multilevel (DNA, RNA, proteins…), are complicated. The slightest impurity of the sample can jeopardize the outcome. And because of the intricacy of these tests and related regulatory implications, they are also expensive. Depending on the source and type of service, they cost between 1000 and 15000 Euro. Altogether, the demand for high-quality tissue has never been so precious and debatable at the same time. Patients need results for good cost-effective management, and these are strongly dependent on the quantity and quality of the tissue sample.
Not unexpected, the global biopsy devices market increases annually by 6.8% up to USD 2.42 Billion by 2022. The growth is primarily attributed to the rising prevalence of cancer, increasing demand for minimally invasive surgeries, initiatives undertaken by government & global health organizations to spread awareness about cancer, and the improved reimbursement scenario in most countries.
Reflecting about the drivers for biopsy tissue in oncology, one might think that research institutions and universities combine forces to study the procurement of tissue samples and for industry to jump on this increasing market. One could expect intensive preanalytical research about tissue preservation, storage, and how to make tissue acquisition a comfortable part of the diagnostic work-up?
On the contrary.
What we observe is that research on the biopsy procedure is poor and almost inexistent. Apart from the direct and frontal needles, such as the Spirotome, there has been no real innovation in this field for many years. More, retail in biopsy systems has been cut by large international vendors, such as Johnson & Johnson, Bard and Cook Medical. The former portfolio in these companies has not been replaced by newer products. One must admit: the biopsy market did not see major novelties during the last 30 years and still counts on simple well-known instruments that were created 3 decennia ago. And why not sell a robot-product of 2 M USD instead of many common trucuts that cost 20 USD? The margins are very different indeed.
Why is the need and market increasing, while major vendors decrease and innovations slow down? Why continuing with established medical devices that are good for cytology and histology, but not for comprehensive molecular biology and for information that is needed for modern oncology and tissue engineering?
The answers appear complex and multifaceted.
There is growing attention from the pathologist and molecular laboratory for the quality of submitted tissue and they do not hesitate to report this at the multidisciplinary oncology meetings. The biopsy is becoming a multidisciplinary procedure where endoscopists team with interventional radiologists. The equipment involved is complex, combining endoscopy with ultrasound, (PET-)CT, and MRI scans, and gradually enters the domain of robots. But combination of medical imaging and biopsy devices is not always in favor of better tissue acquisition. Medical imaging companies aim towards the best visualization of the lesion and integrates only marginally the biopsy step. Less attention is going to sophistication of the biopsy instrument part compared to image processing and digital integration with other visualization methods. The shift from the simple biopsy step towards the integration in robot equipment makes the vendors in the field different and not always visible on the traditional biopsy market.
Research on medical devices is becoming almost as complex as for pharmaceutical products. Recent new regulations, such as the Medical Device Regulation (MDR) and newer versions of the ISO 13485, make clinical trials more streamlined and at the same time complex and expensive. During the last 20 years, this research comes practically exclusively from small start-ups that usually suffer from lack of budget and expert multidisciplinarity to bring the medical device at the stage of approval. They disappeared gradually from the scene, leaving an empty space of no research at the commercial end.
The approval of devices is complex with a depressing burden of regulatory requirements and laws. Regulatory authorization is cumbersome and expensive. The typical biopsy instrument is now Class IIb because it is offered to the medical community in sterilized single use version and even Class 3 for the brain and heart devices. The development of the technical file(s) has seen a huge leap in complexity and data handling. The costs of this technical documentation, calculated per type of device, sometimes exceeds the profits from the traditional small margin in manufacturing and distribution. Reducing the number of versions and even stop of the complete gamma is sometimes the only way to keep business running. Regulatory requirements go back in time which explains why some recognized commercialized versions of biopsy instruments disappear from the market.
Even worse is the regulation for new biopsy devices that are considered dangerous and uncomfortable. Hereby discouraging inventors and manufacturers to go for a medical device that creates the highest risk for complications and side effects. For interventional devices scrutiny is more aggressive compared to, for example, a sterile tongue depressor. The clinical research documentation needs numbers of patients. Side effects are easier contributed to the medical device with or without a direct relationship and appreciation of the patient is a correct decisive part in the evaluation. All this detailed valuation increases the certification costs.
The slow changes in hospital practices and routines is another, yet curious, reason. Interventionists take traditional biopsies on behalf of the team and only go as far as they are forced to do. Even anno 2020, they love to stick to histology and are slowly adopting the notion that molecular biology needs more representative tissue. Also, newer devices are more expensive because of the burden of regulatory requirements and premarket assessment rules, as described above. Interventionists that need to pay for the instruments and at the same time must account for side effects and complications often clash with the oncologist that receives and uses the results without taking risks and budgetary consequences. On top, reimbursement for biopsies and related imaging is, apart for the breast, poor and in several countries even absent.
Medical device distributors love to concentrate on established products, i.e. products that are already known and accepted by the medical community and do not need much time investment to present. Innovative products need budget and time, say investments, to present to physicians. Distributors in general hate to make appointments, sometimes months ahead for a simple sales visit and the challenge to explain new products in the short time that is attributed to them while visiting the physician makes them uncomfortable
The paradox in biopsy land is the increasing need for minimal invasive effective biopsy instruments with a growing biopsy market on one hand and the decreasing interest of manufacturers, vendors, distributors, and physicians in embracing new technologies. The instruments must be appropriate for the new challenges in especially oncology and regenerative medicine. The benefit of the patient is directly addressed as well as indirectly by preserving an affordable health care system. As a result, costs of recent oncology therapies will remain beyond what is affordable and per consequence, a large part of oncology patients do not get the therapy they need.
To overcome this paradoxical divergence, patients and physicians must realize that new exigences in oncology must be addressed in the right way with application of the best treatment products, application of the right tests that are performed in the best circumstances and with optimal tissue that has been taken from the patient in the most comfortable way. Every stakeholder, health care providers, physicians, industry, and patient organizations, can take responsibility in this quality process.