The future of medicine in 2037

In the post below from 2016, we wrote of what we can expect for medicine 20 years into the future. We review and revise it anew here.

An important determinant of “where medicine will be” in 2035 is the set of dynamics and forces behind healthcare delivery systems, including primarily the payment method, especially regarding reimbursement. It is clear that some form of reform in healthcare will result in a consolidation of the infrastructure paying for and managing patient populations. The infrastructure is bloated and expensive, unnecessarily adding to costs that neither the federal government nor individuals can sustain. This is not to say that I predict movement to a single payer system — that is just one perceived solution to the problem. There are far too many costs in healthcare that offer no benefits in terms of quality; indeed, such costs are a true impediment to quality. Funds that go to infrastructure (insurance companies and other intermediaries) and the demands they put on healthcare delivery work directly against quality of care. So, in the U.S., whether the Affordable Care Act (“Obamacare”) persists (most likely) or is replaced with a single payer system, state administered healthcare (exchanges) or some other as-yet-unidentified form, there will be change in how healthcare is delivered from a cost/management perspective.  -[Editor’s note: After multiple attempts by the GOP to “repeal and replace”, the strengths of Obamacare have outweighed its weaknesses in the minds of voters who have thus voiced their opinions to their representatives, many seeking reelection in 2018.]

From the clinical practice and technology side, there will be enormous changes to healthcare. Here are examples of what I see from tracking trends in clinical practice and medical technology development:

  • Cancer 5 year survival rates will, for many cancers, be well over 90%. Cancer will largely be transformed in most cases to chronic disease that can be effectively managed by surgery, immunology, chemotherapy and other interventions. Cancer and genomics, in particular, has been a lucrative study (see The Cancer Genome Atlas). Immunotherapy developments are also expected to be part of many oncology solutions. Cancer has been a tenacious foe, and remains one we will be fighting for a long time, but the fight will have changed from virtually incapacitating the patient to following protocols that keep cancer in check, if not cure/prevent it.
    [Editor’s note: Immunology has surged in a wide range of cancer-related research yielding new weapons to cure cancer or render it to routine clinical management.]
  • Diabetes Type 1 (juvenile onset) will be managed in most patients by an “artificial pancreas”, a closed loop glucometer and insulin pump that will self-regulate blood glucose levels. OR, stem cell or other cell therapies may well achieve success in restoring normal insulin production and glucose metabolism in Type 1 patients. The odds are better that a practical, affordable artificial pancreas will developed than stem or other cell therapy, but both technologies are moving aggressively and will gain dramatic successes within 20 years.

Developments in the field of the “artificial pancreas” have recently gathered considerable pace, such that, by 2035, type 1 blood glucose management may be no more onerous than a house thermostat due to the sophistication and ease-of-use made possible with the closed loop, biofeedback capabilities of the integrated glucometer, insulin pump and the algorithms that drive it, but that will not be the end of the development of better options for type 1 diabetics. Cell therapy for type 1 diabetes, which may be readily achieved by one or more of a wide variety of cellular approaches and product forms (including cell/device hybrids) may well have progressed by 2035 to become another viable alternative for type 1 diabetics. [Editor’s note: Our view of this stands, as artificial pancreases are maturing in development and reaching markets. Cell therapy still offers the most “cure-like” result, which is likely to happen within the next 20 years.]

  • Diabetes Type 2 (adult onset) will be a significant problem, governed as it is by different dynamics than Type 1. A large body of evidence will exist that shows dramatically reduced incidence of Type 2 associated with obesity management (gastric bypass, satiety drugs, etc.) that will mitigate the growing prevalence of Type 2, but research into pharmacologic or other therapies may at best achieve only modest advances. The problem will reside in the complexity of different Type 2 manifestation, the late onset of the condition in patients who are resistant to the necessary changes in lifestyle and the global epidemic that will challenge dissemination of new technologies and clinical practices to third world populations.

Despite increasing levels of attention being raised to the burden of type 2 worldwide, including all its sequellae (vascular, retinal, kidney and other diseases), the pace of growth globally in type 2 is still such that it will represent a problem and target for pharma, biotech, medical device, and other disciplines. [Editor’s note: the burden of Type 2 on people, families, communities, and governments globally should motivate policy, legislation, and other action, but global initiatives have a long way to travel.]

  • Cell therapy and tissue engineering will offer an enormous number of solutions for conditions currently treated inadequately, if at all. Below is an illustration of the range of applications currently available or in development, a list that will expand (along with successes in each) over the next 20 years.

    Cell therapy will have deeply penetrated virtually every medical specialty by 2035. Most advanced will be those that target less complex tissues: bone, muscle, skin, and select internal organ tissues (e.g., bioengineered bladder, others). However, development will have also followed the money. Currently, development and use of conventional technologies in areas like cardiology, vascular, and neurology entails high expenditure that creates enormous investment incentive that will drive steady development of cell therapy and tissue engineering over the next 20 years, with the goal of better, more long-term and/or less costly solutions.
  • Gene therapy will be an option for a majority of genetically-based diseases (especially inherited diseases) and will offer clinical options for non-inherited conditions. Advances in the analysis of inheritance and expression of genes will also enable advanced interventions to either ameliorate or actually preempt the onset of genetic disease.

    As the human genome is the engineering plans for the human body, it is a potential mother lode for the future of medicine, but it remains a complex set of plans to elucidate and exploit for the development of therapies. While genetically-based diseases may readily be addressed by gene therapies in 2035, the host of other diseases that do not have obvious genetic components will resist giving up easy gene therapy solutions. Then again, within 20 years a number of reasonable advances in understanding and intervention could open the gate to widespread “gene therapy” (in some sense) for a breadth of diseases and conditions. [Editor’s note: CRISPR and other gene-editing techniques have accelerated the pace at which practical and affordable gene-therapies will reach the market.]
  • Drug development will be dramatically more sophisticated, reducing the development time and cost while resulting in drugs that are far more clinically effective (and less prone to side effects). [Editor’s note: We are revising our optimism about drug development being more sophisticated and streamlined. To a measurable degree, “distributed processing systems” have proven far more exciting in principle than practice, since results — marketable drugs derived this way — have been scant. We remain optimistic as a result of the rapid emergence of artificial intelligence (AI) and deep learning, which have have very credible promise to impact swaths of industry, especially in medicine.]
    This arises from drug candidates being evaluated via distributed processing systems (or quantum computer systems) that can predict efficacy and side effect without need of expensive and exhaustive animal or human testing.The development of effective drugs will have been accelerated by both modeling systems and increases in our understanding of disease and trauma, including pharmacogenomics to predict drug response. It may not as readily follow that the costs will be reduced, something that may only happen as a result of policy decisions.
  • Most surgical procedures will achieve the ability to be virtually non-invasive. Natural orifice transluminal endoscopic surgery (NOTES) will enable highly sophisticated surgery without ever making an abdominal or other (external) incision. Technologies like “gamma knife” and similar will have the ability to destroy tumors or ablate pathological tissue via completely external, energy-based systems. [Editor’s note: In the late 1980s, laparoscopy revolutionized surgery for its less invasiveness. Now, NOTES procedures and external energy technologies (e.g., gamma knife) have now proven to be about as minimally invasive as medical devices can be. To be even less invasive will require development of drugs (including biotechs) that succeed as therapeutic alternatives to any kind of surgery.]

    By 2035, technologies such as these will measurably reduce inpatient stays, on a per capita basis, since a significant reason for overnight stays is the trauma requiring recovery, and eliminating trauma is a major goal and advantage of minimally invasive technologies (e.g., especially the NOTES technology platform). A wide range of other technologies (e.g., gamma knife, minimally invasive surgery/intervention, etc.) across multiple categories (device, biotech, pharma) will also have emerged and succeeded in the market by producing therapeutic benefit while minimizing or eliminating collateral damage.
  • Information technology will radically improve patient management. Very sophisticated electronic patient records will dramatically improve patient care via reduction of contraindications, predictive systems to proactively manage disease and disease risk, and greatly improve the decision-making of physicians tasked with diagnosing and treating patients.There are few technical hurdles to the advancement of information technology in medicine, but even in 2035, infotech is very likely to still be facing real hurdles in its use as a result of the reluctance in healthcare to give up legacy systems and the inertia against change, despite the benefits. [Editor’s note: Before AI and other systems will truly have an impact, IT and its policy for healthcare in the next 10 years will solve the problem of health data residing inertly behind walls that hinder efficient use of the rich, patient-specific knowledge that physicians and healthcare systems might use to improve the quality and cost of care.]
  • Personalized medicine. Perfect matches between a condition and its treatment are the goal of personalized medicine, since patient-to-patient variation can reduce the efficacy of off-the-shelf treatment. The thinking behind gender-specific joint replacement has led to custom-printed 3D implants. The use of personalized medicine will also be manifested by testing to reveal potential emerging diseases or conditions, whose symptoms may be ameliorated or prevented by intervention before onset.
  • Systems biology will underlie the biology of most future medical advances in the next 20 years. Systems biology is a discipline focused on an integrated understanding of cell biology, physiology, genetics, chemistry, and a wide range of other individual medical and scientific disciplines. It represents an implicit recognition of an organism as an embodiment of multiple, interdependent organ systems and its processes, such that both pathology and wellness are understood from the perspective of the sum total of both the problem and the impact of possible solutions.This orientation will be intrinsic to the development of medical technologies, and will increasingly be represented by clinical trials that throw a much wider and longer-term net around relevant data, staff expertise encompassing more medical/scientific disciplines, and unforeseen solutions that present themselves as a result of this approach.Other technologies being developed aggressively now will have an impact over the next twenty years, including medical/surgical robots (or even biobots), neurotechnologies to diagnose, monitor, and treat a wide range of conditions (e.g., spinal cord injury, Alzheimer’s, Parkinson’s etc.).

The breadth and depth of advances in medicine over the next 20 years will be extraordinary, since many doors have been recently opened as a result of advances in genetics, cell biology, materials science, systems biology and others — with the collective advances further stimulating both learning and new product development. 


See Reports:

Report #290, “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022.”

Report #S251, “Wound Management to 2024.”

Cardiovascular procedure volumes in the rest of the world

Cardiovascular procedures are high volume, big business in the well developed U.S, European, and Asia/Pacific markets. But much potential procedure volume has been tapped in these markets, with any appreciable growth limited to low volume, emerging procedures.

By comparison, the less-tapped “Rest of World” potential (i.e., non-U.S., non-Europe, non-Asia/Pacific) for growth is significant. Below is illustrated the 2016 size and growth to 2022 for the major cardiovascular procedures in the Rest of World.

Source: “Global Dynamics of Surgical and Interventional Cardiovascular Procedures, 2015-2022”, Report #C500 (MedMarket Diligence, LLC)

The rise and fall of medical technologies

When does one recognize that horse-and-buggy whips are in decline and auto-mobiles are on the rise?

When does one recognize that a new technology is a definite advance over established ones in the treatment of particular disease, in cost or quality?

Technologies go through life cycles.

A medical technology is introduced that is found effective in the management of a disease. Over time, the technology is improved upon marginally, but eventually a new technology, often radically different, emerges that is more effective or better (cheaper, less invasive, easier to use). It enters the market, takes market share and grows, only to be later eclipsed by a new (apologies) paradigm. Each new technology, marginal or otherwise, advances the limit of what is possible in care.

Predicting the marginal and the more radical innovation is necessary to illustrate where medicine is headed, and its impact. Many stakeholders have interest in this — insurance companies (reimbursing technologies or covering the liabilities), venture capitalists, healthcare providers, patients, and the medical technology companies themselves.

S-curves illustrate the rise in performance or demand over time for new technologies and show the timing and relative impact of newer technologies when they emerge. Importantly, the relative timing and impact of emerging technologies can be qualitatively and quantitatively predicted. Historic data is extremely useful predicting the rise and fall of specific medical technologies in specific disease treatment.

Following are two examples of diseases with multiple technologies arcing through patient demand over time.

  • Ischemic Heart Disease Past, Current, and Future Technologies
    • Open bypass
    • Percutaneous transluminal coronary angioplasty
    • Minimally invasive direct coronary artery bypass (MIDCAB)
    • Percutaneous CABG
    • Stem-cell impregnated heart patches

The treatment of ischemic heart disease, given the seriousness of the disease and its prevalence, has a long history in medicine and within the past fifty years has a remarkable timeline of innovations. Ischemia is condition in which inadequate blood flow to an area due to constriction of blood vessels from inflammation or atherosclerosis can cause cell death. In the case of cardiac ischemia, in which the coronary arteries that supply the heart itself with blood are occluded, the overall cell death can result in myocardial infarction and death.

The effort to re-establish adequate blood flow to heart muscle has evolved from highly invasive surgery in which coronary artery bypass graft (CABG) requires cutting through the patient’s sternum and other tissues to access the heart, then graft arteries and/or veins to flow to the poorly supplied tissue, to (2) minimally invasive, endoscope procedures that do not require cutting the sternum to access the heart and perform the graft and significantly improve healing times and reduced complications, to as illustrated, multiple technologies rise and fall over time with their impacts and their timing considered.

Technology S-Curves in the Management of Ischemic Heart Disease

(Note: These curves are generally for illustrative purposes only; some likely dynamics may not be well represented in the above. Also note that, in practice, demand for old technologies doesn’t cease, but declines at a rate connected to the rise of competing technologies, so after peaking, the S-curves start a descent at various rates toward zero. Also, separately note that the “PTCA” labeled curve corresponds to percutaneous transluminal coronary angioplasty, encompassing the percutaneous category of approaches to ischemic heart disease. PTCA itself has evolved from balloon angioplasty alone to the adjunctive use of stents of multiple material types with or without drug elution and even bioabsorbable stents.)
Source: MedMarket Diligence, LLC

Resulting Technology Shifts

Falling: Open surgical instrumentation, bare metal stents.
Rising and leveling: thoracoscopic instrumentation, monitors
Rising later: stem-cells, extracellular matrices, atherosclerosis-reducing drugs
Rising even later: gene therapy

The minimally invasive technologies enabled by thoracoscopy (used in MIDCAB) and catheterization pulled just about all the demand out of open coronary artery bypass grafting, though the bare metal stents used initially alongside angioplasty have also been largely replaced by drug-eluting stents, which also may be replaced by drug-eluting balloon angioplasty. Stem cells and related technologies used to deliver them will later represent new growth in treatment of ischemia, at least to some degree at the expense of catheterization (PTCA and percutaneous CABG). Eventually, gene therapy may prove able to prevent the ischemia to develop in the first place.

  • Wound Management Past, Current, and Future Technologies
    • Gauze bandages/dressings
    • Hydrogel, alginate, and antimicrobial dressings
    • Negative pressure wound therapy (NPWT)
    • Bioengineered skin substitutes
    • Growth factors

Another great example of a disease or condition treated by multiple evolving technologies over time is wound management, which has evolved from simple gauze dressings to advanced dressings, to systems like negative pressure wound therapy, hyperbaric oxygen and others, to biological growth factors to bioengineered skin and skin substitutes.

Technology S-Curves in Wound Management

Source: MedMarket Diligence, LLC (Report S254)

Resulting Technology Shifts

Falling: Traditional gauze and other simple dressings
Falling: NPWT, hyperbaric oxygen
Rising: Advanced wound dressings, bioengineered skin, growth factors

Wound management has multiple technologies concurrently available, rather than sequential (when one largely replaces the other) over time. Unsurprisingly, traditional dressings are in decline. Equipment-related technologies like NPWT and hyperbaric oxygen are on the wane as well. While wound management is not a high growth area, advanced dressings are rising due to their ability to heal wounds faster, an important factor considering that chronic, slow-healing wounds are a significant contributor to high costs. Bioengineered skin is patient-specific, characterized by faster healing and, therefore, rising.

Wound Forecast to 2026
© 2017, MedMarket Diligence, LLC.

The global dynamics of cardiovascular surgical and interventional procedures

This is an excerpt from Report #C500, “Cardiovascular Procedures to 2022.”

Cardiovascular Procedures in 2016

• Coronary artery bypass graft (CABG) surgery;
 • Coronary angioplasty and stenting;
 • Lower extremity arterial bypass surgery;
  • Percutaneous transluminal angioplasty (PTA) with and without bare metal and drug-eluting stenting;
  • Peripheral drug-coated balloon angioplasty;
  • Peripheral atherectomy;
  • Surgical and endovascular aortic aneurysm repair;
  • Vena cava filter placement
  • Endovenous ablation;
  • Mechanical venous thrombectomy;
  • Venous angioplasty and stenting;
  • Carotid endarterectomy;
  • Carotid artery stenting;
  • Cerebral thrombectomy;
  • Cerebral aneurysm and AVM surgical clipping;
  • Cerebral aneurysm and AVM coiling & flow diversion;
  • Left Atrial Appendage closure;
  • Heart valve repair and replacement surgery;
  • Transcatheter valve repair and replacement;
  • Congenital heart defect repair;
  • Percutaneous and surgical placement of temporary and permanent mechanical cardiac support devices;
  • Pacemaker implantation;
  • Implantable cardioverter defibrillator placement;
  • Cardiac resynchronization therapy device placement;
  • Standard SVT & VT ablation; and
  • Transcatheter AFib ablation

In 2016, the cumulative worldwide volume of the most prevalent cardiac surgeries and other  cardiovascular procedures (at right) is projected to approach 15.05 million surgical and transcatheter interventions. This will include:

  • in coronart artery disease, roughly 4.73 million coronary revascularization procedures via coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) or about 31.4% of the total),
  • close to 4 million percutaneous and surgical peripheral artery revascularization procedures (or 26.5% of the total);
  • about 2.12 million cardiac rhythm management procedures via implantable pulse generator placement and arrhythmia ablation (or 14.1% of the total);
  • over 1.65 million  chronic venous insufficiency, deep vein thrombosis, and pulmonary embolism targeting venous interventions (representing 11.0% of the total);
  • more than 992 thousand surgical and transcatheter heart defect repairs and  valve replacement or valve repair  (or 6.6% of the total);
  • close to 931 thousand acute stroke prophylaxis and treatment procedures (contributing 6.2% of the total);
  • over 374 thousand abdominal and thoracic aortic aneurysm endovascular and surgical repairs (or 2.5% of the total); and
  • almost 254 thousand placements of temporary and permanent mechanical cardiac support devices in bridge to recovery, bridge to transplant, and destination therapy indications (accounting for about 1.7% of total procedure volume).

During the period 2016 to 2022, the total worldwide volume of covered cardiovascular procedures is forecast to expand on average by 3.7% per annum to over 18.73 million corresponding surgeries and transcatheter interventions in the year 2022. The largest absolute gains can be expected in peripheral arterial interventions (thanks to explosive expansion in utilization of drug-coated balloons in all market geographies), followed by coronary revascularization (supported by continued strong growth in Chinese and Indian PCI utilization) and endovascular venous interventions (driven by grossly underserved patient caseloads within the same Chinese and Indian market geography).

The latter (venous) indications are also expected to register the fastest (5.1%) relative procedural growth, followed by peripheral revascularization (with 4.0% average annual advances) and aortic aneurysm repair (projected to show a 3.6% average annual expansion).

http://mediligence.com/c500/

Geographically, Asian-Pacific (APAC) market geography accounts for slightly larger share of the global CVD procedure volume than the U.S. (29.5% vs 29,3% of the total), followed by the largest Western European states (with 23.9%) and ROW geographies (with 17.3%). Because of the faster growth in all covered categories of CVD procedures, the share of APAC can be expected to increase to 33.5% of the total by the year 2022, mostly at the expense of the U.S. and Western Europe.

However, in relative per capita terms, covered APAC territories (e.g., China and India) are continuing to lag far behind developed Western states in utilization rates of therapeutic CVD interventions with roughly 1.57 procedures per million of population performed in 2015 for APAC region versus about 13.4 and 12.3 CVD interventions done per million of population in the U.S. and largest Western European countries.


Report #C500: “Global Dynamics of Surgical and Interventional Cardiovascular Procedures, 2015-2022.” Request excerpts.

This report may be purchased for immediate download at link.

Abdominal and thoracic aortic aneurysm repair: procedures forecast

Below is an excerpt from, “Global Dynamics of Surgical and Interventional Cardiovascular Procedures, 2015-2022,” (Report #C500 described, available online).

Selection of specific management protocols for patients with aortic aneurysms depends on the disease morphology as well as patient’s age, overall health status, and comorbidities involved. In cases involving smaller and relatively stable abdominal or thoracic aortic aneurysm (AAA or TAA), watchful waiting represents a commonly preferred approach. Radical surgical or endovascular interventions are generally reserved for cases when the diameter of the aneurismal sac is larger than 5cm to 5.5cm, or the annual expansion rate exceeds 1.0 cm, or when the aneurysm becomes symptomatic.

Surgical Repair of Aortic Aneurysms

Prior to the advent of AAA/TAA endovascular repair tools and techniques, a highly invasive and risky surgical repair procedure constituted the only curative option for patients with advanced and rupture prone aortic aneurysm. Conducted under the general anesthesia the procedure takes a few hours and entails a major and highly traumatic operation with a 10-15 inch cut in abdominal wall, clamping and isolation of aneurysmic segment of aorta, incision into the aneurysm, evacuation of the clot contained within, placement of a synthetic graft, and wrapping of the graft with remnants of the aortic wall.

The typical surgical aneurysm repair is associated with a substantial (5% to 8%) mortality rate and serious complications, such as stroke, myocardial infarction, renal failure etc.

Due to the close proximity to the heart, the risk and complication rates of surgical intervention for aneurysm repair on the thoracic aorta increase multifold resulting in an average procedural mortality rate of up to 30 percent.

The high cost of the procedure is largely the result of extended ICU and hospital stays, which can last upwards of a week (but average roughly 10-12 days). Further, postoperative recovery may require up to six additional weeks subsequent to discharge, making temporary disability a major consideration for many patients.

Notwithstanding these drawbacks, open surgical aortic aneurysm repair is still commonly regarded as highly effective treatment modality that virtually eliminates the risk of aneurismal sac rupture and does not require extensive postoperative follow-up exams or revisions.

However, because of high prevalence of elderly and health-impaired persons in diagnosed aortic aneurysm caseloads and traumatic nature of AAA/TAA surgery, only a fraction of the patients who could benefit from surgical aneurysm repair is deemed eligible for such a procedure.

Abdominal Aortic Aneurysm Repair with Endovascular Stent-Grafts

During the past two decades, advances in interventional technologies paved the way for the advent of a considerably less invasive and risky endovascular AAA repair procedure. The procedure involves a transcatheter deployment of the specially designed endovascular prosthesis (typically combining sealing functions of the vascular graft and full or partial stenting support structure) into a defective segment of aorta with the goal of excluding the aneurysmal sac from blood circulation.

The endovascular stent-grafts (SGs) – which come both in self-expanding or balloon-expandable versions – are typically anchored to an undamaged part of the aorta both above and below the aneurysm via a compression fit or/and with a special fixation mechanism like hooks, barbs, etc.

To accommodate a great morphological diversity of aortic aneurysms the vast majority of endovascular SGs is employing a modular design concept providing the aorto iliac, bifurcated and straight tubular device configurations to cover a variety of AAA indications. Several SG systems also feature an open stenting structure at proximal end to enable suprarenal device deployment required in about 30% to 35% of all AAA cases warranting intervention.

In its idea, the endovascular repair of abdominal aortic aneurysm was intended to produce clinical outcomes comparable to these yielded by the open surgery, while reducing the associated trauma, recovery time, morbidity and the overall treatment cost. It was also generally expected that availability of less-invasive endovascular treatment option would allow to extend caseloads coverage to sizable rupture-prone AAA patient subsets who are poor surgical candidates.

Limitations of Endovascular AAA Repair

Findings from numerous clinical studies and real-life experience in the field seem to indicate that endovascular aortic aneurysm repair via stent-graft placement tends to provide immediate procedural outcomes comparable to these obtainable with open surgery. Furthermore, the typical ICU and hospital stay for endovascular AAA repair averages 2 days (though it may last twice longer for patients with significant comorbidities). All of these translates into reduced inpatient costs of AAA repair relative to open surgery, although the high price of stent-grafting devices largely offsets these cost savings. Post-discharge recovery is also shortened from weeks or months to an average 7-10-day period.

Unfortunately, comparative long-term clinical efficacy and cost-effectiveness of the endovascular approach to aortic aneurysm repair appears to be problematic due to unavoidable shortcomings of available aortic stent-graft designs and complications associated with their less than perfect performance in situ.

The major problems associated with the endovascular AAA repair approach include relatively high incidence of endoleaks (up to 15%), endotension, and device failure, which multiply the risk of catastrophic aneurysm rupture and necessitate costly revisions (in up to 35% of the cases) as well as long-term (or life-long) patient surveillance (with mandatory imaging exams). Due to that, the actual overall cost of endovascular repair in many considerably exceeds expenses incurred in traditional open surgery.

Another limitation of endovascular stent-grafting relates to its ability to accommodate complex aortic aneurysm morphology and branch involvement. Based on some end-user and industry reporting, only about 50% of patients that develop intervention-warranting AAAs are considered good candidates for endovascular repair with currently available product configurations.

According to some recent reporting, endovascular aneurysm repair (EVAR) treatment with certain stent grafts also appears to be associated with higher late mortality rates (due to aneurysm rupture) compared to surgical AAA repair. Based on available long-term follow-up data, mortality in AAA patients retrofitted with the market-leading SG averages 1.3% and 1.5% at four and five years compared to 0.7% and 0.9% for AAA surgery.

Endovascular Repair of TAA

Introduced in Europe and the U.S. in 1998 and 2005, accordingly, endovascular techniques for aneurysm (and aortic dissection) repair on thoracic aorta represented a logical extension of the very same basic concept and technology platforms that enabled the development of AAA stent-grafts.

Because of extremely high mortality and morbidity rates associated with TAA surgery, the need for minimally invasive endovascular treatment option was even more compelling than that in AAA case.

Similar to AAA endovascular repair devices, TAA stent-grafts are intended to minimize the risk of catastrophic thoracic aortic aneurysm rupture via effective exclusion (isolation) of the aneurismal sac from blood circulation.

Unlike AAA implants, commercially available TAA stent-grafting devices feature relatively simple tubular unibody architecture with sealing cuffs (or flanges) at proximal and distal end.

Insertion of TAA SGs is done under fluoroscopic guidance via a singular femoral puncture with the use of standard transcatheter techniques. Depending on the aneurysm morphology, one or two overlapping devices might be used to ensure proper aneurismal sac isolation.

The average ICU and hospital stays and post-discharge recovery period for endovascular TAA repair procedure are generally similar to these for AAA stent-grafting intervention.

Although practical clinical experience with endovascular repair of thoracic aortic aneurysm remains somewhat limited, findings from European and U.S. clinical studies with TAA stent-grafting tend to be very encouraging. Based on these findings, stent-grafting of rupture-prone aneurysm on ascending thoracic aorta can be performed with close to perfect technical success rate yielding radical reduction in intraoperative mortality and complications compared to TAA surgery as well as impressive improvement in long-term patient survival.

Similar to AAA endografting, the main problems associated with the use of TAA SG systems include significant incidence of endoleaks and occasional device migration which require reintervention.

Aortic Aneurysm Repair Procedure Volumes

Based on the industry reporting, national and international healthcare authority data, and MedMarket Diligence estimates, in 2015, approximately 915 thousand patients worldwide were diagnosed with rupture-prone abdominal or thoracic aortic aneurysms and aortic dissections warranting radical intervention, of which roughly 359.5 thousand (or about 39.3%) were actually referred for surgical or transcatheter treatment. Covered APAC market geography (with combined population of about 2,63 billion) accounted for the largest 37.6% share of all aortic aneurysm repairs performed, followed by the U.S. with 25.6%, largest Western European states with 21.3% and the rest-of-the-world with the remaining 15.5%.

Endovascular stent-grafting techniques were utilized in approximately 162.5 thousand aortic aneurysm repair procedures in 2015, which included an estimated 133 thousand AAA-related and about 29.5 thousand TAA-related interventions (including these targeting selected thoracic aortic dissections).

The cited figures reflected a disparity both in the relative volumes of treated AAA and TAA patients and, especially, in the share of these managed with the less invasive EVAR techniques. The latter indicator was the highest for the U.S. (~75%), compared to 52% for Western Europe, 39% for APAC and only 36.6% for the ROW market geography.

During the forecast period covered in the report, the total global volume of endovascular aortic aneurysm repairs is projected to grow 5.7% per annum to approximately 243 thousand procedures, combining a 5.5% annual expansion in AAA-related interventions with a 6.6% average annual increase in TAA (aortic dissection)-related interventions.

Projected healthy gains in endovascular aortic aneurysm repair procedures should reflect continuous penetration of non-surgical (no option) AAA and TAA patient caseloads, coupled with significant incursion into surgery-eligible patient subsets both in AAA, TAA, and aortic dissection indications. Increasing reliance on utilization of less traumatic AAA and TAA stent-grafting techniques will be expedited by ongoing qualitative improvements in the endograft and delivery tools design that keep yielding more reliable, durable, versatile, and end-user friendly systems with reduced propensity to mechanical and functional failure (device kinking, fracture, endoleaks, migration, etc.) and associated clinical complications.

The largest relative gains in AAA and TAA EVAR procedures (10.9% and 11.8%, accordingly) can be expected in covered APAC territories (mostly China and India) and grossly underserved ROW zone (6.5% and 7.5%). Largely mature U.S., Western European (and Japanese) markets are likely to register a low single digit advances in utilization of endovascular AAA/TAA repair techniques.

The global procedure volume forecast for aortic aneurysm repair is presented below.

Projected Dynamics of Aortic Aneurysm Repair Procedures,
World Total, 2015-2022 (#000)

Indications / Procedures20152016201720182019202020212022CAGR 2016-2022
Total EVAR AAA/TAA Procedures1516.317.618.920.221.522.824.16.70%
Diagnosed AAA & TAA Caseloads1651701751801851901952002.80%
Treated AAA & TAA Patients5658.56163.56668.57173.53.90%
Abdominal Aortic Aneurysm (AAA) Repair
Treated AAA Patient Caseloads45474951535557593.90%
Surgical Repair Procedures33343536373839402.80%
Endovascular Repair Procedures12131415161718196.50%
Thoracic Aortic Aneurysm (TAA) Repair
Treated TAA Patient Caseloads1111.51212.51313.51414.53.90%
Surgical Repair Procedures88.28.48.68.899.29.42.30%
Endovascular Repair Procedures33.33.63.94.24.54.85.17.50%
Total Surgical AAA/TAA Repairs4142.243.444.645.84748.249.42.70%

Notes: AAA = abdominal; aortic aneurysm. EVAR = endovascular aneurysm repair. TAA = thoracic aortic aneurysm.

Source: MedMarket Diligence, LLC; Report #C500. (Full cardiovascular procedures report online.)

Source: MedMarket Diligence, LLC; Report #C500. (Full cardiovascular procedures report online.)

 

Cardiovascular procedure volume growth (interventional and surgical)

Cardiovascular surgical and interventional procedures are performed to treat conditions causing inadequate blood flow and supply of oxygen and nutrients to organs and tissues of the body. These conditions include the obstruction or deformation of arterial and venous pathways, distortion in the electrical conducting and pacing activity of the heart, and impaired pumping function of the heart muscle, or some combination of circulatory, cardiac rhythm, and myocardial disorders. Specifically, these procedures are:

  • Coronary artery bypass graft (CABG) surgery;
  • Coronary angioplasty and stenting;
  • Lower extremity arterial bypass surgery;
  • Percutaneous transluminal angioplasty (PTA) with and without bare metal and drug-eluting stenting;
  • Peripheral drug-coated balloon angioplasty;
  • Peripheral atherectomy;
  • Surgical and endovascular aortic aneurysm repair;
  • Vena cava filter placement
  • Endovenous ablation;
  • Mechanical venous thrombectomy;
  • Venous angioplasty and stenting;
  • Carotid endarterectomy;
  • Carotid artery stenting;
  • Cerebral thrombectomy;
  • Cerebral aneurysm and AVM surgical clipping;
  • Cerebral aneurysm and AVM coiling & flow diversion;
  • Left Atrial Appendage closure;
  • Heart valve repair and replacement surgery;
  • Transcatheter valve repair and replacement;
  • Congenital heart defect repair;
  • Percutaneous and surgical placement of temporary and permanent mechanical cardiac support devices;
  • Pacemaker implantation;
  • Implantable cardioverter defibrillator placement;
  • Cardiac resynchronization therapy device placement;
  • Standard SVT & VT ablation; and
  • Transcatheter AFib ablation

For 2016 to 2022, the total worldwide volume of these cardiovascular procedures is forecast to expand on average by 3.7% per year to over 18.73 million corresponding surgeries and transcatheter interventions in the year 2022. The largest absolute gains can be expected in peripheral arterial interventions (thanks to explosive expansion in utilization of drug-coated balloons in all market geographies), followed by coronary revascularization (supported by continued strong growth in Chinese and Indian PCI utilization) and endovascular venous interventions (driven by grossly underserved patient caseloads within the same Chinese and Indian market geography).

Venous indications are also expected to register the fastest (5.1%) relative procedural growth, followed by peripheral revascularization (with 4.0% average annual advances) and aortic aneurysm repair (projected to show a 3.6% average annual expansion).

Source: MedMarket Diligence, LLC; “Global Dynamics of Surgical and Interventional Cardiovascular Procedures, 2015-2022,” (Report #C500).

Geographically, Asian-Pacific (APAC) market geography accounts for slightly larger share of the global CVD procedure volume than the U.S. (29.5% vs 29,3% of the total), followed by the largest Western European states (with 23.9%) and ROW geographies (with 17.3%). Because of the faster growth in all covered categories of CVD procedures, the share of APAC can be expected to increase to 33.5% of the total by the year 2022, mostly at the expense of the U.S. and Western Europe.

However, in relative per capita terms, covered APAC territories (e.g., China and India) are continuing to lag far behind developed Western states in utilization rates of therapeutic CVD interventions with roughly 1.57 procedures per million of population performed in 2015 for APAC region versus about 13.4 and 12.3 CVD interventions done per million of population in the U.S. and largest Western European countries.

Source: MedMarket Diligence, LLC; “Global Dynamics of Surgical and Interventional Cardiovascular Procedures, 2015-2022,” (Report #C500).


Global Cardiovascular Procedures report #C500 details the current and projected surgical and interventional therapeutic procedures commonly used in the management of acute and chronic conditions affecting myocardium and vascular system.

Investment in medtech and biotech: Outlook

Medtech and biotech investment is driven by an expectation of returns, but rapid advances in technology simultaneously drive excitement for their application while increasing the uncertainty in what is needed to bring those applications in the market.

MedMarket Diligence has tracked technology developments and trends in advanced medical technologies, inclusive of medical devices and the range of other technologies — in biotech, pharma, others — that impact, drive, limit, or otherwise affect markets for the management of disease and trauma. This broader perspective on new developments and a deeper understanding of their limitations is important for a couple of reasons:

  1. Healthcare systems and payers are demanding competitive cost and outcomes for specific patient populations, irrespective of technology type — it’s the endpoint that matters. This forces medical devices into de facto competition with biotech, pharma, and others.
  2. Medical devices are becoming increasingly intelligent medical devices, combining “smart” components, human-device interfaces, integration of AI in product development and products.
  3. Medical devices are rarely just “medical devices” anymore, often integrating embedded drugs, bioresorable materials, cell therapy components, etc.
  4. Many new technologies have dramatically pushed the boundaries on what medicine can potentially accomplish, from the personalized medicine enabled by genomics, these advances have served to create bigger gaps between scientific advance and commercial reality, demanding deeper understanding of the science.

The rapid pace of technology development across all these sectors and the increasing complexity of the underlying science are factors complicating the development, regulatory approval, and market introduction of advanced technologies. The unexpected size and number of the hurdles to bring these complex technologies to the market have been responsible for investment failures, such as:

  • Theranos. Investors were too ready to believe the disruptive ideas of its founder, Elizabeth Holmes. When it became clear that data did not support the technology, the value of the company plummeted.
  • Juno Therapeutics. The Seattle-based gene therapy company lost substantial share value after three patients died on a clinical trial for the company’s cell therapy treatments that were just months away from receiving regulatory approval in the US.
  • A ZS Associates study in 2016 showed that 81% of medtech companies struggle to receive an adequate return on investment

As a result, investment in biotech took a correctional hit in 2016 to deflate overblown expectations. Medtech, for its part, has seen declining investment, especially at early stages, reflecting an aversion to uncertainty in commercialization.

Below are clinical and technology areas that we see demonstrating growth and investment opportunity, but still represent challenges for executives to navigate their remaining development and commercialization obstacles:

  • Cell therapies
    • Parkinson’s disease
    • Type I diabetes
    • Arthritis
    • Burn victims
    • Cardiovascular diseases
  • Diabetes
    • Artificial pancreas
    • Non-invasive blood glucose measurement
  • Tissue engineering and regeneration
    • 3D printed organs
  • Brain-computer and other nervous system interfaces
    • Nerve-responsive prosthetics
    • Interfaces for patients with locked-in syndrome to communicate
    • Interfaces to enable (e.g., Stentrode) paralyzed patients to control devices
  • Robotics
    • Robotics in surgery (advancing, despite costs)
    • Robotic nurses
  • Optogenetics: light modulated nerve cells and neural circuits
  • Gene therapy
    • CRISPR
  • Localized drug delivery
  • Immuno-oncology
    • Further accelerated by genomics and computational approaches
    • Immune modulators, vaccines, adoptive cell therapies (e.g., CAR-T)
  • Drug development
    • Computational approaches to accelerate the evaluation of drug candidates
    • Organ-on-a-chip technologies to decrease the cost of drug testing

Impact on investment

  • Seed stage and Series A investment in med tech is down, reflecting an aversion to early stage uncertainty.
  • Acquisitions of early stage companies, by contrast, are up, reflecting acquiring companies to gain more control over the uncertainty
  • Need for critical insight and data to ensure patient outcomes at best costs
  • Costs of development, combined with uncertainty, demand that if the idea’s upside potential is only $10 million, then it’s time to find another idea
  • While better analysis of the hurdles to commercialization of advanced innovations will support investment, many medtech and biotech companies may opt instead for growth of established technologies into emerging markets, where the uncertainty is not science-based

 

Below is illustrated the fundings by category in 2015 and 2016, which showed a consistent drop from 2015 to 2016, driven by a widely acknowledged correction in biotech investment in 2016.

*For the sake of comparing other segments, the wound fundings above exclude the $1.8 billion IPO of Convatec in 2016.

Source: Compiled by MedMarket Diligence, LLC.

 

Interventional and Surgical Cardiovascular Procedure Volumes

Cardiovascular diseases (CVDs) are a variety of acute and chronic medical conditions associated with an inability of the cardiovascular system to sustain an adequate blood flow and supply of oxygen and nutrients to organs and tissues of the body. The CVD conditions may be manifested by the obstruction or deformation of arterial and venous pathways, distortion in the electrical conducting and pacing activity of the heart, and impaired pumping function of the heart muscle, or some combination of circulatory, cardiac rhythm, and myocardial disorders.

These diseases are treated via the following surgical and interventional procedures:

  • Coronary artery bypass graft (CABG) surgery;
  • Coronary angioplasty and stenting;
  • Lower extremity arterial bypass surgery;
  • Percutaneous transluminal angioplasty (PTA) with and without bare metal and drug-eluting stenting;
  • Peripheral drug-coated balloon angioplasty;
  • Peripheral atherectomy;
  • Surgical and endovascular aortic aneurysm repair;
  • Vena cava filter placement
  • Endovenous ablation;
  • Mechanical venous thrombectomy;
  • Venous angioplasty and stenting;
  • Carotid endarterectomy;
  • Carotid artery stenting;
  • Cerebral thrombectomy;
  • Cerebral aneurysm and AVM surgical clipping;
  • Cerebral aneurysm and AVM coiling & flow diversion;
  • Left Atrial Appendage closure;
  • Heart valve repair and replacement surgery;
  • Transcatheter valve repair and replacement;
  • Congenital heart defect repair;
  • Percutaneous and surgical placement of temporary and permanent mechanical cardiac support devices;
  • Pacemaker implantation;
  • Implantable cardioverter defibrillator placement;
  • Cardiac resynchronization therapy device placement;
  • Standard SVT & VT ablation; and
  • Transcatheter AFib ablation

In 2016, the cumulative worldwide volume of these procedures is projected to approach 15.05 million surgical and transcatheter interventions. This will include:

  • roughly 4.73 million coronary revascularization procedures via CABG and PCI (or about 31.4% of the total),
  • close to 4 million percutaneous and surgical peripheral artery revascularization procedures (or 26.5% of the total);
  • about 2.12 million cardiac rhythm management procedures via implantable pulse generator placement and arrhythmia ablation (or 14.1% of the total);
  • over 1.65 million CVI, DVT, and PE targeting venous interventions (representing 11.0% of the total);
  • more than 992 thousand surgical and transcatheter heart defect repairs and valvular interventions (or 6.6% of the total);
  • close to 931 thousand acute stroke prophylaxis and treatment procedures (contributing 6.2% of the total);
  • over 374 thousand abdominal and thoracic aortic aneurysm endovascular and surgical repairs (or 2.5% of the total); and
  • almost 254 thousand placements of temporary and permanent mechanical cardiac support devices in bridge to recovery, bridge to transplant, and destination therapy indications (accounting for about 1.7% of total procedure volume).

Below is illustrated the overall global growth for each of the major categories of procedures through 2022.

Source: MedMarket Diligence, LLC; Report #C500.  (Full report available online.)

There is considerable variation in the growth of cardiovascular procedures globally, but most growth is coming out of Asia/Pacific. For example, within the area of venous interventions, the growth in the use of endovenous ablation for chronic venous insufficiency is markedly higher in Asia/Pacific than in other regions, though the U.S. will remain the largest volume of these procedures.

Source: MedMarket Diligence, LLC; Report #C500.  (Full report available online.)


“Global Dynamics of Surgical and Interventional Cardiovascular Procedures, 2015-2022” (Report #C500), published August 2016. See description, table of contents, list of exhibits at link. Available for purchase and download from link.

Forgotten Opportunities: Early Stage Biotech and Medtech Investment

Due to the uncertainty in the development, clinical testing, and regulatory approval of both biotech and medical technologies, which increasingly have to be viewed with the same competitive lens, investors have over the past few years shied away from seed stage or Series A stage company investment in favor of those nearer to market introduction. However, with the advent of a great number of new technologies and advances in the underlying science, there is enormous opportunity to identify companies and emerging sectors arising from these advances. The problem in identifying realistically promising companies is that it must be done so without falling prey to the bad investment practices in the past that ensued from a poor understanding of the technologies and their remaining commercial hurdles. Without careful consideration of remaining scientific development needed, the product’s target market, its competitors, and the sum total of the company’s capabilities to commercialize these technologies, investment in these areas will fall short of investment objectives or fail them outright.

While any of these considerations have the capacity to preempt a successful market introduction, a failure to understand the science behind the product and its remaining development hurdles to commercialization is likely to be the biggest cause of failure.

“We’ve already had one glaring example of a company, and its investors, learning the hard way that health and science advisors are important: Theranos.” (link)

Venture Capital has backed away from early stage investment

Earlier stage investment, with its higher risk, has higher potential reward, so there is a big need for more effective evaluation of potential early stage investments in order to (1) seize these opportunities that will otherwise potentially be lost with the shift to later stage fundings, (2) sort out those companies/technologies with overwhelming commercialization hurdles from those that will profitably tap an opportunity, and (3) gain the value of these opportunities before the innovation appreciates in value, driving up the price of the investment.

The Biotech Bubble

Biotech in the 1980s was enamored with companies pursuing “magic bullets” — technologies that had the potential to cure cancer or heart disease or other conditions with large, untapped or under-treated populations. With few exceptions, these all-in-one-basket efforts were only able achieve a measure of humility in the VCs who had poured volumes of money into them.

Here was evidenced a fundamental problem with biotech at a time when true scientific milestones were being reached, including successes in mapping the human genome: Landmark scientific milestones do not equate with commercial success.

As a result, money fled from biotech as few products could make it to market due to persistent development and FDA hurdles. By the late 1980s, many biotechs saw three quarters of their value disappear.

A Renewed Bubble?

The status of biomedical science and technology, with multiple synergistic developments, will lead to wild speculation and investment, potentially leading to yet another investment bubble. However, there will be advances that can point to real timelines for market introduction that will support investment.

Recent advances, developments and trends supporting emerging therapeutics

  1. Stem cells. A double-edged sword in that these do represent some the biggest therapeutics that will emerge, yet caution is advised since the mechanisms to control stem cells are not always sufficient to prevent their nasty tendency to become carcinogenic.
  2. Drug discovery models, such as using human “organoids” and other cell-based models to test or screen new drugs.
  3. Systems to accelerate the rapid evaluation of hundreds, perhaps, thousands of potential drugs before moving to animal models or preclinicals.
    1. Machine-learning algorithms
    2. Cell/tissue/organ models
    3. Meta-analysis, the practice of analyzing multiple, independently produced clinical data to draw conclusions from the broader dataset.
  4. Cross-discipline science
    1. cell biologists, immunologists, molecular biologists and others have a better understanding of pathology and therapeutics as a result of information sharing; plus BIG DATA (e.g., as part of the “Cancer Moonshot”). Thought leaders have called for collection and harnessing of patient data on a large scale and centralized for use in evaluating treatments for specific patients and cancer types.
    2. Artificial intelligence applied to diagnosis and prescribed therapeutics (e.g., IBM Watson).
    3. Examples of resulting therapies, at a minimum, include multimodal treatment – e.g., radiotherapy and immunotherapy – but more often may be represented in considerably more backend research and testing to identify and develop products with greater specificity, greater efficacy, and lowered risk of complications.
  5. Materials science developments, selected examples:
    1. Scaffolds in tissue engineering
    2. Microgels
    3. Graphene
    4. Polyhedral boranes
    5. Nanometric imprinting on fiber
    6. Knitted muscles to provide power link
    7. 3-D printed skin and more complex organs to come
    8. Orthopedic scaffolds made from electrospun nanofibers
  6. CAR-T (chimeric antigen receptor T cell therapy)
  7. CRISPR/Cas-9. Gene editing
    1. Removal, insertion of individual genes responsible for disease
    2. Potential use for creating chimeras of human and other (e.g., pig) species in order to, for example, use pigs for growing human organs for transplant.
  8. Smart devices: smart biopsy needles, surgical probes to detect cancer margins, artificial pancreas. Devices using information

 

We sum this up with these prerequisites for investment:

Prerequisites for Early Stage Med/Bio Investment

  1. A fully understood and managed gap between scientific advance and commercial reality.
    1. Investment must be tied to specific steps (prototyping, preclinicals, clinicals, physician training, etc.).
  2. A management team qualified in commercializing medtech or biotech products.
    1. CEOs (and/or Chief Medical Officers, Chief Scientific Officers) with medical science backgrounds (MD, PhD) favored over CPAs or even JDs.
  3. Reimbursement strategy pursued as something more than an afterthought
  4. Technology development in sync with end-user acceptance and training to leverage the benefits:
    1. Easier to use
    2. Fewer complications
    3. Attractive physician revenue streams
  5. Broad competitive advantage pursued:
    1. Product benefits must stand up against all competition, irrespective of technology type (devices competing with drugs, biotech).
    2. Benefits of reducing the cost of care for an existing patient population are paramount.
    3. Competitive advantage must consider the trend in technology development to avoid being disrupted by other products soon to reach the market.
  6. Predefined exit strategy; selected examples:
    1. Positioning to add innovation to a mid-cap or large-cap medtech or biotech as acquirers.
    2. Development of platform technologies for licensing or sale.
    3. IPO

 

Future investments are likely to track the historical focus on specific diseases and conditions:

Source: MedMarket Diligence, LLC and Emerging Therapeutic Company Investment and Deal Trends; Biotechnology Innovation Organization.


MedMarket Diligence, mediligence.com, tracks medical and biotechnology development to provide meaningful insights for manufacturers, investors, and other stakeholders.

Coronary revascularization options evolve

The number of options that are in use or development for coronary revascularization or other treatment for ischemic heart disease is extraordinary. Given the mortality associated with coronary artery disease, it is unsurprising that it has been the focus of so much development.

Below are the options that have evolved for treatment of ischemic heart disease, inclusive of surgical, interventional, and other medical approaches.

Coronary Revascularization and Other
Ischemic Heart Treatment Options

Source: MedMarket Diligence, LLC

See also “Global Dynamics of Surgical and Interventional Cardiovascular Procedures, 2015-2022”, report #C500. Order online.