Dr. Lockwood, Editor-in-Chief, is Dean of the Morsani College of Medicine and Senior Vice President of USF Health, University of South Florida, Tampa. He can be reached at DrLockwood@ubm.com.

Charles J. Lockwood, MD, MHCM

’s founding Editor-in-Chief, Dr. John Queenan, to join its Editorial Board. It was an unexpected honor and just a bit intimidating given that the Board was a veritable “who’s who” of ob/gyn greats.  I quickly realized that the twin pillars of the magazine’s success were John’s inspirational leadership and the quality, sagacity, and editorial independence of that board. For 25 years, Dr. Queenan had been a master at picking the 

 board members who, in turn, identified key topics, emerging trends and outstanding authors. John led their deliberations, added his own prescient ideas and, of course, crafted truly memorable editorials.

The next year, I was stunned when John asked me to become 

’s second Editor-in-Chief. I have enjoyed my time in this post immensely. Fortunately, I strictly followed John’s “recipe” by assembling a great board, a number of whom have been with me since the start, including Drs. Joe Leigh Simpson, Paula Adams Hillard, and Sharon Phelan. I was blessed to be able to add other leaders in the field including my old friends Joshua Copel from Yale, one of the true greats in obstetrical ultrasound, and Sarah Kilpatrick, Chair of Obstetrics and Gynecology at Cedars-Sinai in Los Angeles and an expert in medical complications of pregnancy. Newer friends joined including Drs. John Delancey, a pioneer and leader in urogynecology; Ilana Cass, a brilliant gynecologic oncologist and now Chair of the Department  of Obstetrics & Gynecology at Dartmouth; Chris Pettker, a leader in the patient safety movement from Yale; and Steve Ory, a master clinician and reproductive endocrinologist from Florida International University in Miami. I was also lucky enough to recruit Dr. Jon Einarsson, an international authority in minimally invasive gynecological surgery from Harvard, as Deputy Editor. What great success the magazine has enjoyed over the past two decades is largely due to these wonderful folks as well as their predecessors, including giants like Drs. Leon Speroff and Ed Wallach. 

Perhaps the most daunting task over the past two decades has been coming up with ideas for editorials. Some concepts were obvious, like telling the story of 9/11 from the perspective of my patients at NYU and Bellevue Hospital. Others were inspired by the recurrent professional liability crisis, onerous new government regulations, political threats to women’s reproductive health, rapidly changing healthcare financing, physician burnout, and the challenges of residency training. However, most reflected bread and butter clinical topics including the safety of vaginal breech deliveries and trials of labor after prior cesareans, the causes of maternal mortality and preterm birth, the appropriate use of antenatal corticosteroids, misoprostol and low molecular weight heparin, and screening for thrombophilias, genetic disorders, Group B 

 and gestational diabetes. Gyn topics included postmenopausal hormone therapy, new contraceptives, screening for cervical cancer, and the need to encourage human papillomavirus vaccination. While I have not shied away from controversial topics, I have also tried to tell stories from the perspective of busy clinicians. 

Click here to read some of Dr. Lockwood's editorials

And I have been honored to receive a number of national publishing awards for these editorials, including three prestigious Jesse H. Neal Awards from the American Society of Business Publication Editors, as well as two Gold Awards for Editorials and an Award in the Editorial/Editor’s Letter category from the American Society of Healthcare Publication Editors. My approach to writing has been simple: find a topic I was interested in or passionate about, critically review all relevant literature, and then sit down and write. I do hope my editorials have helped shape ob/gyn practice in positive ways. I have certainly enjoyed hearing from readers, who have not been shy about providing feedback in person, by phone, by e-mails, through formal letters to the editor, and more recently, via social media.  

It is hard to imagine it’s been 20 years. I have truly enjoyed every minute. But this seems like a propitious time to pass the Editor-in-Chief “baton” to someone from the next generation of ob/gyn leaders who can provide a different perspective and their own passion. Over the next few months, the magazine will select a new leader and I am sure they can maintain 

’s extraordinary success over the past 45 years if they also follow John Queenan’s tried and true formula. 

In closing, I want to thank our dedicated, brilliant, and very witty past and present editorial board members. I am also incredibly grateful to my terrific managing editors, including Judy Orvos, Paul Cerrato, Susan Olmstead, and Linda Wetzel, whose professionalism and sage counsel have been invaluable. Finally, I want to thank our wonderful readers, who were my inspiration.

Articles

After 20 years as editor-in-chief, Dr. Lockwood announces that he has stepped down and reflects on his time with the magazine.

A fond farewell

If you find yourself on a mountain or at a lake this summer with those rarest of modern gifts-peace, solitude, and the chance for a few days of uninterrupted reading-I recommend Tom Friedman’s 

 It is vintage Friedman with the meticulously researched reportage expected from a three-time Pulitzer Prize winner. The book addresses three of the weightiest subjects of our time: the simultaneous acceleration of information technology, economic globalization, and climate change. While these three challenges ought to matter to every human on the planet, they have special resonance for ob/gyns because globally their impacts fall disproportionately on women and because women hold a key to the planet’s ability to overcome their collective threat.
	 


	While these three forces seem suddenly upon us, climate change reflects centuries of industrialization. On the other hand, the explosion in computing power and economic globalization have emerged over decades. In fact, most of the critical components of the latter two forces date back to one year – 2007.

 That year the iPhone and Android operating system were introduced, AT&T invested in a massive expansion in software-enabled networks setting the stage for logarithmic increases in wireless traffic, and IBM’s Watson was created giving birth to the dawn of artificial intelligence (AI). Also, in 2007, Kindle was rolled out by Amazon, and Airbnb was conceived. Twitter, LinkedIn and Facebook all started around that year using software developed by a company called Hadoop that generated software algorithms allowing hundreds of thousands of computers to function as one. In biotech, 2007 saw leveraging of this raw computational power to begin to dramatically reduce the cost and unimaginably increase the speed of DNA sequencing. Interestingly, that was also the year that experimental proof of CRISPR was reported.

 Thus, “infotech” and “biotech” are inextricably linked. All these changes accelerated economic globalization disrupting traditional markets in goods and services (including healthcare), labor and capital. 


	Moore’s law states that the speed and capacity of computing doubles every 2 years in parallel to the number of transistors that can be placed on a microchip. To illustrate this geometric expansion, Friedman notes that compared to its first-generation microchip, Intel’s sixth-generation chip has 3,000 times the performance and 90,000 times the energy efficiency at 60,000 times lower cost. The acceleration in information technology has also been made possible by startling advances in collectively developed open-source software (e.g., GitHub) and development of seamlessly interactive application programming interfaces (APIs). These APIs are the programming commands that allow you to save and send files, connect various web applications, buy stuff on-line, make apps, and permit individual computers to be networked – basically they make the Web the Web. Moreover, investments in ultra-fast transmission fiberoptic cabling coupled with introduction of 

 (CDMA) software to exponentially increase wireless capacity have allowed unprecedented and previously unimaginable levels of connectivity. 

The “cloud,” a vast network of computers spread across the globe, now stores, accesses, and shares data and permits software and services to run directly off the Internet, further amplifying acceleration of information technologies. Simultaneously, there have been dramatic improvements in computer sensors from cameras to detectors of motion, water pressure, energy consumption, engine performance, traffic congestion, temperature, global positioning, etc., all of which can broadcast their data, leading to the “Internet of things” and permitting both preventive and prescriptive maintenance (i.e., letting you know when a device will fail). In health care the Internet of things will generate 1 million GB of personal health information for each patient in her lifetime, which is equivalent to about 300 million books.

All these advances have vastly amplified the flow of data while reducing the complexity and cost of accessing it and accelerating the potential power of AI. One consequence for physicians is that a primary care doctor would need 630 hours per month just to keep up with the explosion of new literature.

 However, this accelerated flow of information affects all professions, contributing to the pervasive burnout being experienced across society.


	Friedman’s second great acceleration is globalization of the economy. Access to abundant and nearly free flows of information has led to many disruptive business innovations from Amazon, Lyft and Uber to Airbnb, all of which have displaced workers and whole industries across the planet. I recently received a harangue from a taxi driver in Nashville about the evils of Uber and what it had done to his income. While I sympathized with his plight, I realized he might as well be howling at the moon. Self-service whether it’s to create legal contracts, complete tax returns, book hotel and airline flights, or conduct real estate transactions has disrupted all those industries. Your iPhone is quickly replacing credit cards, and blockchain-derived currencies like Bitcoin may soon replace cash. Physicians will not be immune from this revolution. Wait till telehealth and facilitated self-service Internet-based medicine drive the provision of health care to the lowest bidder and soon we may be howling at the moon as well.

Access to abundant and free information also allows innovative start-ups to blossom from anywhere in the world where someone has sufficient training, a computer, and access to the Internet.

 Friedman notes that Massive Open Online Courses (MOOCs) are allowing poor students in rural India take some of the most advanced IT courses offered by top US colleges. Even manufacturers now crowdsource across the globe to optimize designs for new products. All this is fueling acceleration of the globalized economy. And restricting immigration will not limit the spread of innovative business disruption delivered via a new app developed by a creator in Turkey or Turkmenistan. Friedman points out that in 2014, $30 trillion in goods, services, and capital-equal to nearly 40% of the planet’s gross domestic product-crossed national borders, a 6-fold increase from 1990. And that does not begin to measure the impact of the free flow of information around the world. Tariffs may raise costs but are unlikely to stop that flow! 


	Freidman’s third great acceleration is climate change. The atmosphere now has 400 parts per million (ppm) of carbon dioxide, which is 50 ppm above the limit needed to prevent catastrophic global warming. Biodiversity is diminishing as deforestation has reduced the earth’s original forests to 62% while most climate scientists believe we cannot afford to dip below 75%. Pesticides and fertilizers are creating toxic algae blooms while ocean acidification is destroying our coral reefs and native fish populations. Desertification is a major threat to sub-Saharan Africa and drought is leading to crop failure in Central America. Climate change is also harming global health by driving alterations in vector ecology including expansion of pathogens such as malaria and Lyme disease, and arboviruses such as chikungunya, dengue, Zika, and West Nile. Additional adverse health effects accrue related reductions in drinking water quality, air pollution, and heat-related illnesses. 

Friedman also notes, ironically, that improved global health measures have reduced infant mortality, fueling population increases in impoverished lands already unable to fully feed, educate or employ their current populations. Overpopulation leads to over-farming, deforestation, and a growing scarcity of fresh water, which in turn worsen climate change. For example, Niger’s population in 1950 was 2.5 million, in 2016 it was 19 million, and by 2050 it is predicted to be 72 million, while the planet will have 9.7 billion inhabitants. 

Why adapting to change is so difficult for humans


	Since 2007, the pace of change in information technologies, economic globalization and climate change have all accelerated beyond Homo Sapiens’ ability to adjust their educational structures, economies, energy consumption, government regulations, and social safety nets to accommodate to them. Friedman argues that while technology platforms turn over every 5 to 7 years, it takes 10 to 15 years for humans to adapt to these new technologies. And this maladaptation is far greater in under-resourced countries that are also the most adversely impacted by climate change, leading to further impoverishment, famines, and mass migrations of primarily young men northward into Europe and North America.

 Thus, in these under-resourced areas it is women who are left behind on failing farms, often with no education and with elderly relatives and many young mouths to feed. Increasingly, though, women and children are contributing to the refugee crisis, exacerbating the adverse public health consequences of associated violence, accidents, inadequate nutrition, and lack of medical care. 


	So how do Americans and the citizens of industrialized nations cope with the disruptive impact of information technologies and a globalized economy? For example, how do ob/gyns and other physicians adjust to an era when medical knowledge doubles every 73 days such that between the start of medical school and the end of residency training, students will experienced three doublings of medical knowledge?7 The strategy is the same for physicians and plumbers. To remain viable in this new workplace, everyone must embrace lifelong learning by transforming AI into IA – which includes intelligent assistance and intelligent assistants.  

Friedman suggests that intelligent assistance is a way for government, employers, and, I would add, universities and academic health centers to provide powerful online learning tools to facilitate lifelong learning. New companies are already filling this niche (e.g., Udacity, edX, Coursera, Khan Academy) and LinkedIn has assembled a large repertoire of mini-courses to assist lifelong learning. Universities are offering MOOCs while medical schools and hospitals are expanding their professional development programs and simulation centers. For our part, 

 monitors current women’s health reports and pushes out summaries in our weekly e-newsletter while assembling various resource centers containing curated reviews. 

Intelligent assistants consist of the AI interface between humans and the tools they need to complete a job. (Think of a Da Vinci robot blocking you from ligating a ureter). In medicine, intelligent assistants could also consist of an electronic health record with AI-stoked decision support providing just-in-time and point-of-care access to relevant data needed to precisely choose the correct diagnostic test or prescribe the optimal personalized medication. It could also include AI-empowered search engines that not only search what you query but know what you don’t know and should be searching.

 Of course, when search engines decide what you should know, should do and should think, we will have even bigger problems! 

But what about the vast majority of the globe’s population who do not live in industrialized nations or worse, reside in failed states like Syria where chaos holds sway? It has been estimated that 4.5 billion people are either urban or rural poor. As noted, these parts of the globe are most affected by climate change and overpopulation, which is promoting collapse of their agriculture. They also have substandard educational systems, limited web access, and inchoate manufacturing sectors. This leaves millions of disaffected young men (and some young women) prone to join drug gangs, guerrilla groups or jihadists. While addressing climate change should be the planet’s top priority, Friedman suggests that in the short run we should focus on three simple remedies. The first is planting trees across sub-Saharan Africa to slow desertification (“the Great Green Wall”). The second is providing chickens to desperately poor families because chickens require minimal resources to maintain and can serve as both a source of protein-rich nutrition and modest income. But perhaps the best hope for these countries to escape the effects of the three “accelerations” is increased access to high-quality education for women. This will enhance economic development and help break the cycle of violence generated by disaffected young men who fall prey to irrational ideologies. Education should also help increase access to and use of contraception so desperately needed to break the cycle of poverty in under-resourced nations. 


	We live in the age of acceleration. Advances in information technology occur at a pace exceeding the human mind’s ability to adapt. This, in turn, is fueling acceleration of economic globalization and both trends are disrupting traditional employment models. Economic privation and climate change are also accelerating mass refugee migrations from under-resourced countries and failed states to Europe and North America fueling a toxic cycle of extremism, violence, and nativism. But humans created all three of these accelerations and if we embrace empiricism, rationality, and evidenced-based policies while eschewing baseless ideologies, mysticism, and fear, we have the power to mitigate their adverse impacts. In addition to addressing climate change by thoughtfully but expeditiously transitioning to renewable energy sources and promoting “reforestation”, we need to address accelerating technological complexity and economic globalization by embracing lifelong learning achieved through converting AI to IA. We must also pursue a global commitment to educating all the world’s women and providing universal access to contraception. 

We have the power to mitigate the adverse impact of rapid advancement in information technology.

Coping in the age of acceleration

Almost 25% of women with breast cancer have a family history of the disease, and women with an affected first-degree relative have a 1.75-fold higher risk of developing cancer.

That risk increases to 2.5-fold with two or more affected first-degree relatives. Multiple genes have been identified that are associated with breast cancer. While 

 have received much attention as they are linked to 20% to 25% of hereditary breast cancers and 5% to 10% of all breast cancers, 6 genetic testing has expanded to include 28 genes. The above table

presents the National Comprehensive Cancer Network (

) guidelines for genetic testing. Genetic counselors can be a good referral source, should there be a need for genetic testing. If no genetic counselor is available in your area, then referral to a breast surgeon is appropriate to discuss family history as well as a patient’s lifetime risk of breast cancer and need for genetic testing.

			For more information on breast health: 

Almost 25% of women with breast cancer have a family history of the disease and, those who do have a higher risk of developing cancer.

NCCN guidelines for genetic testing 

USPSTF and ASCCP recommend cytology screening every 3 years from ages 21 to 29

From ages 30 to 64, screening can be cytologic every 3 years or cytology with high-risk HPV testing every 5 years (co-testing) 

Pap testing can be discontinued at age 65 for those who have had previous negative smears

The same Pap smear screening guidelines should be followed in women who had the HPV vaccine

Women under 21 may need testing for STIs but that does not include a Pap smear or HPV testing

Key points for today’s ‘well-woman’ exam: A guide for ob/gyns

CDC recommends HIV testing all patients aged 13 to 64 

Testing should be performed annually on high-risk patients

High-risk populations include injection-drug users and their sex partners, individuals who exchange sex for money or drugs, sex partners of HIV-infected individuals, and heterosexuals if they or their sex partners have had ≥ 1 sex partner since their most recent HIV test

Annual testing for chlamydia and gonorrhea is recommended in sexually active women < 25, and those older who have a new partner, multiple partners or a partner with a STD

Type-specific HSV testing should be considered in patients who present for STI evaluation 

Hepatitis C testing should be done on women born between 1945 and 1965 and patients who are at high risk, including individuals on immunosuppressive therapy or hemodialysis or who are HIV-positive

ACS recommends screening average-risk patients at age 45 

Options include colonoscopy every 10 years, computed tomographic colonography or sigmoidoscopy every 5 years, take-home high-sensitivity guaiac-based FOBT or FIT annually, and multitargeted stool-DNA testing every 3 years 

A positive result on a non-colonoscopy test should trigger colonoscopy 

USPSTF recommends mammography every 2 years for women > 50

USPSTF does not recommend biannual screening for women aged 40 to 49 but ACP does

For high-risk women, ACS recommends annual screening with mammography and MRI beginning at age 30 

ACP recommends mammography every 2 years in patients with life expectancy ≥ 10 years

After age 75, according to ACP, the decision to continue screening should be based on a patient’s health status

ACP recommends limiting use of MRI to patients at high risk or to determine disease extent after diagnosis

The AHA-approved cut-off for diagnosis of hypertension is now 130/80 mg/Hg

The risk calculator (cvriskcalculator.com) should be used instead of LDL levels to determine whether use of statins is warranted

To determine need for statins in patients with a 10-year risk of 5% to 20%, coronary artery calcium scoring is recommended by the Society for Cardiovascular Computed Tomography

Screening for diabetes should be done after pregnancy and in patients who have hypertension, hyperlipidemia or obesity (aged 40-70)

For patients aged ≥ 45, a baseline fasting blood sugar and repeat screening at least every 3 years thereafter are recommended

Annual screening is recommended for patients who are overweight or have risk factors for diabetes

BMD should be performed in women > 65 with no risk factors for osteoporosis

Follow-up testing should be done every 2 to 5 years, depending on risk

 should be used to evaluate 10-year risk of fracture 

As more patients turn to ob/gyns for wellness exams, physicians need to stay up-to-date on current recommendations.

The 'well-woman' screening guidelines

 on this topic, I reviewed the principal reasons why prescription medications in this country are so costly. I pointed out that the “market” in prescription drugs is grossly distorted by opaque pricing, costly intermediaries, price inelasticity and a lack of consumer control as well as manufacturer rebates, direct-to-consumer advertising and co-pay coupons. I also noted that brand drug makers are free to set their own prices, which in the case of specialty drugs can be astronomical (e.g., spending on just 

To make matters worse, when patents expire, manufacturers can delay conversion of their costly brand drugs to less expensive generics through “product hopping” and “ever-greening.” But even after generic transitions occur, limited competition frequently permits generic manufacturers to achieve effective monopolies, sustaining high prices. Well-intentioned government regulations (e.g., 

) designed to promote innovation have had disastrous unintended consequences for drug prices. Medicare’s inability to negotiate drug prices or import inexpensive foreign drugs also drive up costs. And then there are the financial incentives that drug companies dangle in front of physicians to prescribe high-cost medications. While the sheer complexity of the problem is daunting, there are simple steps that the Federal government could take to restrain prescription drug costs without restraining the extraordinary innovation that is the hallmark of the US pharmaceutical industry (Table 1).
	 

Many stakeholders from the National Academy of Medicine (

) to the Trump Administration have advocated for greater transparency in the various financial flows and profit margins within the drug supply chain (e.g., manufacturers, pharmacy benefit managers [PBMs], and retail, wholesale and 340 B-eligible hospital pharmacies).

 For example, a patient goes to her pharmacy to pick up a prescription drug and, if the drug is covered by an insurer, likely has a co-pay. Subsequently the manufacturer sends a rebate to the PBM hired by the patient’s insurer to negotiate prices. The PBM, after retaining some of the rebate, passes the remainder on to the insurer, which often uses it to offset premium costs to retain customers. This incentivizes higher drug costs since patients will potentially pay exorbitant sums for a drug their physician says they need but manufacturers’ rebates go to intermediaries and not to the patient. Worse, all these transactions are cloaked in secrecy in the name of market competition. 

Requiring drug makers to publish their prices and rebates would expose the true costs of intermediaries and likely exert downward pressure on pricing due to improved market efficiency. The NAM has proposed that the Department of Health and Human Services (HHS) obtain, curate, and publicly report drug pricing data (e.g., list prices, rebates, discounts, net prices) on a quarterly basis, conduct analyses of these data, and inform the Food and Drug Administration (

 Beyond the “dog shaming” impact of such reporting on drug pricing, this would likely fuel meaningful antitrust actions to enhance market efficiency. 

In a more radical disintermediation step, this January, 

 rules to require manufacturers to pass discounts directly to Medicare patients at the pharmacy counter rather than indirectly, through rebates to intermediaries like PBMs.

 Currently Medicare patients are not eligible for manufacturers’ patient assistance plans because of federal kick-back restrictions but perversely, rebates to intermediaries are allowed. While this proposal holds great promise for reducing individual patient drug costs and seems inherently more just, it does risk increasing Part D premiums and reducing pressure to switch to generic or biosimilar specialty drugs.

 Similarly, Congress should eliminate the Medicaid drug rebate program, which discourages drug makers from discounting drug costs to any payer since it would increase the cost of their rebate to Medicaid.   

Reform Federal regulations that are driving up drug prices


	The Trump administration has accelerated FDA approval of generic drugs with over 1000 new approvals in 2017 potentially saving $9 billion.

 Moreover, it is seeking to close loopholes used by brand drug makers to restrain generic competition. More importantly, HHS is seeking authority to increase Medicare’s ability to negotiate drug prices. These actions deserve robust bipartisan support. I believe strongly that there is an urgent need to apply the full weight of US government drug purchasing power to negotiate drug prices for both Medicare and Medicaid and create a national formulary like those used by most other industrialized nations. 

There is need to reform the Orphan Drug Act of 1983.

 First, financial incentives for prevention and treatment of rare diseases should not be extended to widely sold generic drugs (e.g., 17-hydroxyprogesterone caproate). Second, reducing the patient number threshold defining an “orphan” disease from less than 200,000 to a more reasonable number (e.g., 30,000) would have an immediate beneficial effect on costs. I would also advocate ending the 

, which was designed to bring grandfathered medications under stricter control but has resulted in substantially higher prices, on average 37% higher, and frequent drug shortages.

Other simple regulatory actions with potentially major economic benefits include having the FDA permit reduced-dose medication vial size, encourage utilization of multiuse vials, and significantly extend the recommended shelf lives of medications to decrease wastage. The latter is particularly egregious as the designated shelf life of drugs is often not evidence-based and frequently grossly underestimated.

Finally, we need Tort reform. Drug companies should be liable only for known or predictable harms purposefully not disclosed during an FDA review, and not for rare harms undetectable during Phase 1 to 3 clinical trials. Reducing such liability costs could have a demonstrable effect on drug pricing.

Because foreign governments effectively negotiate with US drug makers for lower prices and many of the components of U.S. medications are manufactured abroad, there is an inherent logic to allowing drug importation. The FDA has pointed out drugs manufactured in a foreign country for the US market are produced in FDA-registered plants that also make drugs sold (at far lower prices) in other countries, an implicit indicator of drug safety.

 However, there are risks to unrestrained importation. A substantial number of drugs imported via the Internet have been reported to be less effective or ineffective and/or to contain impurities or toxins.

 Thus, FDA oversight would be needed for any such program, which would add costs. Califf and Slavitt have argued that when market distortions exist leading to drug shortages or high prices, the FDA should use its authority to support importation.

This seems like a very reasonable middle ground.

Control unscrupulous manufacturing practices

There is no doubt that direct-to-consumer (DTC) advertising works or we would not be flooded with the vast number of ads we see on television touting high-cost specialty drugs that clear skin, prevent clots, or permit quicker recovery from chemotherapy. Most come with the offer of a manufacturers’ patient assistance plan or co-pay coupons (if commercially insured) which reduces patient out-of-pocket expenses for costly brand drugs but also reduces use of inexpensive generic drugs by 60%.

 While First Amendment protections likely make it impossible to ban such advertising, Congress should eliminate the tax deductibility of DTC advertising and an industry code of conduct should be adopted for such marketing. Similarly, Congress should require mandatory disclosure of industry support for not-for-profit patient advocacy groups, which are often heavily subsidized by drug makers to promote their products.

 Finally, it should tighten restrictions on drug detailing visits and inducements to MDs.

Institute value-based payment for medications


	Health care financing is evolving from a fee-for-service system that incents volume to a value-based payment (VBP) system that rewards better outcome for lower costs. Prescription drug pricing should also be based on a VBP paradigm.

 Pricing of brand medications should consider the high development costs and substantial financial risks manufacturers incur to bring new drugs to market (e.g., 90% of new drugs fail to reach market approval). Indeed, patent protections permit exclusivity to sell novel drugs as a hedge against such development risks, but such exclusivity should not be a license for unrestrained pricing. Rather, brand drug pricing should also be based on value-effects of a drug on actual outcomes (e.g., survival, improved function, and quality of life years added) over cost. A drug’s impact on aggregate health costs (e.g., need for hospitalizations, surgery, multiple medications, rehabilitation, and nursing home care) should also be considered in price determinations. While these measurements are complex and require time to calculate, the 

 should help fund federal agencies that can make such calculations. In the end, VBP for drugs is likely the most effective way of restraining medication costs without restraining innovation.
	 

America should be justifiably proud of the incredible discoveries and innovative therapies that its pharmaceutical industry has produced, often in concert with medical school researchers. However, prescription drug costs in this country are far too high and rising at many multiples of the rate of inflation. These costs threaten the financial viability of Medicare, Medicaid and indeed, our entire health system. Our system also burdens American families with high out-of-pocket costs. There are many causes of this crisis, including an opaque and distorted pharmaceutical market, perverse government regulations, unscrupulous marketing techniques, and a failure to leverage the federal government’s vast negotiating leverage. Fortunately, there are some very straightforward steps that can be taken to lower costs without impeding innovation. These include measures to increase price transparency to restore market forces, reform of well-meaning Federal regulations whose unintended consequences are paradoxically inflating drug prices, eliminating or at least restraining unscrupulous marketing practices, and ultimately transitioning to a VBP system for medications. 

1. Dana KN, Hertig JB, Weber RJ. Drug pricing transparency: the new retail revolution. 

2. Augustine NR, Madhavan G, Nass SJ (editors) National Academies of Sciences, Engineering, and Medicine. 2018. Making medicines affordable: A national imperative. Washington, DC: The National Academies Press. 

3. US Department of Health and Human Services. American patients first: The Trump administration blueprint to lower drug prices and reduce out-of-pocket costs. 

4. Gellad WF, Ennis M, Kuza CC. A new safe harbor - turning drug rebates into discounts in Medicare Part D. 

5. Gupta R, Dhruva SS, Fox ER, Ross JS. The FDA Unapproved Drugs Initiative: an observational study of the consequences for drug prices and shortages in the United States. 

6. Allen M. The myth of drug expiration dates. ProPublica. https://www.propublica.org/article/the-myth-of-drug-expiration-dates Accessed May 26, 2019. 

7. Horvath JC, Anderson GF. The states as important laboratories for Federal prescription drug cost-containment efforts. 

8. Blackstone EA, Fuhr JP Jr, Pociask S. The health and economic effects of counterfeit drugs. 

9. Califf RM, Slavitt A. lowering cost and increasing access to drugs without jeopardizing innovation. 

In the second part of this series, potential solutions to fix the rising drug cost problem are examined.

Ensuring medications are more affordable without stifling innovation (Part 2) 

By now you have likely seen advertisements by the pharmaceutical industry criticizing Trump administration proposals to reduce the high cost of prescription drugs using various strategies that include linking the price that Medicare pays for drugs to that paid by other industrialized countries.

 In my own state, a modest proposal by the Governor to permit importation of Canadian medications has been met by grim commercials claiming this action would open a flood gate of deadly “contaminated” Chinese drugs. Many of these attack ads remind me of those used to try to block the Obama administration’s Affordable Care Act. When an industry attacks both liberal and conservative policy proposals aimed at restraining health care costs, it is worth carefully examining the issues. 

The US pharmaceutical industry is responsible for bringing to market many truly extraordinary drugs that are revolutionizing treatment of common and rare (so-called orphan) diseases but the cost of prescription drugs is bankrupting families and threatening the solvency of both public and private health care financing systems. The first half of this two-part editorial looks at the challenges posed by the high cost of brand-name drugs and the reasons for those numbers. Part two, in a future issue, will review market-based solutions and improved regulatory policies that can make prescription drugs more affordable without stifling innovation. 

In case you missed it: How likely are adolescents to fill antibiotic prescriptions for STIs?

Economic burden of high medication costs 

 was $3.5 trillion or $10,739 per person and consumed 17.9% of our Gross Domestic Product (GDP).

 That is twice as much as the average of the next nine highest-spending nations.

 To place this into context, if we could reduce health care expenditures to 10% of GDP, we would recoup enough money to pay for the country’s entire primary and secondary education system, twice our current defense budget or three times what we spend on public transportation and highways.

 Annual expenditures on pharmaceuticals now account for $500 billion or about 16.7% of total US health care spending and costs for branded drugs are increasing at an unsustainable 15% per year.

 Among the 11 highest income nations, the United States has the highest pharmaceutical spending per capita at $1443 compared with a mean of $749 for all 11 countries, with brand medications accounting for almost all our excess spending.

 In the United States, brand medications represent about 10% of prescriptions but 75% of costs.

 reported that 62% of respondents took at least one prescription drug and 24% took four or more.

 Of the latter, 29% had either not filled prescriptions, skipped doses or taken an over-the-counter drug instead of a prescribed one because of cost and 58% spent more than $100 per month for prescriptions. And although manufacturers of brand and generic drugs are in a high-risk business, their net profit margins are 28% and 18%, respectively, placing them second and fourth in profitability, respectively, among 26 major industrial sectors.

Normally the market for commercial products operates in a predictable manner with price reflecting supply and demand curves and intense competition enhancing the value of products. Moreover, consumers generally have access to accurate, understandable, and readily available information about product quality and price. In efficient markets, rational price equilibria are established among producers, wholesalers, retailers, and consumers. But medications are not a rational market (Figure 1). In contrast to traditional markets, in which consumers are the primary decision-makers, patients have little say over prescription drug purchases. Physicians generally determine which drugs are prescribed bound only by the occasional and appealable payor formulary. But most physicians have 

 knowledge of what a patient will actually pay for a drug.

Next, supply chain intermediaries (i.e., wholesale and retail pharmacies, pharmacy benefit managers, and payers) engage in a complex set of opaque transactions with manufacturers and/or among themselves to set prices. Resultant rebates and discounts permit skimming of profits that together account for 41% of medication costs.

 Pharmacy benefit managers (PBMs) are supposed to negotiate prices and establish formularies to reduce costs for private insurers and self-insured large employers. But many PBMs operate their own mail-order and retail pharmacies and receive rebates from manufacturers that are not passed on to insurers, employers or patients. Worse, PBM payment algorithms are often linked to the dollar value of the drugs provided (i.e., the higher the price, the more the profit). While PBMs now cover 85% of patients with prescription drug insurance coverage, three PBMs have 73% market share, which allows them to extract greater discounts from manufacturers while retaining more of the savings.

Direct-to-consumer (DTC) marketing also drives up the cost of brand drugs. Because of the complexity of pharmacokinetics, drug interactions, etc., most nations do not permit DTC marketing of drugs. In fact, the United States is one of only two nations in the world (New Zealand is the other) that permits DTC drug advertising.

 In 2015, $5.2 billion was spent on DTC advertising of prescription drugs, the majority on television ads and all of it tax deductible as a business expense.

 Another marketing ploy is the common use of manufacturer rebates or co-pay coupons to encourage patients to accept, request, and occasionally demand high-priced specialty drugs rather than cheaper generics. These coupons selectively increase brand drug sales by 60%.

 Pharmaceutical advertisements and drug representative “detailing” in physician offices are designed to influence physician prescribing patterns. Currently, nine out of 10 drug companies spend more on marketing than on research and development.

Have you read - Study: 1 in 7 antibiotic scripts may be unnecessary

Also unique among other nations, US drug makers are free to set the price of their drugs without government constraints. Specialty drugs (like the ones you see commonly advertised on TV for psoriasis and Crohn’s disease) account for 2% of prescriptions but 33% of drug spending.

 Biogen’s Spinraza, an anti-sense oligonucleotide to treat spinal muscular atrophy, was initially priced at $750,000 in the first year and $375,000 annually thereafter.

, a gene therapy for retinal disease caused by homozygosity for RPE65 gene mutations, was initially priced at $850,000 while Novartis’ Kymriah, a chimeric antigen receptor T cell (CAR T) treatment for refractory B-cell precursor acute lymphoblastic leukemia, costs $475,000.

 While it’s hard to contest the benefits of these agents if you or a family member are affected by such serious diseases, their costs appear exorbitant. 

Beyond the factors itemized above, medication prices are also inflated by perverse government regulations, prohibitions against drug importation, the inability of Medicare to negotiate drug prices, brand drug makers’ suppression of generic competition, price gouging by generic drug manufacturers, and conflicts of interest accruing direct payments to physicians by industry. 

Perverse effects of government regulations

The Orphan Drug Act of 1983 was designed to encourage development of treatments for rare diseases (i.e., affecting fewer than 200,000 patients/year).

 Since then, about 600 “orphan’ drugs have been approved with approvals accelerating over the past few years. Benefits to companies whose agents are approved under this pathway include an additional 7 years of exclusivity, expedited processing, reduced clinical trial size, and tax credits for development. Despite these advantages or perhaps because of them, the average orphan drug price is 5.5-fold higher than other agents and by 2020, orphan drugs will account for 21% of brand drug sales or $209 billion. Among the top 100 US drugs, orphan drug costs per year were $140,443 vs. $27,756 for non-orphan drugs.

It is important to bear in mind that many of these orphan drugs are generics that are simply repurposed. Obstetricians will recall that in 2011, the US Food and Drug Administration (FDA) approved exclusive manufacture of 17-hydroxyprogesterone caproate by K-V Pharmaceuticals for 7 years under the Orphan Drug Act and while the compounded version cost $200 per pregnancy, the company initially priced their version at $11,000 per pregnancy.

Yet another well-meaning but perversely applied regulation is the 2006 FDA Unapproved Drug Initiative, designed to bring grandfathered medications (i.e., those that entered the market before the FDA’s 1938 enabling legislation) in line with modern standards. Gynecologists may recall that in 2014, the FDA approved vasopressin for hypotension using this law and Par Pharmaceuticals was given exclusive rights to manufacture this 100-year-old drug. Its price quickly soared from $4 to $138 per vial, a 3,141% increase, triggering acute shortages.

 Other drugs with prices and availability similarly adversely impacted by this Act include epinephrine, ephedrine, colchicine, potassium chloride, and neostigmine. The latter an 80-year-old drug saw its price increase from $3.25 to $80.50 per vial!

Absence of regulation also poses a challenge. Other nations directly negotiate with drug makers to lower costs. In contrast, Medicare makes coverage determinations based on whether a drug is “necessary and reasonable” not on its costs for Parts A & B, which account for about 40% of Medicare drug costs. While Medicare Part D plans can negotiate prices, they use PBMs and have only 20% lower costs.

 Worse yet, because other nations aggressively negotiate drug prices, many US drug makers sell products outside this country at variable cost but charge Americans a premium to cover fixed, variable, and other costs and to generate hefty profits. Allowing drug imports would create a global market instead of compelling US consumers to subsidize other nations’ drug costs. While the Health and Human Services Secretary has had discretion to allow certain imports since 2000, this has never been done. But permitting drug imports is not a panacea because other countries might limit exports to prevent shortages and price increases. Moreover, drug makers could penalize exporting countries (e.g., in 2004, GlaxoSmithKline and Pfizer threatened to limit sales of their drugs to Canadian pharmacies that resold them in the United States).

Suppression of generic competition and generic market distortions

The ability of generic drug manufacturers to compete with brand drug makers can have a dramatic effect on drug prices. On average, the transition to generic status reduces a drug’s cost by 70%.

 However, while generics represent 90% of prescriptions, they account for only 25% of drug costs. Brand drug makers seek to delay the transition to generics by engaging in “product hopping,” the practice of slightly modifying existing drug formulas to obtain new patents and then “ever-greening,” extending exclusivity by removing the original drug from the market. For example, since the 1980s, 

drug makers have tweaked versions of insulin

 that act for either a short or long duration, patenting these innovations along the way such that there are no current generic versions.

 This strategy has led to high prices, large profits, and acute shortages of insulin. 

Brand drug makers can also deny potential generic competitors access to their patented drugs for comparison studies required by the FDA to establish equivalence. Some brand drug makers pay potential generic drug makers to delay production, so called “pay-to-delay” or, as noted, incentivize patients to buy higher-priced brand drugs instead of generics through co-pay coupons. 

But even after a brand drug goes off-patent and generic competition begins, distortions in the market can lead to price gouging. FDA backlogs and high regulatory costs can delay and/or limit other generic drug competitors from entering the market, creating monopolies and drug shortages. The Government Accounting Office (GAO) reports that more than 50% of generic drugs are now produced by a single company.

 Where competition exists, price fixing may occur with the GAO reporting 315 instances of generic drug price increases of more than 100%, and 48 of 1,411 drugs increasing price 500% or more in 1 year. As a result, shortages have occurred among commonly used generic drugs such as heparin, doxycycline, methotrexate, and various cardiac drugs. Forty-five states and Washington, D.C. have filed lawsuits against 18 companies alleging collusion to fix prices on 15 generic medicines.

These market distortions in generic prices have received much media attention. Many readers will remember Martin Shkreli, the CEO of Turing Pharmaceuticals. He 

, a 62-year-old drug used to treat toxoplasmosis in AIDS patients by 5,000%, from $13.50 to $750 per tablet.

 Mylan hiked the price of its EpiPen two-pack from $160 to $600 (with $300 going to a PBM).

 Rodelis Therapeutics bought rights to the tuberculosis drug cycloserine and bumped its price from $500 to $10,800 for 30 capsules.

 While such egregious price increases have received much notoriety, public awareness has not attenuated the practice.

More from Dr. Lockwood: ‘Policing’ pregnant women during the opioid epidemic

 authorized by the Physicians Payment Sunshine Act requires industry to disclose all payments to physicians.

$2.82 billion in general (non-research) payments were made to physicians

 While that figure includes over $1 billion for invention-related royalties and licensing fees, it also includes nearly $500 million in consulting fees, $237 million for food and beverages, and $188 million for travel and lodging. In addition, eight out of 10 patient advocacy groups, which often lobby for a specific drug or device, receive financial support from Pharma which they are not obligated to report.

Industry made 517,077 non-research payments, valued at $80 million to 23,292 (49.7%) ob/gyns between August 1, 2013 and December 31, 2015.

 Subspecialists received larger median payments than generalists ($500 vs. $296); urogynecologists received the largest median dollar amount, maternal-fetal medicine physicians the least. Median payments to ob/gyn subspecialists exceeded payments to orthopedic surgeons, although the latter remain the biggest recipients of overall payments, primarily from royalties or licenses. By contrast, the most common (94%) payments to ob/gyns were for food and beverages, entertainment, and travel.

The extent to which rising drug costs are adversely impacting our economy and threatening the viability of our health care system seems clear. There are many drivers of escalating drug prices, including absence of a true market, high costs of intermediaries, unscrupulous marketing practices, and suppression of generic competition by brand drug makers. Other cost drivers include perverse incentives engendered by flawed government regulations and the inability of Medicare to negotiate drug prices or to permit drug importation. Finally, long-standing symbiotic financial relationships between physicians and drug makers adds yet another layer of incremental costs. While the sheer magnitude of these challenges is daunting, the good news is that there are also many practicable steps that can be taken to enhance medication affordability while preserving the extraordinary level of innovation that the US pharmaceutical industry has achieved. In Part 2 of this editorial, I will describe these solutions. 

American Patients First: The Trump Administration Blueprint to Lower Drug Prices and Reduce Out-of-Pocket Costs https://www.hhs.gov/sites/default/files/AmericanPatientsFirst.pdf  Accessed 4/20/2019

CMS.gov National Health Expenditure Fact Sheet 

https://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-reports/nationalhealthexpenddata/nhe-fact-sheet.html

Augustine NR, Madhavan G, Nass SJ (editors) National Academies of Sciences, Engineering, and Medicine. 2018. Making medicines affordable: A national imperative. Washington, DC: The National Academies Press. 

Papanicolas I, Woskie LR, Jha AK. Health care spending in the United States and other high-income countries. 

. 2018 Mar 13;319(10):1024-1039. Erratum in: 

Henry J. Kaiser Family Foundation. Public opinion on prescription drugs and their prices. Published March 1, 2019. 

https://www.kff.org/slideshow/public-opinion-on-prescription-drugs-and-their-prices/

National Public Radio. Drug puts a $750,000 “price tag on life” August 1, 2017 https://www.npr.org/sections/health-shots/2017/08/01/540100976/drug-puts-a-750-000-price-tag-on-life; Accessed 4/20/2019

CNBC A US drugmaker offers to cure rare blindness for $850,000 Jan. 3, 2018 

https://www.cnbc.com/2018/01/03/spark-therapeutics-luxturna-gene-therapy-will-cost-about-850000.html

Fried I, Beam AL, Kohane IS, Palmer NP. Utilization, cost, and outcome of branded vs compounded 17-alpha hydroxyprogesterone caproate in prevention of preterm birth. 

Hakim A, Gupta R, Ross JS. High costs of FDA approval for formerly unapproved marketed drugs. 

Business Insider. Why a lifesaving drug that’s been around since 1923 is still unaffordable.

 https://www.businessinsider.com/why-is-there-no-generic-insulin-for-diabetes-2016-8

The New York Times. Big price increase for tuberculosis drug is rescinded. Sept. 21, 2015. 

https://www.nytimes.com/2015/09/22/business/big-price-increase-for-tb-drug-is-rescinded.html

Policy & Medicine. Open Payments Data 2017: Significant drop in number of payments. 

The economic impact of drug costs and how we got here are examined in the first of a two-part series.