“People don’t trust private health insurance companies for all the right reasons.”
– Senator Bernie Sanders.
Throughout the world, industrialized nations look at the USA and are befuddled by
its opioid crisis. Between 1999 and 2011, we witnessed the number of opioid deaths
in the USA increase from 4,030 to 16,917,1 with these figures having seemingly stabilized
over the past several years.2 Many agree regarding the root causes of the crisis,
with an analysis by Webster et al3 identifying health comorbidities (most prominently
substance use disorders), payer policies mandating methadone as a first-line treatment
option, physician error due to a lack of knowledge, patient nonadherence, unanticipated
medical and mental health issues, concomitant utilization of other central nervous
system depressants such as benzodiazepines, and sleep-disordered breathing as contributory.
One contributor to the opioid crisis that Webster et al3 failed to discuss was fraudulent
marketing regarding the safety of certain opioid analgesics. For example, while Purdue
Pharma claimed that the risk of addiction to its original formulation of OxyContin®
was less than 1%,4 in 2008 alone, the number of new nonmedical users of OxyContin
aged 12 years or older was estimated at half a million.5 This is not to suggest that
all nonmedical users are addicted or that other opioid analgesics have not been inappropriately
promoted, but rather that Purdue Pharma’s biased promotion of OxyContin was certainly
the most visible and publicized of such marketing efforts.
Much has been done over the past several years in order to mitigate the opioid crisis
in the USA. Some of the measures that have been taken appear to have been effective,
while others have been ineffectual. Some, we posit, have actually been blatantly harmful
to patients with pain, and, accordingly, to society.
One such measure has been prescription drug monitoring programs (PDMPs), which have
been either implemented or passed into law in every state other than Missouri.6 However,
data indicate that in most states, use of PDMPs by providers is “rare”, and accordingly,
PDMPs cannot be considered to be efficacious in their current forms.7
Another tactic to stem the tide of opioid overdoses and deaths has been state legislation
that requires all patients receiving opioids to sign “treatment agreements”. For example,
the state of Indiana passed a law late in 2013 requiring that such agreements are
signed by all patients receiving opioids outside of palliative care settings for more
than 3 consecutive days.8 “Treatment agreements”, also known as “opioid agreements”
and “opioid contracts”, have been considered part of “universal precautions” since
the seminal paper by Gourlay et al was published in 2005.9 However, there is no evidence
that an agreement has had any effect on stifling opioid abuse; furthermore, addicted
people are likely to agree to sign anything if it results in access to their substance(s)
of abuse.
Urine drug testing is also a part of universal precautions that has its advocates10
and, more recently, its detractors.11 Unfortunately, while urine drug testing makes
a considerable degree of common sense, the empirical evidence regarding its efficacy
in reducing prescription opioid abuse is limited, as determined by systematic reviews.12,13
Many also believe that improving physician understanding of the potential dangers
of opioid analgesics is an effective means of reducing opioid aberrancy, overdoses,
and deaths.14 Some have opined that improving physician education regarding the overall
treatment of pain is likely to be helpful.15 This may be true, although there is a
dearth of empirical data supporting even mandatory pain continuing medical education’s
positive impact on opioid prescribing patterns. It has been noted that mandatory pain
medical education regarding opioids fails to address the real causes of prescription
opioid abuse,16 and until states with mandatory pain continuing medical continuing
education requirements are able to empirically establish that they save lives, the
impact of their efforts remains presumptive.
Another nonempirically-based approach to solving the prescription opioid abuse and
overdose problem in the USA has been state policy and systems-level interventions
pertaining to what constitutes “appropriate” dosages of opioids. A recent review17
of such approaches concluded that while such efforts are important, the data supporting
them are “limited and inconsistent”. The authors of the review note the importance
of improving the evidence bases, requiring improvements before such approaches are
considered a requisite for making broad policy and practice decisions based upon them.
Among such interventions are state-mandated efforts to limit the amounts of opioids
prescribed, often in terms of a morphine-equivalent daily dosage. A review of opioid
guidelines18 indicates considerable disagreement regarding upper dosing thresholds,
with none of thresholds in any way evidence-based. Although a study in Washington
State19 determined that the risk of overdose increased with higher dosages of opioid
analgesics, most overdoses occurred at low to moderate dosages, as these are the dosages
most likely to be prescribed. While some of the authors of the Washington State opioid
dosing guideline that went into effect in 2007 noted the temporal contiguity between
the implementation of the guideline and the state’s decrease in prescription opioid
mortality,20,21 they fail to mention that the guideline was written in a manner that
had a clear “chilling effect” on providers and hospital systems – scaring them into
abandoning opioid therapy altogether as an aspect of their pain management armamentaria.22
Beyond the 2007 guidelines, in 2010 Washington State proceeded to pass an even harsher
law dictating how physicians can treat pain, with that law going into effect in 2011.
While Franklin et al23 reported in 2013 that only a small percentage of providers
had discontinued prescribing opioids for chronic noncancer pain, anecdotal reports
within the clinical practice of the first author (MES) suggest that the actual figure
is considerably higher.
We believe that most of these efforts to reduce prescription drug abuse are well intended
and suspect they may have prevented overdose deaths and diversion, although measuring
their efficacies as stand-alone strategies or as elements of a coordinated risk evaluation
and management strategy is likely impossible. We propose another measure for more
sustained, serious consideration. For a number of years, the pharmaceutical industry
has understood that producing opioids in tamper-resistant/abuse-deterrent formulations
(TR/ADFs) could potentially reduce their abuse and associated overdoses and deaths.
There is evidence that these formulations may work to reduce real-world abuse. In
the 1970s, addicts learned that pentazocine, when mixed with an antihistamine and
injected, produced euphoria similar to that associated with heroin. Sterling-Winthrop
responded by creating and receiving US Food and Drug Administration (FDA) approval
for a pentazocine-naloxone combination product, thereby developing the first ADF in
1982. Emergency room visits associated with pentazocine decreased rapidly.24 In 2010,
Purdue Pharma voluntarily reformulated its extended-release oxycodone product, the
drug most commonly associated with abuse and the opioid crisis.25 Initially, they
were not permitted to market it as an ADF due to a lack of research supporting the
claim.26 However, the subsequent research supporting its efficacy as an ADF has been
compelling,27–30 and its approval by the FDA as the first opioid permitted to be labeled
as an ADF was granted in 2013.31 Although Purdue Pharma’s generous research budget
has made their oxycodone ADF the most heavily investigated in terms of efficacy for
deterring abuse, support of TRFs of other opioid analgesics is also beginning to appear
in the literature.32–34 As TR/ADFs are proving effective in reducing opioid abuse
and mortality, it has been suggested that all TR/ADFs are granted Schedule III status,
while all non-TR/ADFs are provided with Schedule II status as a rational response
to the opioid scheduling conundrum.35
The availability of TR/ADFs to significantly attenuate the US opioid crisis is not
part of the agenda of the health insurance industry, the sole focus of which is on
cost-containment and profitability. Schatman et al have written extensively regarding
the role of the health insurance industry in perpetuating suboptimal pain care in
the USA by refusing to cover interdisciplinary treatment programs, and the ethical
implications of this decision.36–43 Despite their extremely strong evidence bases
for clinical efficacy44–47 and empirical data supporting their cost-efficiency,48,49
the number of such programs in the USA has decreased from over 1,000 in 199950 to
fewer than 100 today outside the Veterans Administration.51 Not surprisingly, in nations
where citizens’ health and well-being are considered the responsibility of the government,
the number of interdisciplinary pain programs has been growing steadily.51 It may
not be a coincidence that the opioid crisis in the USA began at about the same time
that the number of interdisciplinary programs began to precipitously decrease. Poitras
noted that the change in general pain management practices during this period resulted
in “a substantial and predictable impact on the available supply of prescription opioids
available for diversion”.52 One of the great benefits of interdisciplinary pain treatment
programs is that their goals and outcomes include cessation of, or at least reduction
in, opioid analgesic utilization.53–56
Part of the US opioid crisis was related to private and public insurers’ decisions
to designate methadone as a first-line drug for chronic pain, based only upon its
extremely low cost.3 This insurance industry policy accompanied the involvement of
methadone in approximately one third of all fatal prescription opioid deaths between
the years 1999 and 2010, despite the drug representing only 5% of all opioids prescribed
(or 9% based on 2010 data).57 We hope that with the release of the American Pain Society
Methadone Safety Guidelines58 and an American Academy of Pain Medicine position paper59
last year that identified methadone’s lack of efficacy in treating chronic pain and
the established safety issues, methadone prescriptions for chronic pain will dramatically
decrease. Irrespective, insurers can be expected to continue to look for ways to contain
the costs associated with treating patients with chronic pain, with dollars taking
precedence over regard to individual or societal well-being.
The costs of research and development of TR/ADFs are staggering, as is the case with
many types of drugs. Given the opioid crisis, the FDA is particularly stringent in
regard to the requirements for established safety and efficacy of all opioid products.60
Accordingly, TR/ADFs are expensive. A number of authors have written about insurance
carriers’ unwillingness to cover TR/ADFs,61–63 with Brushwood et al64 expressing concern
that a patient may require documentation of risk of abuse or even a diagnosis of addiction
in order to receive third-party coverage. Indeed, a review of a cross-section of formularies65
determined that the reformulated continuous-release oxycodone is often excluded from
private insurance formularies, irrespective of its strong empirical support for abuse
deterrence. It is important to note that research has indicated that insurance carriers
were reluctant to pay for the more expensive OxyContin even prior to its reformulation
for enhanced safety, resulting in increased use and abuse of less expensive and more
dangerous opioids.66 Ben-Joseph et al67 recently determined that access limitations
of a pre-ADF and post-ADF formulation of an opioid due to prior authorization and
tier change (ie, assigning more expensive medications higher co-pays) restrictions
resulted in increased overall medical costs without any offset savings in pharmacy
costs. Beyond the empirical findings, anecdotal reports of insurers’ refusal to cover
TR/ADFs abound. This has become particularly problematic in instances where physicians
who are concerned with patient safety (and perhaps the integrity of their own practices)
refuse to prescribe any opioids other than TR/ADFs. As is so often the case, the cost-containment
and profitability “ethic” of the insurance industry results in unnecessary patient
suffering, either through oligoanalgesia or individuals at high risk for aberrancy
being prescribed less safe opioids.
Not only do TR/ADFs potentially save lives, but economic costs to society as well.
Kirson et al68 recently determined that the annual societal cost savings associated
with the oxycodone ADF in the USA include annual medical cost savings of $430 million
and indirect societal savings of $605 million annually, totaling over $1 billion in
savings per year. Their analysis did not include savings associated with the numerous
other TRFs currently on the market, although it can be assumed that they, too, have
resulted in substantial societal savings. As TR/ADFs are less “desirable” or “likable”
among abusers69,70 they become less likely to be diverted. This is of great significance
as research indicates that diversion accounts for as many as 63% of fatal prescription
medication overdoses.71
In regard to TR/ADFs, Katz et al72 suggested that “Formulary controls that limit reimbursement
can help ensure that higher risk opioids are not prescribed unless the risks outweigh
the benefits”. The question becomes, however, “risk to whom?” The insurance industry’s
frequent refusal to cover TR/ADFs is not particularly “risky” within their own profit-driven
contexts. The data suggesting that approval of TR/ADFs would result in savings for
insurers68 is ignored in many instances, illustrating that the health insurance industry
is “penny wise and pound foolish”. However, there exists another possible explanation
for this self-defeating behavior – one that would also explain insurers’ increasing
refusal to pay for cost-effective interdisciplinary pain management programs. The
insurance industry is aware of the data indicating that the average enrollee will
switch insurance carriers every few years.73 Accordingly, their seemingly nonsensical
policy of refusal to cover TR/ADFs may be more shrewdly calculated than appears on
the surface. The extreme expense of paying for the treatment of prescription opioid
abuse is certainly no secret, with a recent study indicating that tampering with opioid
analgesics results in substantial increases in health care use.74 However, given the
frequency with which enrollees switch carriers, it is quite possible that insurers
are willing to take the chance that the next carrier will be forced to “pick up the
pieces” of abuse and addiction. Given the substantial expense associated with treating
chronic pain,75 would the insurer’s bottom line not improve if these “expensive” enrollees
were to simply expire?
Some states are trying to rein in the sole focus on profits. In the past several years,
a small handful of states have passed legislation prohibiting insurers from engaging
in “fail first” policies. These policies have encouraged the dispensing of generic
(and in the case of opioids, non-TR/ADFs) medications even if the physician has stipulated
that the patient should receive a branded medication. Nayak and Pearson76 have suggested
that more than other cost-containment strategies, “fail first” policies result in
significant ethical concerns. While these limited state actions should be commended,
this egregious insurance industry practice continues in all but the eight states that
have enacted legislation prohibiting or severely limiting this maleficent policy.77
In summary, in the interests of cost-containment and profitability, the health insurance
industry has contributed to the opioid crisis in the USA by refusing to pay for therapies
to reduce the harm associated with opioid prescribing. A better way to marry cost-containment
with societal well-being is to support progressively safer delivery systems for the
opioid analgesics that remain a crucial component of pain physicians’ treatment armamentaria.
Federal agencies such as the FDA and the Drug Enforcement Administration claim to
have an interest in stemming the tide of opioid abuse. Perhaps it is time for the
federal government to require health insurance carriers (including Medicare and Medicaid)
to provide coverage for the opioid formulations that have the potential to substantially
ameliorate the nation’s persisting prescription opioid crisis.