Best Practices in Managed Substance Use Disorder Treatment

Best Practices in Managed Substance Use Disorder Treatment

In the United States, an estimated 22 million people live with a substance use disorder. Despite their prevalence, substance use disorders continue to go untreated: many individuals forgo help for addiction because of the surrounding stigma, while providers often lack the training to properly recognize and diagnose them. Even with a diagnosis, individuals still face fragmented treatment for these chronic conditions and a high rate of relapse. Without the proper supports, recovery can often seem impossible.

At Beacon Health Options (Beacon), recovery from substance use is not only possible—it’s expected. As today’s leading partner for helping people live healthier, more productive lives, Beacon provides superior clinical management for mental health and substance use disorders, a strong employee assistance program, specialty programs for autism and depression, and data- driven analytics to improve the delivery of care.
With more than 30 years of experience in managed care, we understand the unique challenges of addiction. Managing effective, evidence-based programs nationally and across all lines of business, we provide the right tools and resources to identify and treat substance use disorders and help individuals achieve and sustain long-term recovery. Beacon’s proven model of substance use disorder care management relies on seven core features:

1. Development and Management of a High Quality Continuum of Care

We maintain a continuum of care to ensure members receive the right kind of support and setting for the fluctuating intensity of their needs. Our national network spans every state and encompasses all levels of care, from inpatient detoxi cation programs to intensive outpatient rehabilitation and community-based support services, so members can move to a less restrictive setting as soon as their condition improves while remaining in a safe and therapeutic environment. Ultimately, our goal is to transition members into localized settings to access community-based care, support and resources and prevent unnecessary hospitalization.

We maintain strong partnerships with the substance use disorder provider community along the continuum of care. For example, we pay an enhanced rate for Structured Outpatient Addiction Program (SOAP) providers who use Motivational Interviewing or have an af liation with a homeless shelter. Our staff are also often recruited from the provider community—coming from a diverse array of programs and treatment backgrounds, including acute, residential, and outpatient levels of care—and help to ensure positive connections with the substance use disorder provider community across the entire service continuum.

2. Standardization of Screenings and Assessments

Despite their prevalence, substance use disorders frequently go undiagnosed and untreated. This can largely be attributed to individuals’ reluctance to seek help for these conditions due to the surrounding stigma of addiction, as well as a lack of provider training to properly recognize and diagnose these conditions. To help promote earlier engagement and improved outcomes for members, we use empirically validated screening tools to target substance use disorders when they are more manageable. And with more than a third of all mental health care in the U.S. now being performed by primary care doctors, we ensure these tools are readily available to providers in primary and community-based settings.

One of the ways we help medical providers identify individuals who may be at risk for developing a substance use disorder is through Screening, Brief Intervention and Referral to Treatment (SBIRT), a screening tool speci cally designed to target the larger population exhibiting harmful behaviors but not clinically substance-dependent. After undergoing a universal screening, individuals at risk for developing a substance use disorder receive an educational intervention to change their behavior, and, if appropriate, a referral for more extensive assessment or treatment. And because of its standardized provider training and screening guidelines, SBIRT can be administered in nearly every type of health care setting, including primary care, dental of ces, community health centers, and HIV clinics.

3. Endorsement of Uniform Medical Necessity Criteria

To ensure that treatment is effectively managed and that members receive the appropriate level of care, Beacon uses evidence-based medical necessity criteria, which guides decisions around service intensity, treatment setting, need for continuing care, and readiness for discharge. Beacon’s medical necessity criteria for treating substance disorders is based on the ASAM Criteria, a collection of clinical guidelines developed by the American Society of Addiction Medicine (ASAM) and the most widely used set of criteria in the United States for the treatment of substance use issues. The ASAM criteria takes into consideration the comprehensive needs of the member, including strengths, challenges, goals, and life areas. These objective standards establish a spectrum of services which members can move between based on their changing clinical needs, while also identifying the least intensive treatment services a member needs to recover.

The ASAM criteria individualizes treatment times so that members are not limited to a xed number of treatment days. By tailoring our medical necessity criteria to this multi-dimensional approach, Beacon can reunify the system of care, and connect members to the right services at the right time while meeting their unique and comprehensive needs. And to ensure we remain consistent with current clinical best practice, Beacon’s Corporate Executive Medical Management Committee and Company Quality Control review our medical necessity criteria at least annually.

4. Promotion and Adoption of Evidence-Based Services

To produce better outcomes for the treatment of substance use disorders, we promote systematic, evidence-based services developed by established experts in the eld. These programs include:

  • Medication-Assisted Treatment (MAT): As the nation’s opioid crisis continues to grow, Beacon promotes the use of supervised medication in combination with counseling and behavioral therapies to treat the whole person. Beacon’s approach includes real-time support for prescribers, such as an expert staffed support hotline for those treating substance use disorders. By improving access to resources for medication self- management, we can connect more people to the help they need to recover.
  • Structured Outpatient Addiction Program (SOAP): In Massachusetts, we incorporate SOAPs—short-term, structured, clinically intensive group-oriented treatment services— to individuals returning to the community from medically managed detoxification or acute treatment programs, or to individuals needing more intensive treatment than other outpatient programs may provide. We also endorse programs supported by Substance Abuse and Mental Health Services Administration’s (SAMHSA) National Registry of Evidence Based Programs and Practices, including:
  • Matrix Model: Developed through 20 years of experience in real-world treatment settings, the Matrix Model is an intensive, 16-week outpatient treatment approach consisting of relapse-prevention groups, education groups, social-support groups, individual counseling, and urine and breath testing. The program is guided by a therapist, and includes education for loved ones affected by substance use disorders.
  • Motivational Interviewing: We implement focused and goal-oriented Motivational Interviewing (MI) to help people recognize and change their high-risk behavior, and based on the individual’s goals, develop an action plan. Through incorporating MI counseling into their initial intake/orientation session, community-based substance abuse treatment clinics can also improve program retention.
  • Wellness Recovery Action Plan (WRAP): A self-management intervention, WRAP teaches participants how to implement the key concepts of recovery into their everyday lives, and helps them identify their personalized wellness resources in order to make an individualized plan to manage their disorder.

5. Easing the Administrative Burden

To help providers take the focus off of cumbersome administrative tasks and enhance member experience, we offer easy-to-use online assessments, medical necessity determinations, authorizations, and claiming at no cost to the provider. Our streamlined system makes routine tasks such as processing claims, obtaining claims information, and verifying eligibility status easy and convenient. Providers may also receive quick technical assistance by contacting our Help Desk.

We also offer webinars on a quarterly basis for providers and their key staff to learn more information on our various system enhancements, as well as program and administrative updates.

6. Support for Recovery through Peer Services and Long-Term Chronic Care Management

Beacon understands that treating substance use disorders is a continuous process—in fact, the National Institute on Drug Abuse (NIDA) reports that the relapse rate for drug addiction is 40 to 60 percent. Because we recognize the challenges associated with substance relapse, we offer long-term support for substance use disorders based on the principles of recovery and resiliency as we work to return people to their communities.


Beacon’s Peer Services offer members collaborative support through persons who have lived with substance use disorders and reached a significant level of recovery. Our trained Peer Support Specialists offer ongoing assistance and education as members reintegrate back into the community, helping members learn problem-solving skills and other strategies to help them achieve and sustain recovery. Peer Support Specialists can also help members identify and connect with community-based resources to support their unique ongoing needs.


Our chronic care management addresses the comprehensive needs of members with substance use conditions and helps them transition back into the community by addressing their holistic needs. Our approach promotes the integration of physical and behavioral health services at every key stage of service and improves overall integration and coordination of medical, behavioral, and psychosocial supports. We will work with medical case managers to ensure the development of culturally-specific, individualized care plans that reflect the member’s strengths and self- identified goals. We help members obtain services and connect them with community-based resources while advocating for the member’s needs, desires, and rights.
We endorse a chronic care model that provides an evidence-based framework to increase the quality of care, reduce costs and improve outcomes for individuals with substance use disorders.

This model incorporates the necessary societal, systemic, and legislative overhaul to promote continuous and real improvements in care and clinical outcomes, and has been successfully employed to treat individuals with various common chronic illnesses, such as diabetes.

7. Continuous Outcome Based Program Improvement

We continually measure and improve our substance use disorder programs by using SAMHSA’s National Outcome Measures (NOMs) performance targets that measures real-life progress for members undergoing addiction treatment. Measurements includes targets such as abstinence from drugs, abstinence from alcohol, and member social connectedness. Beacon also uses health risk assessments, surveys, and call/outreach statistics to continually inform and improve the care management program.

Putting Our Best Practices to Work: Beacon’s National Substance Use Disorder Program Experience


Since 2007, we have administered substance use disorder treatment services for non-Medicaid members funded by Kansas’ Substance Abuse Prevention and Treatment (SAPT) block grants. Overseeing integration of both state and federal funds for substance use treatment for adolescents, adults and families, we coordinate a complete and effective network of private and community-based substance use disorder treatment services.
Since 2009, we have also administered the Kansas Driving Under the Influence (DUI) program, a jail diversion program where non-violent offenders who have been convicted of their third or subsequent DUI charge receive medically necessary substance use disorder treatment.

Our substance use disorder program operates on the Recovery-Oriented System of Care (ROSC) approach to substance use disorder treatment and services, supporting a person-centered approach to recovery. Through our ROSC initiative, we improved member outcomes through a variety of services and programs, including:

  • Person-centered case management
  • Peer recovery services, including development of curriculum for potential peer staff
  • Transportation services to help obtain wraparound services
  • Overnight boarding services for women with children
  • Encouraging providers to utilize recovery-oriented services such as Crisis Intervention and Alcoholics Anonymous meetings

To ensure that individuals have immediate access to appropriate treatment, we operate a 24/7 toll-free hotline for immediate support for screening and referral for substance use concerns. We also developed and conducted a pilot project for Medication Assisted Treatment, negotiating a reduced cost for Vivitrol to distribute medications across the state, and recruited and contracted with several labs to provide the required initial and periodic laboratory and biometric testing.

Outcome Data

From 2008 to 2015, we achieved significant results and cost savings:

  • Doubled the number of individuals gaining access to substance use disorder treatment while experiencing annual reductions in funding
  • Decreased overall higher level of care average length of stay by almost 16%:
    • Reintegration: 12% reduction in ALOS
    • Intermediate Adolescent: 25% reduction in ALOS
    • Social Detox: 30% reduction in ALOS
  • Cumulative improvement in NOMS for 2015:
    • Increased members’ social connectedness to their home environment: 1,595%
    • Abstinence from drugs: 998%
    • Abstinence from alcohol: 965%


For 15 years, Value Behavioral Health of Pennsylvania, a Beacon Health Options company, has managed substance use disorder services for HealthChoices, Pennsylvania’s county-based Medicaid program. Our substance use and support services make a significant impact in these counties, where low income and rural environments limits access to services for many citizens.

We serve each of our Pennsylvania clients individually, designing responsive, unique programs to meet the specific needs of each county’s staff, members, individuals in recovery, families and providers. Here are some of the services we provide:

  • Our Intensive Care Managers specialize in coordinating care for members with complex substance use conditions, emphasizing care coordination with the member’s Physical Health MCO, with the goal of decreasing consumer hospitalizations and increasing community tenure.
  • Our Peer Specialists and Drug & Alcohol Recovery Specialists provide critical education and problem-solving skills, helping members transition back into the community.
  • We provide training to law enforcement, teachers, and juvenile justice works to recognize the signs and symptoms of substance use disorders, as well as referral protocols.
  • Due to a high and growing rate of opiate and heroin use, we work with counties to evaluate the provider network to support the work of PCPs, and encourage the use of community support programs (i.e., recovery coaching, peer support, housing, and employment support) to ensure a chronic care model is readily available.

Outcome Data

  • Overall 96% satisfaction of consumers and families with services they received
  • In Greene County, the percent of HealthChoices members who have used mental health and/or substance abuse services has increased by more than 61 percent from 2003 through 2012


As the administrative services organization (ASO) for the Maryland Department of Health and Mental Hygiene/Mental Hygiene Administration, we deliver cost effective, recovery-oriented care for 1.1 million Medicaid and eligible uninsured consumers.

To drive engagement, our community-based staff partners with providers and community support programs where our members live, and we offer PCP training and practice supports through:

  • Screening, Brief Intervention and Referral to Treatment (SBIRT)
  • Promoting Early Detection and Screening of Alcohol Used by Youths
  • Alcohol Prevention and Screening During Pregnancy

To ensure services are accessible, we offer community health works and lay health educators of specific cultural backgrounds to provide a “cultural bridge.” Our eld-based Care Managers are continually in the community to engage individuals face-to-face, and we assist with any transportation barriers (such as providing Metro cards) and provide translation services when needed.

We are committed to a person-centered, recovery-oriented approach that actively involves individuals with lived substance use disorder experience, and employ Peer Specialists as well as contract with local peer-run agencies. Our Peer Specialists have worked with over 1,200 members.

Outcome Data

  • Increased the number of people served while decreasing the average cost per member
  • Aligned cost of care with best practices, resulting in an annualized savings of $4.1 million
  • Consumers reported 94% satisfaction rating with care management staff


Since 1996, Massachusetts Behavioral Health Partnership (MBHP), a Beacon Health Options company, has maintained a comprehensive community- based provider network offering a full continuum of acute and post-acute substance use treatment services across the Commonwealth. We currently have contracts with the entire substance use disorder treatment provider community serving the Medicaid population.

Using a Central Navigation System (CNS), we provide information and support for members seeking information about substance use treatment, and help them take full advantage of their substance use bene ts, as well as connect them to community-based services and groups that provide added support. Our team is focused on ensuring individuals receive services in the most appropriate setting to increase engagement in the recovery process. Some of these services include:

  • Intensive Care Coordination
  • Emergency Services Program/Mobile Crisis Intervention (ESP/MCI)
  • Outpatient Substance Use Disorder Services
    • SOAP
    • Ambulatory Detoxi cation
    • Acupuncture Treatment
  • Diversionary Services
    • Acute Treatment Services (ATS) for Substance Use Disorders
    • Enhanced Acute Treatment Services (E-ATS) for Individuals with Co-occurring Mental Health and Substance Use Disorders
    • Clinical Stabilization Services (CSS) for Substance Use Disorders
  • Inpatient Substance Use Disorder Services (Level IV Detoxification Services)

Focus on Opioid Treatment and Prevention

Opioid addiction is an urgent problem in the Commonwealth that involves multiple systemic issues and requires effective long-term solutions in addiction treatment and psychosocial rehabilitation. We are executing a wide range of pilots and programs in Massachusetts to address the rising opioid epidemic. They include:

  • The Changing Pathways project, which helps improve member transitions from inpatient withdrawal management programs to outpatient Medication-Assisted Treatment (MAT).
  • Community Support Programs to promote adherence to MAT, ensure care continuity for members discharged from withdrawal management programs, and improve follow up appointment rates.
  • Intensive Care Management for Methadone Maintenance program where Beacon partners with methadone treatment providers and leverages intensive case management to help improve methadone maintenance adherence. Improved adherence has been shown to reduce inpatient readmissions and mortality for these members.

Forearm Exercises to Build Strength and Reduce Wrist + Elbow Strain

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Treatment options for tennis elbow

Tennis elbow is a painful condition that usually comes from overuse or repetitive use of the muscles and tendons of the forearm and the elbow joint.

Several layers of treatment can be implemented at home or after consulting a physician.

First, rest is important. The rest allows the tiny tears in the tendon attachment to heal. Tennis players treat more serious cases with ice, anti-inflammatory drugs, soft tissue massage, stretching exercises, and ultrasound therapy.

[man with tennis elbow]
Racquet sports and other activities that put strain on the forearm can cause tennis elbow.

Stretches and progressive strengthening exercises involving use of weights or elastic bands to increase pain-free grip strength and forearm strength can be helpful.

Physiotherapists commonly advise racquet sports players to strengthen their shoulder rotator cuff, scapulothoracic, and abdominal muscles. This can help to reduce overcompensation in the wrist extensors during gross shoulder and arm movements.

Soft tissue release or massage can help to reduce muscular tightness and decrease the tension on the tendons. Strapping the forearm can help realign the muscle fibers and redistribute the load. A physician may recommend immobilizing the forearm and elbow by using a splint for 2 to 3 weeks.

If symptoms are very painful, and the condition is making movement difficult, a steroid injection may be recommended.

Cortisone is a steroid that can help to reduce inflammation. After a steroid injection, the person should rest the arm and avoid putting too much strain on it too quickly.

Ice massage and muscle stimulating techniques can help the muscles to heal.

Other treatments include injections of botulinum toxin, also known as Botox and extra-corporeal shock wave therapy, a technique that is thought to trigger healing by sending sound waves to the elbow. Heat therapy, low level laser therapy, occupational therapy, and trigger point therapy are other options.

A new type of therapy is an injection of platelet-rich plasma (PRP), prepared from the patient’s own blood. PRP contains proteins that encourage healing. The American Academy of Orthopaedic Surgeons (AAOS) describe this treatment as promising but still under investigation.

Between 80 percent and 95 percent of patients recover without surgery, but in the rare cases where nonsurgical treatment does not solve the problem in 6 to 12 months, surgery may be needed to remove the damaged part of the tendon and relieve the pain.

In a discussion published in the Canadian Family Physician, Finestone and Rabinovitch, refer to a number of exercises using dumbbells that have helped with muscle conditioning in patients with tennis elbow. They point out that the patient should “be compliant and have some tolerance for pain.”

Forearm Supports Reduce Upper Body Pain Linked To Computer Use

Providing forearm support is an effective intervention to prevent musculoskeletal disorders of the upper body and aids in reducing upper body pain associated with computer work, according to a study in The British Journal of Occupational and Environmental Medicine.

Reported in the April issue, the study shows that use of large arm boards significantly reduces neck and shoulder pain as well as hand, wrist and forearm pain. “Based on these outcomes, employers should consider providing employees who use computers with appropriate forearm support,” said lead author David Rempel, MD, MPH, director of the ergonomics program at San Francisco General Hospital and professor of medicine at the University of California, San Francisco.

Study findings also show arm boards and ergonomics training provide the most protective effect, with a statistically significant reduction in both neck and shoulder pain and right hand/wrist/forearm pain in comparison to the control group, who did not receive forearm support. The boards reduced the risk of incidence of neck and shoulder disorders by nearly half.

According to the authors, musculoskeletal disorders of the neck, shoulders and arms are a common occupational health problem for individuals involved in computer-based customer service work. Specific disorders include wrist tendonitis, elbow tendonitis and muscle strain of the neck and upper back. These health problems account for a majority of lost work time in call centers and other computer-based jobs. “Extended hours of mouse or keyboard use and sustained awkward postures, such as wrist extension, are the most consistently observed risk factors for musculoskeletal disorders,” Rempel added.

The one year, randomized study evaluated the effects of two workstation interventions on the musculoskeletal health of call center employees — a padded forearm support and a trackball. The forearm support is commonly called an arm board and attaches to the top front edge of the work surface. The trackball replaces a computer mouse and uses a large ball for cursor motion.

The researchers tested employees from two customer service center sites of a large health maintenance organization. Employees had to perform computer based customer service work for a minimum of 20 hours per week in order to qualify for the study. For one year, 182 participants filled out a weekly questionnaire to assess pain level in their hands, wrists, arms, upper backs and shoulders.

Participants were randomized into four groups, each receiving a different intervention: ergonomics training, training plus a trackball, training plus forearm support, or training with both a trackball and forearm support. Outcome measures included weekly pain severity scores and diagnosis of a new musculoskeletal disorder in the upper extremities or the neck-shoulder region based on physical examination performed by a physician.

The trackball intervention had no effect on right upper extremity disorders. “The trackball was difficult for some participants to use,” said Rempel. “Employees with hand pain may want to try them, but they should stop if it is difficult to use.”

The researchers also performed a return-on-investment calculation for the study to estimate the effects of ergonomic interventions on productivity and costs. Their calculations predicted a full return of armboard costs for employers within 10.6 months of purchase.

“Based on this study, it is in the best interest of the company and the employees to provide forearm supports and training,” Rempel concluded.

In the study, the authors also outline other ergonomic-specific tasks that employees who use computers can do to relieve pain on their own. They suggest employees take scheduled breaks, maintain an erect posture, adjust chair height so thighs are parallel to the floor, adjust arm support and work surface height so the forearms are parallel to the floor, adjust the mouse and keyboard location to minimize the reach, and adjust monitor height so that the center of the monitor is approximately 15 degrees below the visual horizon.


Co-authors of the study include Niklas Krause, MD, PhD; Robert Goldberg, MD; Mark Hudes, PhD; and Gary Urbiel Goldner, MS, from the division of occupational and environmental medicine, UCSF; and Douglas Benner, MD, occupational health, Kaiser Permanente of Northern California.

Infertility and Its Treatments in Association with Autism Spectrum Disorders: A Review and Results from the CHARGE Study

Previous findings on relationships between infertility, infertility therapies, and autism spectrum disorders (ASD) have been inconsistent. The goals of this study are first, to briefly review this evidence and second, to examine infertility and its treatments in association with having a child with ASD in newly analyzed data. In review, we identified 14 studies published as of May 2013 investigating infertility and/or its treatments and ASD. Overall, prior results showed little support for a strong association, though some increases in risk with specific treatments were found; many limitations were noted. In new analyses of the CHildhood Autism Risk from Genetics and the Environment (CHARGE) population-based study, cases with autism spectrum disorder (ASD, n = 513) and controls confirmed to have typical development (n = 388) were compared with regard to frequencies of infertility diagnoses and treatments overall and by type. Infertility diagnoses and treatments were also grouped to explore potential underlying pathways. Logistic regression was used to obtain crude and adjusted odds ratios overall and, in secondary analyses, stratified by maternal age (≥35 years) and diagnostic subgroups. No differences in infertility, infertility treatments, or hypothesized underlying pathways were found between cases and controls in crude or adjusted analyses. Numbers were small for rarer therapies and in subgroup analyses; thus the potential for modest associations in specific subsets cannot be ruled out. However, converging evidence from this and other studies suggests that assisted reproductive technology is not a strong independent risk factor for ASD.

These analyses included 537 ASD cases and 381 TD controls. Parents of children with an ASD were slightly older than TD control parents, and case mothers were slightly more likely to have had a history of smoking; other demographic and lifestyle factors were similar between the groups (Table 2).

Table 2

Basic characteristics of the study population (n = 918).

Nine percent of both ASD cases and TD controls had used at least one type of infertility treatment for the index birth. Numbers were small for rarer types of therapies, but overall, frequencies were remarkably similar between the ASD and TD groups (Table 3). The ASD case group also did not differ from TD controls by infertility diagnosis or according to hypothesized pathways.

Table 3

Infertility and infertility treatments by case status.

In adjusted analyses comparing ASD cases to TD controls, fertility therapies and infertility continued to show no association with odds of ASD (Table 4). Overall, odds ratios were all close to 1 (OR for overall infertility treatment use = 1.16, 95% CI 0.70, 1.93), though for certain therapies, confidence intervals were imprecise due to small numbers. In particular, any male treatment had only nine exposed cases in the primary analysis, and while similar point estimates were similarly elevated across subgroup analyses for this treatment type (OR approaching 2), these results were not significant. Contrary to our hypotheses, no differences were noted according to hypothesized underlying pathways (Appendix, Table S1). Results were similar across models tested, including in weighted (Model 3, Table 4) and unweighted (Model 2, Table 4) analyses, and did not materially change when using reduced models including only maternal age, child year of birth, and matching factors, or conversely, when considering further adjustment for pre-pregnancy smoking and BMI, which have been associated with both the exposures and outcome under study in some investigations [30,34,35,36].

Table 4

Odds of ASD according to infertility and treatments.

In subgroup analyses among mothers of advanced age (n = 237) and by diagnostic subgroup (367 autistic disorder and 170 broader ASD), results were very similar, and again non-significant for any associations with infertility and infertility treatments (data not shown; OR for any infertility treatment in the advanced maternal age group: 1.20, 95% CI 0.56, 2.59; in the autistic disorder case group, the corresponding OR was 1.27, 95% CI 0.73, 2.20). However, it should be noted that numbers were small within these groups; only 27 cases used any fertility therapies among the advanced maternal age subgroup, with numbers for individual types of therapies around 10 or fewer. Likewise, sensitivity analyses utilizing only self-reported information, or only information from medical records, also did not demonstrate any significant associations.


The results of this case-control study do not provide evidence for an association between fertility therapies and autism spectrum disorders. We examined a number of different types of therapies and conditions underlying the infertility being treated, and overall found remarkable similarity between ASD cases and typically developing controls. However, due to the low power to detect subtler effects in our study, we cannot exclude the potential for modest associations with rarer therapies or conditions. These topics should therefore be further explored in very large studies with standardized outcome ascertainment and rigorous exposure information.

A major strength of this study, and an improvement over a number of prior studies examining infertility and/or its treatments in association with ASD, is the confirmation of both case status and exposures through rigorous, gold standard measures. All children included in these analyses were evaluated at the UC Davis MIND Institute for diagnostic confirmation, and detailed interviews were conducted and medical records abstracted (in the majority of the study group) for exposure information. In contrast, none of the prior studies examining these factors have confirmed case and comparison group status at this level of detail. We also had information on a full range of infertility diagnoses and treatments, which is lacking in other studies. Our estimates of frequency of use of a wide range of therapies according to ASD status thus fill a needed gap in the literature. Despite using retrospective reporting, as had been previously utilized in a number of prior investigations, we also collected medical records in a large majority of the group for confirmation. We also carried out a thorough confounder identification strategy, whereas many of the prior studies of infertility treatments and ASD failed to adjust for even basic sociodemographic risk factors [16,20,21,22,25,27]. We further took advantage of the linkage of all our cases and controls to the population birth files that included all non-participants in order to account for potential differential participation (selection bias) through weighted analyses, which has not been done in previous case-control studies of this topic.

However, a number of limitations in our work should be noted. Despite a sample size of nearly 1,000 mother-child pairs, our study was limited by the relatively rare exposures, leading to small numbers in many categories. Thus, while we had sufficient power to detect odds ratios of at least 1.75 for treatments and diagnoses with prevalence over 5%, power was reduced to detect associations for specific therapy types with infrequent use. To date, only Hvitjorn and colleagues [17] have had adequate numbers to examine rarer therapies, but unfortunately, they did not have information on many different types of treatments. We cannot rule out bias due to participation, a common problem in case-control studies, by demographic factors that could be related to the exposures studied here; however, our use of sampling weights strove to mitigate any such biases. While we did rely on retrospective reporting, between 70–80% of our exposures were confirmed in medical records. Another potential limitation, not restricted to our own study, is the definition of infertility itself; how different couples perceive “regular intercourse” is open to interpretation, and timing, diet, lifestyle and cultural factors all may influence reported infertility in ways not related to hypothesized biological pathways.

Consistent with our results, the majority of prior work suggests that use of assisted technologies does not increase risk of adverse child outcomes (with the notable exceptions of multiple births, pre-term birth and low-birth weight). A handful of studies have suggested increased risks of autism, or developmental delay, cerebral palsy, and imprinting disorders with use of ART [15,19,22]. However, our study and four other investigations [17,18,25,27], including the largest study of ASD and assisted conception to date, with over 3,600 cases and approximately 33,000 children exposed to assisted conception [17], found no association between ART and risk of ASD specifically. We also did not see associations with IVF or other ART subtypes, though numbers were small. Two prior studies have also found no association between ASD and IVF or ICSI [25,26], while results from few others have been inconsistent for more broadly defined developmental outcomes and ART subtypes [19,22,24,27].

For other types of infertility treatments, there is limited information on associations with ASD specifically. A handful of prior studies have suggested associations with ovulation drugs or medications (three studies, each of which found associations only in different subgroup analyses) [17,18,28], specific hormones (two studies) [17,28], and artificial insemination/intrauterine insemination (two studies) [18,28]. Specifically, an investigation in the Nurses’ Health Study II found a significant association between ASD and OID in an advanced maternal age subgroup [18], which was a larger subgroup than the current study; thus, smaller numbers here could account for the differences seen. The Danish study conducted by Hvitjorn and colleagues [17] found significant associations with ASD for female offspring exposed to OID as well as for use of follicle-stimulating hormone (FSH)-containing medications, while another study saw an association with urofillitropin, a purified form of FSH, only among multiple births [28]. Given that FSH-containing medications are indicated for a range of underlying problems, the meaning of these findings is not immediately evident. We did not see an association with FSH specifically, and a larger investigation than ours will be needed to replicate results. Another recent study found no association with a general category of infertility medications (that included OID) and ASD among singleton births [28], but did find a significant association among multiple births. Our results did not differ in multiple or singleton births, though as in the work by Grether and colleagues, exposed numbers among multiples were small, thereby limiting conclusions.

The Nurses’ investigation also saw an association with AI, which the CHARGE study did not replicate; however, the source of infertility treatment information in the Nurses’ study was not as rigorous as in the current study. We did find increased odds ratios for male treatments in our study; though non-significant, use of AI is sometimes indicated for male factors. Again, Grether and colleagues’ study found an association with IUI and ASD only among multiple births but not in singletons, providing mixed results. Given that Hvitjorn and colleagues’ definition of OID included use with and without AI, future studies should also investigate AI in association with ASD, both in singleton and multiple births.

Our analyses of these infertility treatments considered adjustment for a number of potential confounders. Prior studies examining potential effects of infertility treatments have adjusted for or stratified on multiple births in attempt to assess the effect of the treatments on the various outcomes studied, not mediated by multiplicity. For comparison to this work, we examined exposures stratified by singleton and multiple births and found that results did not differ (data not shown; nor did results materially change when adjusting for birth order, which has similar issues when considering effects of infertility and its treatments). However, conditioning on a downstream consequence of exposure can introduce bias. Another example is adjustment for birth weight, a common flaw in studies of prenatal exposures; again, we did not include birth weight in our multivariable models for this reason. Future large studies may benefit from the use of more sophisticated statistical methods, such as marginal structural models (MSMs) [37,38], to determine controlled direct effects not mediated by these factors. Alternatively, using mediator analyses [39,40] may also be useful in determining the impact of factors that may be downstream of infertility therapies, assuming confounding of the intermediate-outcome association is adequately accounted for. Given the null findings for exposures in our study, we did not see significant associations with potential mediators when we conducted such analyses (results provided in Appendix, Table S2); however, pregnancy complications, low birth weight, and multiple births had fairly large estimates of percent mediation. Little prior work has investigated underlying infertility, rather than just its treatments, in association with ASD. While two small studies reported increased prevalence of infertility among mothers of affected children [16,21], and a third study reported an association only for multiple births [28], two larger studies (one registry-based and one nested case-control) have not found associations between maternal infertility and risk of ASD [17,18]; our work is consistent with these recent findings.

Infertility treatments have been hypothesized to influence ASD through a number of mechanisms, including hormonal influences of the medications, effects of invasive procedures on DNA methylation or other direct effects of the procedure/treatment, impaired egg quality, influences of the underlying infertility, or simply through associations with downstream consequences of the treatment (such as multiple birth, pregnancy complications, low birth weight, or pre-term birth) [15,18,41]. While we had hypothesized that hormonal or inflammatory pathways may be involved, we did not see associations with these pathways as related to infertility and its treatments. However, power was limited to detect modest associations (i.e., those on the order of OR = 1.5 or less), given the number of exposed cases in each of the pathway groups. Continued investigation of such pathways and groupings as conducted here may be useful in learning more about potential underlying mechanisms.


Our work and that of others highlights the need for very large studies in order to fully address the topic of infertility and its treatments in association with ASD. Overall, the evidence to date suggests that women using infertility therapies do not need to be concerned about strong increases in risk of ASD. However, the known risks associated with infertility therapies, such as prematurity, low birth weight infants and multiple births, remain as concerns associated with use of these therapies, and evidence suggests the need for continued long-term follow-up of children conceived using these procedures [14]. Women using these therapies appear to also be at higher risk for pregnancy complications, although this increased risk could be a result of the primary infertility and its root causes. Thus, further investigations are needed to disentangle the complex role of underlying infertility, its treatments, and possible mediators of hypothesized effects on risk of ASD. The limited power to detect modest associations in our study suggests further work may be required to (a) detect subtler risks associated with specific infertility therapies and underlying infertility pathways, and (b) better understand associations in groups such as multiple births and women with advanced maternal age, for whom these treatments and issues are more common.

Highest Average Expenses for Common Conditions

AHRQ Stats: Highest Average Expenses for Common Conditions

For the nine most commonly treated conditions among U.S. adults in 2013, the highest average expenses per person were for the treatment of heart conditions ($3,794 per person), trauma-related disorders ($3,070) and diabetes ($2,565). (Source: AHRQ, Medical Expenditure Panel Survey Statistical Brief #487: Expenditures for Commonly Treated Conditions among Adults Age 18 and Older in the U.S. Civilian Noninstitutionalized Population, 2013.)

Today’s Headlines:

Increased Physical Activity for Kids Would Have Health and Economic Benefits

If half of U.S. children 8 to 11 years old got the recommended amount of physical activity, the proportion of children who are overweight or obese would decrease by 4 percent, according to new research funded partially by AHRQ. This would save $8 billion in annual medical costs associated with obesity-related conditions, researchers concluded. Having this same 50 percent of kids receive the recommended amount of exercise would also avert approximately $14 billion in annual lost productivity costs over their lifetimes, researchers concluded. The article in the May issue of Health Affairs estimated that only 32 percent of children currently get recommended amount of exercise, which consists of 25 minutes of high-calorie-burning physical activity three times a week. The study authors concluded that increasing children’s physical activity should be a higher national priority, in part because possible savings substantially outweigh the costs of interventions promoting increased physical activity. Access the abstract.

Highlights From AHRQ’s Patient Safety Network

AHRQ’s Patient Safety Network (PSNet) highlights journal articles, books and tools related to patient safety. Articles featured this week include:

Review additional new publications in PSNet’s current issue or access recent cases and commentaries in AHRQ’s WebM&M (Morbidity and Mortality Rounds on the Web).

Nearly 6 of 10 Hospital-Based Surgeries in 2014 Occurred in Outpatient Settings

In 2014, 58 percent of the nation’s 17.2 million hospital-based surgical visits took place in outpatient settings, according to a new AHRQ statistical brief. The report from AHRQ’s Healthcare Cost and Utilization Project helps to quantify ongoing shifts toward more outpatient and fewer inpatient hospital-based surgical procedures. Among the most common outpatient surgeries in 2014 were lens and cataract procedures (nearly 100 percent performed in outpatient settings), cartilage removal in the knee (99 percent), tonsillectomy (96 percent), peripheral nerve decompression (95 percent), and hernia repair (92 percent). Private insurance was the most common payer for ambulatory surgery visits, while Medicare was the most common payer among inpatient surgical stays. For more data on inpatient and outpatient hospital-based surgery trends, access the statistical brief.

Study Questions Whether High-Priced Providers Deliver Higher-Quality Care

Patients who received care at higher-priced physician practices rated those practices higher than their lower-priced counterparts on measures of care coordination and management, according to an AHRQ-funded article published in the May issue of Health Affairs. However, patients’ evaluations were similar on overall care and services such as mammography, vaccinations or diabetes treatment, no matter the price, the research found. Authors defined higher-priced practices as those that charged 36 percent higher than lower-priced practices—on average about $84 for an office visit for a medium-complexity patient for higher-priced practices versus about $62 for the same type of patient visit at a lower-priced practice. The authors concluded that the findings suggest a weak relationship between practices’ prices and the quality and efficiency of care they provide. This research was funded by AHRQ’s Comparative Health System Performance Initiative, which studies how health care delivery systems promote evidence-based practices and patient-centered outcomes research in delivering care. Access the abstract.