Measuring disease progression in early Parkinson disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) experience
Sotirios A Parashos, Sheng Luo, Kevin M Biglan, Ivan Bodis-Wollner, Bo He, Grace S Liang, G Webster Ross, Barbara C Tilley, Lisa M Shulman, NET-PD Investigators, Cynthia R Gross, T Chen, David E Levy, Robert L Rodnitzky, K Michael Welch, M Flint Beal, Jeffrey L Cummings, David Geffen, Stanley Fahn, Bruce Levin, Russell G Katz, Deborah B Marin, C Warren Olanow, Jeffrey C Martin, William McDonald, Diane Murphy, Steven Piantadosi, William J Powers, Leon J Thal, Alison Wichman, John Marler, Joanne Odenkirchen, Bernard Ravina, Karl Kieburtz, Barbara Tilley, Kathleen Shannon, Caroline Tanner, Patricia Deppen, Richard B Dewey Jr, Brigid Hayward, Burton Scott, Joanne Field, Matthew Brodsky, Pamela Andrews, Bala Manyam, Jacqueline Whetteckey, Jayaraman Rao, Maureen Cook, Michael J Aminoff, Chadwick Christine, Jessie Roth, Sotirios Parashos, Kathleen Shannon, Jeana Jaglin, Carlos Singer, Marian A Perez, Anita Blenke, Robert Hauser, Becky Dunlop, Kelly Lyons, Amy Parsons, Maureen Leehey, Lisa Shulman, Katharine Pabst, Rodger Elble, Charlene Young, Kapil Sethi, Wayne Martin, Germaine McInnes, Vincent P Calabrese, Peggy Roberge, Robert Hamill, Clare Homan, Ivan G Bodis-Wollner, Elizabeth Hayes, Webster G Ross, Stephanie Terashita, Joel Trugman, Margaret F Keller, Jacob I Sage, Debbie Caputo, Dorothy Shearon, Tammie Kelsey, Andrew Feigin, Ray L Watts, Natividad Stover, Rebecca McMurray, Sue Reichwein, David Simon, Daniel Tarsy, Lisa Scollins, Ron Tintner, Christine Hunter, Maryan DeAngelis, Richard S Burns, Holly Shill, Jill Danielson, Lynn Marlor, Charles Adler, Marlene Lind, Jay Gorell, Shana Krstevska, Jay Schneider, Stephen Gollomp, Thomas Jefferson, David Coffey, Mark F Lew, Connie Kawai, Margaret Turk, James Bower, Joseph Handler, Kathleen Greenbaum, Marwan Sabbagh, Zoran Obradov, Peng Huang, Yuko Palesch, Cornelia Kamp, Aileen Shinaman, Debbie Johnsen, Alicia Brocht, Christopher Goetz, Susan Fagan, Cynthia R Gross, Donna T Chen, David E Levy, Karen Marder, Robert L Rodnitzky, K Michael Welch, M Flint Beal, Stanley Fahn, Bruce Levin, Russell G Katz, Deborah B Marin, C Warren Olanow, Jeffrey C Martin, Diane Murphy, William J Powers, Leon J Thal, Alison Wichman, John Marler, Joanne Odenkirchen, Cliff Shults, Karl Kieburtz, Bernard Ravina, Wendy R Galpern, Barbara Tilley, Kathleen Shannon, Caroline Tanner, G Frederick Wooten, Jacob I Sage, Emily Kosa, Ray L Watts, Natividad R Stover, Rebecca McMurray, Mark F Lew, Connie Kawai, David Coffey, Pauline LeBlanc, Matthew Brodsky, Pamela Andrews, Andrew Siderowf, Lisa Shulman, William J Weiner, Katharine Pabst, Jeana Jaglin, Oksana Suchowersky, Lorelei Derwent, Jayaraman Rao, Maureen Cook, Michael J Aminoff, Chad Christine, Jessie Roth, Maureen Leehey, G Webster Ross, Stephanie Terashita, Marian A Perez, Anita Blenke, Brad Racette, Patricia Deppen, Rodger Elble, Charlene Young, Tracy Stewart, Kapil Sethi, John Taylor, Peggy Roberge, Richard B Dewey Jr, Brigid Hayward, Joseph Jankovic, Christine Hunter, Margaret F Keller, Danna Jennings, Tammie Kelsey, Wayne Martin, Joseph Savitt, Becky Dunlop, Rajesh Pahwa, Kelly E Lyons, Amy Parsons, John Fang, Dorothy Shearon, Andrew Feigin, Margaret Marie, Charles Adler, Marlene Lind, Burton Scott, Joanne Field, Martha Nance, Susan Peterson, Richard S Burns, Lynn Marlor, Ivan Bodis-Wollner, Elizabeth Hayes, Stephanie Sendek, Stephen Gollomp, Gwyn Vernon, Thomas Jefferson, Peter LeWitt, Maryan DeAngelis, Linda Paul, Jay Gorell, Shana Krstevska, Marilyn Flewellen, Sharon McCarthy, Ryan Uitti, Margaret Turk, James Bower, Marwan Sabbagh, Zoran Obradov, Jorge Juncos, Mary Louise Musante, Hubert Fernandez, Gordon Brown, Peng Huang, Cornelia Kamp, Aileen Shinaman, Alicia Brocht, Susan Bennett, Debbie Baker, Christopher Goetz, Susan Fagan, Patrick Mauldin, Sotirios A Parashos, Sheng Luo, Kevin M Biglan, Ivan Bodis-Wollner, Bo He, Grace S Liang, G Webster Ross, Barbara C Tilley, Lisa M Shulman, NET-PD Investigators, Cynthia R Gross, T Chen, David E Levy, Robert L Rodnitzky, K Michael Welch, M Flint Beal, Jeffrey L Cummings, David Geffen, Stanley Fahn, Bruce Levin, Russell G Katz, Deborah B Marin, C Warren Olanow, Jeffrey C Martin, William McDonald, Diane Murphy, Steven Piantadosi, William J Powers, Leon J Thal, Alison Wichman, John Marler, Joanne Odenkirchen, Bernard Ravina, Karl Kieburtz, Barbara Tilley, Kathleen Shannon, Caroline Tanner, Patricia Deppen, Richard B Dewey Jr, Brigid Hayward, Burton Scott, Joanne Field, Matthew Brodsky, Pamela Andrews, Bala Manyam, Jacqueline Whetteckey, Jayaraman Rao, Maureen Cook, Michael J Aminoff, Chadwick Christine, Jessie Roth, Sotirios Parashos, Kathleen Shannon, Jeana Jaglin, Carlos Singer, Marian A Perez, Anita Blenke, Robert Hauser, Becky Dunlop, Kelly Lyons, Amy Parsons, Maureen Leehey, Lisa Shulman, Katharine Pabst, Rodger Elble, Charlene Young, Kapil Sethi, Wayne Martin, Germaine McInnes, Vincent P Calabrese, Peggy Roberge, Robert Hamill, Clare Homan, Ivan G Bodis-Wollner, Elizabeth Hayes, Webster G Ross, Stephanie Terashita, Joel Trugman, Margaret F Keller, Jacob I Sage, Debbie Caputo, Dorothy Shearon, Tammie Kelsey, Andrew Feigin, Ray L Watts, Natividad Stover, Rebecca McMurray, Sue Reichwein, David Simon, Daniel Tarsy, Lisa Scollins, Ron Tintner, Christine Hunter, Maryan DeAngelis, Richard S Burns, Holly Shill, Jill Danielson, Lynn Marlor, Charles Adler, Marlene Lind, Jay Gorell, Shana Krstevska, Jay Schneider, Stephen Gollomp, Thomas Jefferson, David Coffey, Mark F Lew, Connie Kawai, Margaret Turk, James Bower, Joseph Handler, Kathleen Greenbaum, Marwan Sabbagh, Zoran Obradov, Peng Huang, Yuko Palesch, Cornelia Kamp, Aileen Shinaman, Debbie Johnsen, Alicia Brocht, Christopher Goetz, Susan Fagan, Cynthia R Gross, Donna T Chen, David E Levy, Karen Marder, Robert L Rodnitzky, K Michael Welch, M Flint Beal, Stanley Fahn, Bruce Levin, Russell G Katz, Deborah B Marin, C Warren Olanow, Jeffrey C Martin, Diane Murphy, William J Powers, Leon J Thal, Alison Wichman, John Marler, Joanne Odenkirchen, Cliff Shults, Karl Kieburtz, Bernard Ravina, Wendy R Galpern, Barbara Tilley, Kathleen Shannon, Caroline Tanner, G Frederick Wooten, Jacob I Sage, Emily Kosa, Ray L Watts, Natividad R Stover, Rebecca McMurray, Mark F Lew, Connie Kawai, David Coffey, Pauline LeBlanc, Matthew Brodsky, Pamela Andrews, Andrew Siderowf, Lisa Shulman, William J Weiner, Katharine Pabst, Jeana Jaglin, Oksana Suchowersky, Lorelei Derwent, Jayaraman Rao, Maureen Cook, Michael J Aminoff, Chad Christine, Jessie Roth, Maureen Leehey, G Webster Ross, Stephanie Terashita, Marian A Perez, Anita Blenke, Brad Racette, Patricia Deppen, Rodger Elble, Charlene Young, Tracy Stewart, Kapil Sethi, John Taylor, Peggy Roberge, Richard B Dewey Jr, Brigid Hayward, Joseph Jankovic, Christine Hunter, Margaret F Keller, Danna Jennings, Tammie Kelsey, Wayne Martin, Joseph Savitt, Becky Dunlop, Rajesh Pahwa, Kelly E Lyons, Amy Parsons, John Fang, Dorothy Shearon, Andrew Feigin, Margaret Marie, Charles Adler, Marlene Lind, Burton Scott, Joanne Field, Martha Nance, Susan Peterson, Richard S Burns, Lynn Marlor, Ivan Bodis-Wollner, Elizabeth Hayes, Stephanie Sendek, Stephen Gollomp, Gwyn Vernon, Thomas Jefferson, Peter LeWitt, Maryan DeAngelis, Linda Paul, Jay Gorell, Shana Krstevska, Marilyn Flewellen, Sharon McCarthy, Ryan Uitti, Margaret Turk, James Bower, Marwan Sabbagh, Zoran Obradov, Jorge Juncos, Mary Louise Musante, Hubert Fernandez, Gordon Brown, Peng Huang, Cornelia Kamp, Aileen Shinaman, Alicia Brocht, Susan Bennett, Debbie Baker, Christopher Goetz, Susan Fagan, Patrick Mauldin
Abstract
Importance: Optimizing assessments of rate of progression in Parkinson disease (PD) is important in designing clinical trials, especially of potential disease-modifying agents.
Objective: To examine the value of measures of impairment, disability, and quality of life in assessing progression in early PD.
Design, setting, and participants: Inception cohort analysis of data from 413 patients with early, untreated PD who were enrolled in 2 multicenter, randomized, double-blind clinical trials.
Interventions: Participants were randomly assigned to 1 of 5 treatments (67 received creatine, 66 received minocycline, 71 received coenzyme Q10, 71 received GPI-1485, and 138 received placebo). We assessed the association between the rates of change in measures of impairment, disability, and quality of life and time to initiation of symptomatic treatment.
Main outcomes and measures: Time between baseline assessment and need for the initiation of symptomatic pharmaceutical treatment for PD was the primary indicator of disease progression.
Results: After adjusting for baseline confounding variables with regard to the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score, the UPDRS Part III score, the modified Rankin Scale score, level of education, and treatment group, we assessed the rate of change for the following measurements: the UPDRS Part II score; the UPDRS Part III score; the Schwab and England Independence Scale score (which measures activities of daily living); the Total Functional Capacity scale; the 39-item Parkinson's Disease Questionnaire, summary index, and activities of daily living subscale; and version 2 of the 12-item Short Form Health Survey Physical Summary and Mental Summary. Variables reaching the statistical threshold in univariate analysis were entered into a multivariable Cox proportional hazards model using time to symptomatic treatment as the dependent variable. More rapid change (ie, worsening) in the UPDRS Part II score (hazard ratio, 1.15 [95% CI, 1.08-1.22] for 1 scale unit change per 6 months), the UPDRS Part III score (hazard ratio, 1.09 [95% CI, 1.06-1.13] for 1 scale unit change per 6 months), and the Schwab and England Independence Scale score (hazard ratio, 1.29 [95% CI, 1.12-1.48] for 5 percentage point change per 6 months) was associated with earlier need for symptomatic therapy.
Conclusions: AND RELEVANCE In early PD, the UPDRS Part II score and Part III score and the Schwab and England Independence Scale score can be used to measure disease progression, whereas the 39-item Parkinson's Disease Questionnaire and summary index, Total Functional Capacity scale, and the 12-item Short Form Health Survey Physical Summary and Mental Summary are not sensitive to change.
Trial registration: clinicaltrials.gov Identifiers: NCT00063193 and NCT00076492.
Source: PubMed